ASCO Education Podcast podcast

Cancer Topics - New Therapies for Lymphoma (Part 2)

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In the second part of this ASCO Education Podcast episode, Dr. Sonali Smith (University of Chicago Medicine) and Dr. Paolo Strati (MD Anderson Cancer Center) discuss the application of new therapies for mantle cell lymphoma and follicular lymphoma through examination of challenging patient cases.

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Air Date: 11/15/21

 

TRANSCRIPT

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SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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SONALI SMITH: Hello, and welcome to part 2 of ASCO Education Podcast on New Therapies for Lymphoma. My name is Dr. Sonali Smith, and I'm a hematologist and medical oncologist specializing in lymphoma and clinical trials for lymphoma. I am also the Elwood V. Jensen professor and chief of the Hematology and Oncology section at the University of Chicago.

PAOLO STRATI: Hello to everybody. I'm Dr. Paolo Strati. I'm a hematologist, and medical oncologist, and assistant professor in the Department of Lymphoma and Myeloma and in the Department of Translational and Molecular Pathology at the University of Texas MD Anderson Cancer Center in Houston, Texas. In part one of this podcast episode, we discuss recently approved therapies for diffuse large B-cell lymphoma. And today, we will be exploring instead new therapies for follicular lymphoma and new therapies for mantle cell lymphoma.

SONALI SMITH: Wonderful. So we are going to start off today with a discussion about a patient case. The individual is a 55-year-old woman with previously untreated follicular lymphoma, low-grade advanced stage, and low tumor burden, and low FLIPI. She was diagnosed three years ago and had observation but more recently developed a 7-centimeter retroperitoneal mass with impending ureteral compression and no PET/C concern for transformation, specifically with an SUVmax of 5.3.

Despite this radiological finding, the patient had a performance status of 0, no symptoms, no significant comorbid health conditions, and was given R-CHOP time six cycles, followed by achievement of a CR. She was then observed, but, unfortunately, 18 months later, the PET/C showed diffuse low FDG-uptake adenopathy, and a lymph-node biopsy was repeated. This showed a follicular-lymphoma relapse.

So Dr. Strati, tell us a little bit about your approach to follicular lymphoma in the initial setting. Do you consider GELF criteria? And how do you select second-line therapy in this patient? Does the early progression of disease within 18 months-- she falls into the category of POD24, or the Progression Of Disease 24 months-- how does this affect your treatment choice going forward?

PAOLO STRATI: Thank you, Dr. Smith. Those are all very good questions. So going to your first question-- we typically use GELF criteria, as you know, developed in France now many years ago, most of the time of initial diagnosis. And that's to determine whether a follicular-lymphoma patient does, indeed, have an indication for treatment.

And this criteria, as you know, are based on lymph node size and number, oragnomegaly, cytopenia. However, it's still debated whether this should also be applied at time of relapse. And in this particular case, the patient, as you said, had what we call a POD24, or progression of disease within 24 months from initiation of chemoimmunotherapy.

Given the suboptimal outcome of these patients, I think that it will not be unreasonable to treat these patients even if they don't formally meet GELF criteria-- so even if they don't have formal indication for treatment at time of relapse. Once the decision is made, standard second-line options for patients with follicular lymphoma currently include chemoimmunotherapy

So if the patient received R-CHOP in frontline, it would be BR. But if they receive BR in frontline, of course, R-CHOP, but also, immunotherapy with R-squared-- so Rituximab, Revlimid-- or lenalidomide, a single-agent anti-CD20 monoclonal antibody, obinutuzumab, which is specifically approved by the FDA in the United States for rituximab-refractory follicular-lymphoma patients, and in very selected cases-- and this is still open for debate-- a high-dose chemo with a platinum-based agent followed by autologous stem-cell transplant.

We don't know at this time what's the ideal second-line strategy for patients like the one that you described in your case-- so a follicular-lymphoma patient with POD24. And to this regard, all are very eagerly awaiting the results of an ongoing SWOG trial, 1608, which is a randomized phase II study comparing in second-line chemoimmunotherapy, immunotherapy, and also, [INAUDIBLE] kinase inhibitor for this patient with POD24.

Finally, one thing which I think is important to consider is that even if R-squared is not currently approved by the FDA in the frontline setting in the United States and, actually, is not approved at all in Canada, in Europe as a frontline treatment, in the United States, it's possible to use it in frontline thanks to existing guidelines. And over the last few years, its frontline use in our country has actually meaningfully increased.

This is creating a new clinical scenario that we never met before. And there are no standard second-line options currently established for these patients, patients who receive frontline R-squared, emphasizing the need of translational research to understand more of the biology of patients who relapse after frontline R-squared but also, emphasizing the need to mostly look into clinical trials when these patients, unfortunately, experience a relapse.

SONALI SMITH: Yes, thank you, Dr. Strati. I agree. I think that it is the way that frontline follicular lymphoma and in the relapsed setting exists is that we have a toolbox and no real clear data on how to personalize the therapy. So your comment about needing some better translational work to fine-tune the clinical trials is really important.

So for this patient, though, she did receive R-squared for 12 cycles and achieved a complete remission after six cycles. 12 months later, a PET/CT showed diffuse, low-level adenopathy, "low level" meaning low uptake on a PET scan. And she had another lymph-node biopsy. This showed persistent follicular lymphoma. So now how do you select your third-line option knowing that we have biologic therapy, as well as cellular therapy, available to this patient?

PAOLO STRATI: So going back to the metaphor that I used before, we have a very nice toolbox, often third-line. But also, in third-line, there's really no strong, robust translational data to drive us when it comes to treatment selection. Agents currently approved by the FDA in the United States as a third-line standard option for patients with relapsed/refractory follicular lymphoma include, as you alluded, [INAUDIBLE] kinase inhibitors, currently three-- copanlisib, duvelisib, and idelalisib, and an EZH2 inhibitor called tazemetostat.

The three [INAUDIBLE] kinase inhibitors currently approved in third line have very similar efficacy with a response rate of 50% and a median progression-free survival of about 10 months. And the selection among the three is typically based on toxicity profile, which is more on the autoimmune side for duvelisib and idelalisib and more on the metabolic side with hyperglycemia and hypertension for copanlisib.

Also, one element that, in my experience, is typically used to select one of these three is the route and the frequency of administration because we have to remember that idelalisib and duvelisib are both given orally twice a day, whereas copanlisib is given intravenously three times a month. And so, of course, different patients may have different preferences.

As a matter of fact, though, the use of [INAUDIBLE] kinase inhibitors for relapsed follicular lymphoma in the United States and I would say, also, in other countries, is quite limited, mostly due to toxicity and relatively limited efficacy. Tazemetostat, the EZH2 H2 inhibitor that I mentioned previously, has a response rate that can vary between 30% and up to 70%, significantly higher in patients who do have a documented EZH2 mutation. But the median progression-free survival is about a year, no matter whether the mutation is present-- so not that different from [INAUDIBLE] kinase inhibitors in the same setting.

Of interest, given the short duration of response, we may consider these agents as a bridging therapy for follicular-lymphoma patients. We [INAUDIBLE] proceed with CAR T-cell therapy because, as you mentioned in your question, CAR T-cell therapy, and specifically, Axi-cel, has been recently approved by the FDA as a third-line option for patients with relapsed/refractory follicular lymphoma based on results from the ZUMA-5 study.

It's important, however, to emphasize that Axi-cel has shown better efficacy and safety data in follicular-lymphoma patients as compared to large B-cell lymphoma patients than we discussed in the previous episode of this podcast. And, as such, Axi-cel may potentially represent a curative option for patients with follicular lymphoma, a condition that, historically, has been considered incurable.

Tisa-cel and other CAR T-cell products targeting CD19 currently approved by the FDA for large B-cell lymphoma but not yet for follicular lymphoma, may also be soon approved by the FDA for patients with follicular lymphoma based on the ELARA study. And we're all eagerly awaiting the results of this study and, potentially, its approval in the next few months.

SONALI SMITH: That's great to hear. And, hopefully, we will continue to have more options, including more cellular-therapy options for patients. So this particular patient proceeded with the standard of care Axi-cel. That went quite well.

There was only grade 1 cytokine release syndrome, no neurotoxicity. And the patient achieved a complete remission on both the day-30 and the day-90 PET/CT. Unfortunately, there was relapsed six months later. So what standard options are there at this time? And would you consider an allogeneic stem-cell transplant at this point?

PAOLO STRATI: So I have to say that, based on some of my data, I'm not surprised this patient did quite well in terms of safety, and I'm very sorry to hear that was one of those few patients who relapsed after an initial complete remission after Axi-cel. In fourth line, our options are a little bit more limited. The FDA has recently approved in fourth line, for patients with relapsed/refractory follicular lymphoma, a new [INAUDIBLE] kinase inhibitor called umbralisib.

[INAUDIBLE] umbralisib response rate is quite similar to other [INAUDIBLE] kinase inhibitors, about 50%. However, the median progression-free survival that, as I mentioned before, is about 10 months for the [INAUDIBLE] kinase inhibitors currently improving third line instead has not be reached yet two years for umbralisib. And also, the toxicity profile seems to be more limited, similarly to idelalisib and duvelisib, more on the autoimmune side. Therefore, definitely umbralisib would be an interesting option for the patient case that you described.

As for your second question, the possibility to use allogeneic stem-cell transplant for patients with relapsed/refractory follicular lymphoma, retrospective studies have shown the allogeneic transplant is effective in follicular-lymphoma patients, particularly those with POD24, like the patient you described in the scenario.

But the transfer-related mortality is significant and needs to be taken into consideration. But most important of all, as CAR T-cell therapy has been approved for follicular lymphoma very recently, we really have no data regarding the use of allogeneic stem-cell transplant in follicular-lymphoma patients who relapse or progress after Axi-cel and CAR T-cell therapy in general.

This last statement really applies to any approach as, again, Axi-cel has been approved for follicular lymphoma only within the last 12 months. And this, once again, emphasizes the importance of translational research and clinical trials for these patients. And as such, I think that, along with umbralisib, there is a standard option. Clinical trial's definitely the best option for patients with follicular lymphoma whose disease is either refractory or relapses after CAR T-cell therapy.

SONALI SMITH: Yes. Thank you for these insights, Dr. Strati. I agree. The post cellular therapy, or the post CAR-T space is a very challenging situation, and I appreciate your perspectives. So as an update, this patient received umbralisib for six months and had an initial response with a partial remission but eventually progressed and then proceeded to a clinical trial, now on a novel oral-immunomodulatory agent and has been in a complete remission for four months.

PAOLO STRATI: That's great to hear. And I hope that this remission will be durable, emphasizing, again, the importance of clinical trials for patients with lymphoma in general, and particularly, those who relapse or are refractory to standard treatments. It was very interesting to listen to this case. Thank you for asking your question, Dr. Smith.

I'm going to ask your opinion now about a second case. This is a 67-year-old man with diabetes that has a long-lasting history of rectal bleeding, for which he underwent a colonoscopy in 2016 that revealed hemorrhoids and scattered polyps that were not malignant on biopsy. However, as part of routine follow-up, a colonoscopy was repeated five years later, and this, unfortunately, showed diffuse nodularity of the colon with several areas of ulceration. Biopsy of the nodules showed a mature B-cell lymphoma, CD20 positive, CD5 positive, BCL2 positive, SOX11 positive, but negative for CD10.

FISH testing confirmed a translocation 11;14. There was no evidence of TP53 mutation, and Ki-67 was 40%. So Dr. Smith, what do you think about the overall potential histological diagnosis? And how do you approach this patient in terms of staging and prognosis discussion?

SONALI SMITH: Yes, so this poor patient, with long-standing rectal bleeding-- I mean, this can happen. It's not a very common presentation for mantle cell lymphoma, but we know that mantle cell lymphoma is very likely to involve the GI tract and can often be extranodal.

In terms of the histology itself, this is very classic. The co-expression of CD20 along with CD5 is only seen in CLL and mantle cell lymphoma. And in this case, the mantle cell lymphoma's confirmed by SOX11 positivity, CD10 negativity, and then, also, of course, the FISH [INAUDIBLE] translocation of 11;14 with a cyclin-D1 overexpression.

When it comes to prognosis in mantle cell lymphoma, there's a number of different prognostic indices, but the two biologic features that I think are most important are P53 status, as well as the proliferation rate. Patients who have a TP53 mutation typically have chemo-resistant disease. And we have no really good approach in terms of how to treat these patients the best.

PAOLO STRATI: Thank you, Dr. Smith, for outlining the diagnostic and prognostic approach to patients with mantle cell lymphoma. You alluded in your answer about the regenerative treatments, so I wanted to ask you, how do you, in general, treat patients with mantle cell lymphoma and, more specifically, this case. And also, we keep dividing patients with mantle cell lymphoma in transplant-eligible and ineligible, but the big question is, do all patients who are transplant-eligible need transplant? And what's year overall approach to this major dilemma?

SONALI SMITH: Yes. That's a really good question. The general approach to treatment for mantle cell lymphoma is based on the concept of fitness and age. So we end up dichotomozing patients into one of two groups. They are either young and fit, or they are older and unfit.

And, of course, this is somewhat controversial because age itself is just a number, and there is significant variability based on function and other medical conditions. Complicating that further is that many clinical trials have used 65 as the arbitrary cutoff between young and old, whereas some transplant studies have actually gone all the way up to age 70. So if I focus on the fact that this is a 67-year-old man who has no real significant history and clearly has a disease that needs treatment, my general approach has been to follow the younger-and-fit approach.

And as you mentioned, the historical approach to this has been to think of treatment in three phases. There is induction, there's consolidation with a high-dose chemotherapy and autologous stem-cell transplant, and then there is maintenance rituximab for three years, which has been shown to have a survival advantage. But your question-- I think there are many unanswered areas when it comes to approaching a patient who is going to be treated with an aggressive multimodality approach.

So first, in terms of the induction itself, there is data that cytarabine-based regimens likely achieve a deeper minimal residual disease state than aklylator-based therapy. And so cytarabine-containing regimens have really become the standard of care against which other regimens are compared. That being said, there was at least a SWOG study that randomized patients between BR and hyper-CVAD and found that BR was a sufficient type of induction.

And some of this controversy led to an ongoing Intergroup trial, which is EA4181, that takes patients with newly diagnosed mantle cell lymphoma, previously untreated, like our patient, and randomizes them to bendamustine, rituximab with or without cytarabine and with or without a BTK inhibitor, in this case, acalabrutinib. So outside of a clinical trial, I would use a h based induction regimen, but I have preferred to put most patients onto that.

But your second question, which is, do all patients need high-dose chemotherapy and autologous stem-cell transplant, is really important. This is associated with a need for inpatient admission, high-dose chemotherapy with subsequent late toxicity. And remembering that mantle cell lymphoma remains an incurable disease, the question is whether or not all patients should get this.

So to address this, there is the EA4151 trial, which is also being done through the United States Intergroup. And this is using a very unique minimal residual-disease assay to randomize patients to either transplant plus maintenance or maintenance alone. And so this is a next-generation sequencing test. And if patients have a negative MRD status at a very deep level, then patients will get randomized to one of those two arms, whereas if they have minimal residual disease that is detectable, then they will go ahead and get the standard of care.

So for this patient, he opted to be on the clinical trial and was randomized to BR, plus cytarabine, plus acalabrutinib. But outside of a trial, I really would have considered intensive induction, including the Nordic regimen that includes high-dose cytarabine, followed by transplant and maintenance rituximab.

Now some may argue with me that this person is 67 years old, and the Nordic regimen is quite intense. And I think this is where some of the art of medicine may come in. And, hopefully, we can have some type of assessment tools to better predict who can tolerate intensive induction. But I'm quite impressed by some of the transplant data that do lead to seven- and 10-year remissions in some cases. Of course, this new trial will tell us whether or not we're overtreating many of the patients, particularly based on their MRD status.

PAOLO STRATI: Thank you, Dr. Smith. It was very helpful. I think you outlined really well how challenging it can be to treat patients with mantle cell lymphoma and how important it is to tailor treatment based on biological but also, patient-related data.

This is all that we have for today. Thank you, Dr. Smith, for a very delightful conversation. It's been very helpful to review together today the treatment of patients with follicular lymphoma, and mantle-cell lymphoma, and safety and efficacy of novel therapies for these patients.

Thanks, everybody. And, particularly, thank you to all the listeners who tune in to this episode of the ASCO Education Podcast. And thank you, Dr. Smith, for your time.

SONALI SMITH: Thank you. It was such a pleasure to have this conversation today.

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It's not an insurmountable challenge, but it's a whole new world for traditional prescribers who are used to writing a prescription and defining what is the active ingredient, how often a patient will take the medicine, by what means. DANIEL BOWLES: I think the other thing we need to be very aware of, as hopefully people are listening to this across the country and elsewhere, is the laws vary wildly from jurisdiction to jurisdiction about what consists of medical cannabis, who is allowed to use it, and in what quantities. So I think it's really important that as we learn about these and we think about these, we think about how they apply to any of our specific situations in which we live in practice. KENT HUTCHISON: So it's interesting-- just follow up on what Dr. Braun and Dr. Bowles, what they're saying, those two words-- right-- medical and cannabis. I think the medical part is somewhat easier because it can refer to the reason the person is using. Are they using for medical reasons are they using for recreational reasons, even though that's a blur? But the cannabis part I think is what's really complicated. And this is what Dan was getting at. All the different products, all the different cannabinoids, I mean all the different bioactive terpenes and everything else in the material, all different forms of administration. That is where it gets super complicated to really define what that is. And then of course, there's so little research we don't really know what all those constituents do. ASHLEY GLODE: Now that we kind of have a little bit of familiarity with medical cannabis, can you comment on adult use cannabis and what that might mean for a patient? ILANA BRAUN: Ashley, I think it's a really good question. And in some of the early research I did to try to understand where medicinal ended and adult use began, or adult use ended and medicinal began, I began to discover a theme that emerged, which is they sort of blend into each other often. In other words, some of the oncologists that I spoke to believed that it was not such a bad thing for a patient with serious illness, and pain, and many other symptoms to have a sense of high or well-being. And conversely, when I spoke to patients using cannabis, sometimes a cancer patient used medicinal cannabis for enjoyment, and sometimes they used it for symptom management, and sometimes they used it for both. And so I think it is somewhat of a slippery slope between the two. Would you agree? DANIEL BOWLES: I think there are definitely blurred lines between the two. I think that the advantages of what most states would recognize as medicinal cannabis is usually they're less expensive, patients can use them in larger quantities. There are certain advantages. But there's also paperwork that goes along with medicinal cannabis that some patients don't feel comfortable with. Or particularly I think when you have a patient who's interested in trying cannabis or a cannabinoid for the first time, they might not want to go through all the extra steps required getting that medical marijuana card, whereas adult use, I think people feel more comfortable, at least in my state, sometimes walking into a dispensary to discuss the options with people who work at the dispensary and then get it from more of an adult use or recreational cannabis initially. And then if that's something that they find helpful for their symptom management, to then take those extra steps and try to get a medicinal card. ILANA BRAUN: I agree with Dr. Bowles that the target symptoms or the target effect is often similar and access can differ. KENT HUTCHISON: Yeah. Just to chime in, I agree. I agree also. It's definitely-- the lines get blurred. The recreational user might also appreciate-- for example, college students, I hear them say a lot of times that they appreciate some of the anxiety-reducing aspects-- right-- even though they're not necessarily a person who has an anxiety disorder. And then of course, patients appreciate a slight increase in euphoria or positive affect, and what does that mean? Is I mean they're also using for recreational reasons? Or is that completely, I guess, legitimate? On the other hand, there are sometimes I feel like when-- especially on the recreational side-- when people are using for the more psychological effects, the sort of psychotropic effects, I know sometimes the medical patients refer to that as being a little bit loopy as a side effect. So I feel like there's definitely some blurred lines. And maybe there are some places where we can think about in perhaps in a less blurred kind of way. ASHLEY GLODE: How often do you guys have a patient ask you about medical cannabis? And what are the most common questions they might have for you? ILANA BRAUN: In my psycho-oncology practice, patients frequently tell me they're using cannabis, often with good effect and minimal side effects for polysymptom management-- for instance to address nausea, or pain, or poor appetite, or sleep, or mood, or quality of life. But they don't ask me a lot of questions. For instance, one of my longest-standing patients. A man with metastatic cancer and gastroparesis. Vaporizes cannabis before meals to keep his weight up. And many of my patients also use cannabis as cancer-directed therapy. And for these patients, side effects can sometimes be more pronounced. For instance, I have a lovely patient with metastatic cancer who follows a Rick Simpson protocol. So what is that? That's an online recipe marketed with an antineoplastic claim. And so this patient targets hundreds milligrams of cannabinoids daily. And with such high cannabinoid doses, she sometimes feels spicy, or out of it, as she describes it. And then I had another patient who targeted high daily doses and developed a debilitating nausea and vomiting that was initially diagnosed as chemotherapy-induced nausea vomiting because it was so hard to tease out in the setting of so many medicinal agents, what was what. But the symptoms resolved completely within weeks of the cannabinoids being halted. And so as I mentioned, what's notable about all three of these patients, and many of the others I see, is that they are quite open with their oncology teams and me about their medicinal cannabis use. But they don't seem to rely me or other members of their oncology team for their therapeutic advice . We insert ourselves when we see potential harm, but much of the decision-making seems to be made-- I don't know in the naturopath's office, at the dispensary counter, or by trial and error. And this anecdotal experience in my practice is borne out in my research findings as well. Patients are just not getting the bulk of their cannabis therapeutics information from their medical teams. DANIEL BOWLES: In my clinical practice, I am asked about cannabis or cannabinoids a fair, amount often in the context that Dr. Braun is describing, where a patient is coming in and they're already using a cannabinoid or they are planning on doing it and they just want my opinion. And I think unlike talking about more conventional cancer-directed therapies where they really rely, I think, on their medical team for information and guidance, we are often more a supplement I think in terms of information. In terms of the patients who come to ask me about cannabis or let me know that they're using cannabis, it's a very wide selection of people. I see young people, old people talking about it, men, women, a variety of different malignancies. So there really is a lot of usage or are thought about usage of cannabis or cannabinoids amongst our cancer patients. I think if you look at the studies, they'll tell us that depending on where we're working, anywhere between 20% to 60% of patients have used cannabis in the last year to help manage some sort of cancer-related symptoms. And I think the other thing that is notable is you'll find people asking about cannabis or cannabinoids who I think we might not have otherwise expected. So for instance, Just this past week, I had a patient with anaplastic thyroid cancer in his 70s, and his daughter was wondering whether he could try CBD to help with his sleep and anxiety. She wanted to make sure that it wasn't going to interact with this cancer therapies. And I appreciated her bringing it up, and we could have a frank discussion about the pluses and minuses of it, just like we might any other therapeutic intervention. So I think that particularly as the laws have changed across the country, more and more people are willing to tell us that they're trying cannabinoids and cannabis than maybe would have even 10 or 15 years ago. KENT HUTCHISON: I think in an ideal world, patients would be talking a lot more with their physicians about this topic. And I think unfortunately that a lot of people do get their information from dispensaries. From the media, from social media, from their kids, and from whoever. And I think that's something that I hope will change in the future. DANIEL BOWLES: In terms of questions that I'm often asked, I'll be asked if it's going to interact with their cancer treatments, in terms of making their medications more or less effective. I do get questions about how I think their cannabis use might affect some of their symptoms. I get questions about other drug-drug interactions-- let's say, interactions with opiates, or benzodiazepines, or some of these other medications that a lot of our patients are on. ASHLEY GLODE: In a recent survey 80% of medical oncologists who discussed medical cannabis with their patients, 50% recommended it in the past year, but only 30% felt knowledgeable enough to make recommendations. What do you guys think needs to be done to address this knowledge gap? And what resources do clinicians have to get and stay informed? DANIEL BOWLES: So I'm a big fan of the NCI's PDQ as a great resource. It has a fairly objective information about cannabis and cancer specifically. So I think that's a nice reference for people who are interested in getting an initial overview on the topic. I think there are also a number of different educational programs. I know the University of Colorado, for instance, has a Cannabis Science Master's and also a certificate program. So there are courses available for people who want to educate themselves more on this topic. ILANA BRAUN: Yeah. I guess when I think about what needs to be done, I think that cannabis needs to become a routine part of medical training curricula and CME programs. I think that a federal funding for high-quality clinical trials and a loosening of federal restrictions on accessing study drug were to occur, that would be really a big boon for the medical community. And my colleagues on this podcast I know are doing some very creative pragmatic clinical trials naturalistic studying what is happening in the field. And I am doing clinical trials using an FDA-approved version of cannabinoids. But it's still very hard to study whole-plant cannabis in a form that is sort of a standardized trial drug in a cancer patient. And then when I think about where I would begin to read, I don't think there is a single source, unfortunately. But a great place to start reading is actually a project that Dr. Hutchinson was a part of, which was an expert panel that was assembled by the National Institute of Science Engineering and Medicine in 2017. And they produced a monograph on the health effects of cannabis and cannabinoids. And it's several hundred pages long, including sections devoted just to oncology. So in other words, there is scientific evidence to evaluate, and it's sizable. DANIEL BOWLES: The Austrian Center for Cannabinoid Clinical and Research Excellence also is a helpful resource. One of the nice things about that is they actually give some dosing suggestions or ideas for people who really don't quite know where to start. Right now, there aren't a lot of people in that position to say, here's how it should be done. Here's how it gets dosed. Here are the data to support those decisions. And so the folks in the next level of training don't learn it in the same way that we have learned how to prescribe other medications. And they can't then lay it down. So because the data are scant, in some respects, and particularly for herbal products that So. Many of our patients are using, I think it falls outside the medical model that we've all become so used to using to learn how to take care of patients. And I think that's one reason that so many oncology providers feel interested in learning more about this topic, but don't feel comfortable giving patients guidance on how to use them. KENT HUTCHISON: So both Dr. Braun and Dr. Bowles identified some of the key resources out there. And certainly the training issues that Dr. Bowles just talked about are important. And I do want to emphasize the one thing that Dr. Braun mentioned, which is basically that we do-- we lack research and we lack data on some key important issues, like dosing, for example. What dose is effective? So cannabidiol has been out there for a long time, but what dose is effective for what? We don't know, right? So we definitely lack research. And there are definitely obstacles to doing that research. ASHLEY GLODE: So you guys brought up some good points about there being a lack of data, but also there is some evidence. So what is the current research and evidence on the efficacy of medical cannabis for management of cancer symptoms and cancer pain, specifically? DANIEL BOWLES: So there was a really nice review article that just came out in the BMJ looking at cannabis and cannabinoids, not specific to cancer pain, but including cancer pain. And what they found-- they looked at different preparations from herbal products-- smoked herbal products, oral agents-- cannabinoids, more specifically. They found there is a modest, but a real improvement in pain in patients or research subjects treated with cannabinoids versus those usually typically treated with placebo. In particular, the data are supported in neuropathic pain, I'd say more so than the other pains. I think the data are less compelling with regards to many of the other symptoms that people often use cannabinoids for, such as sleep, anxiety, appetite, things along those lines. ILANA BRAUN: So I'll tell you a little bit about how I think about the evidence base in oncology for cannabis use. So I'll preface this with two points. The first is that, as I mentioned, cannabis products tend not to be one active ingredient, but hundreds of active ingredients-- cannabinoids, phenols, terpenes, they all have bioactivity. And they don't work individually, they work through complicated synergistic and inhibitory interactions that have been termed entourage effects. So I don't think one can easily extrapolate from clinical trials of, say, purified THC, to understand whole-plant cannabis' activity in the body and how it might perform in humans. And then the other point I'll make is that when I think about the types of clinical evidence that we as clinicians hold dearest, it's clinical trials of our agent of interest in our population of interest. So cancer patients using whole-plant full-spectrum cannabis that they would access at a dispensary or grow in their own home. With this in mind, I believe the strongest evidence, randomized double-blind placebo controlled trials of whole-plant cannabis and oncology populations begins to support its utility for chemotherapy-induced nausea and vomiting. So there have been a few studies that have looked at this. But just in 2020, the most recent is a study by Grimison, et al. It was a multicenter randomized double-blind placebo controlled crossover trial comparing cannabis extract. And I think the extract they use was a 1 to 1 THC to CBD ratio versus a placebo in patients with refractory chemotherapy-induced nausea and vomiting. And what they found was that with active drug, there was a complete response in 25% of participants versus only 14% with the placebo. And although a third of participants experienced additional side effects with the active drug-- so remember, this was a crossover trial, so they saw both arms-- 80% preferred cannabis to the placebo medication. So that's clinical trials of cannabis and cancer. But if we expand the base of the pyramid of acceptable evidence to include high-quality clinical trials for health conditions other than cancer and extrapolate back, then I agree fully with Dr. Bowles that there's a growing body of evidence that cannabis may be beneficial in pain management. And there have been many clinical trials done in this arena, and they span myriad pain syndromes, including diabetic neuropathy, post-surgical pain, MS pain, sickle cell pain. And so it does seem like cannabis works for pain management in several other illness models, so we could extrapolate back and hope that it works in cancer pain. And then there is a small body of evidence with nabiximols, which is a pharmaceutical that has a 1 to 1 THC to CBD ratio. And it's a sublingual metered dose spray. And it has been trialed for opioid-resistant cancer pain. And this is not as a single agent, but as an adjuvant to opioids. In early trials, two times as many participants in the active arm as compared to the placebo arm demonstrated a 30% pain reduction. And for the pain specialists who are listening, they will know that is a substantial pain reduction. But then, additional studies fail to meet primary endpoints. I think there were three clinical trials that followed. Nabiximols was found to be safe and effective by some secondary measures, but the FDA opted not to approve nabiximols for cancer pain. So I think there's some suggestion of effect, but there's some smoke, but no fire-- no pun intended. DANIEL BOWLES: I think many of the studies that have been done looking at cannabis-- or cannabinoids-- have been compared to placebo or they've been crossover. And I would say fairly consistently, there is some improvement in pain scores with the cannabis products versus placebo kind of across a wide variety of disease spectrums with regards to pain. I think one of the other questions that a lot of people have asked is, can you decrease people's opiate usage using cannabis? As we know, there's a huge epidemic of opiate misuse in the United States of America right now. And I think many people are looking for ways to decrease opiate usage. There was a nice study done from Minnesota in conjunction with the Minnesota dispensaries-- or state marijuana program-- where some researchers randomized people to starting kind of herbal cannabis products early in their study or three months into their study. So it was kind of a built-in control. And they looked at opiate usage rates, pain scores, quality of life scores, et cetera. What they found is there, again, was some improvement in pain control overall in the cannabis users. However, it did not equate to a decrease in opiate usage. So I think that it's an open question that I think a lot of people want to know the answers to before they start recommending or incorporating cannabis or cannabinoids more widely into their practice. KENT HUTCHISON: It's certainly a complicated issue, in some ways, right? Because the research which is summarized very nicely by both Dr. Braun and Dr. Bowles, it is suggested, but not overwhelming, by any stretch, right? It's not clear-cut. And I think that one of the big issues here we talked about the very beginning is how complicated this cannabis thing is. and Dr. Braun alluded to this also, that there are obviously many different formulations, many potentially active constituents in cannabis. And so what has mostly been studied so far is either synthetic versions of THC or nabiximols, which is probably the closest thing to what some people are using. So I think the jury's still out, for sure. And I think hopefully at some point, what will happen is that some of the products that are actually being used by people-- because most people aren't using nabiximols, most people are not using THC only, hopefully there'll be some trials of the things that people are actually using out there in the real world that will tell us something more about whether it's effective or not. And maybe even more specifically, which constituents-- which parts, together are most effective with respect to pain. DANIEL BOWLES: I think one of the other topics that some of my colleagues have alluded to already is not just cannabis' role in symptom management. I think pain is often what people think of, and people are using it for chemo-induced nausea and vomiting, anxiety, sleep, appetite, but a fair number of patients are also using cannabis or cannabinoids with the hopes that it is going to treat their cancer like a chemotherapy or an immunotherapy may. And oftentimes, patients will point to preclinical studies looking at oftentimes very high doses of THC or CBD that might show tumor cell death or tumor reduction in test tubes. And I spent a fair amount of time-- and I know some of my colleagues spent a fair amount of time-- talking with patients about how it's a big step between cannabis or cannabinoids working to slow cancer growth in a test tube, to working in an animal system, to working in people. ASHLEY GLODE: So what are the most important considerations clinicians should keep in mind before recommending medical cannabis to patients with cancer? DANIEL BOWLES: We should be asking why they want to use cannabinoids. I think just like we might any other medication that people are thinking about trying-- or herbal product that people are thinking about trying-- I think we need to ask why they're interested in using these products. So is it for symptom management? Is it for some of the ancillary side effects of cannabinoids or cannabis? Why are they wanting to use it? And I think trying to incorporate that more than into the medical model, I ask my patients, hey, if you're using this particular product, do you feel like it's doing what you intended it for it to do? If it is and it's legal in your state, great. Do it as you feel fit. If it's not meeting your goals, if it's not helping with the pain, or if it's not helping with the anxiety, or it's not helping with the nausea and vomiting, maybe we should rethink whether we would use it. Just as if I was prescribing more conventional anti-nausea medication and you didn't think it was working, we wouldn't keep using it. So I think that's a really important thing to keep in mind. I think the other thing to know from a safety standpoint is, who else is in the household? We have a psychiatrist on the call with us today. I think there is an ample amount of data that cannabis is not safe for young people. It's not safe for growing brains. And I think we need to make sure, just as we would want people's opiates to be secured, that their cannabinoids and cannabis products are secured as well, from those who do not want to use them. ILANA BRAUN: And the thing I would keep in mind is that in most states, giving patients a medicinal cannabis card is allowing them to access any number of products with different ratios of active ingredients, delivery mechanisms, onset of action, potencies. And if you don't discuss all of these issues with your patients, these are things that they will decide at the dispensary counter, or by discussing with friends and family, or by trial and error. And I think it's really important that we clinicians guide this narrative. ASHLEY GLODE: So what kinds of patients are not good candidates for medical cannabis? DANIEL BOWLES: I would not recommend medical cannabis for people who can't meet some of the criteria we already discussed. So people who can't keep it safe in their households or have concerns about diversion in their own households. Those are people who I think would not be great candidates for medicinal cannabis or cannabinoids. ILANA BRAUN: As the psychiatrist on the call, I would add that I worry for people with a strong history of psychosis, or currently psychotic, or with a strong family history of psychosis. And perhaps those severely immunocompromised, since there is evidence of fungal and mold contamination in some cannabis products. DANIEL BOWLES: The other group of people I discussed this with are patients on immunotherapies. One of the ways that cannabis may be effective in some of the symptoms we discussed is it's an anti-inflammatory agent. One of the ways it could be detrimental for patients on immunotherapies is that it's an anti-inflammatory agent. There is one small study that suggested that patients might have worse responses to immunotherapy who are cannabis users versus those who are not. So that is a conversation I like to have, just so patients feel like they can be informed. I think lastly, cannabis even for people with medical cards, is not free. So there can be a financial burden for people who are using it. So that's something that I'll often bring up with people as well. KENT HUTCHISON: One thing I would add to this would be history of a substance use disorder might also be a consideration here as well. Mainly because you don't know what the person is going to get, and it could be something that lends itself to relapse or encourages a problem. So I would add that to list. ILANA BRAUN: And I would second what Dr. Bowles said about the financial challenges of using cannabis regularly medicinally. It's not something that's covered by insurance, either. So these are out-of-pocket expenses, and they can add up fast, particularly for patients in the oncology space using it for antineoplastic therapy. ASHLEY GLODE: So is there a concern about drug-drug interactions for patients currently undergoing active cancer treatment? DANIEL BOWLES: There are some data that there can be drug-drug interactions with cannabis and certain agents. In particular, cannabidiol, or CBD, is a CYP3A4 inhibitor. And there are a lot of drugs that are metabolized through that particular system. So I think that that's the clinical relevance of those interactions, I think, is sometimes unknown. But that is another topic that I do think we need to make sure we bring up with our patients. ASHLEY GLODE: Thank you. Yeah. So a lot of what we'll do is from a drug interaction perspective, use the FDA-approved products that we have available to run through a drug interaction checker, like Dr. Bowles mentioned. So we'll use dronabinol as the THC-based product and epidiolex as the CBD-based product. There's also some resources, such as natural Medicines Database. And some of the pharmacy programs that we use, you can actually put in marijuana or cannabis as a drug and run drug interaction checks. So there's multiple potential interactions, like he mentioned, through the immune system. But through the cytochrome P450 pathway, cannabis has been shown in some instances to be an inhibitor, sometimes an inducer of certain enzymes, as well as a substrate. So it's really important to work with your pharmacy colleagues to run through different potential interactions that may be present. ILANA BRAUN: I'll just add one thing, just in case that's helpful. I mentioned earlier in the episode that I had a patient who used cannabis as an antineoplastic drug, and targeted very high doses and developed a terrible nausea and vomiting. And when she stopped, so did the nausea and vomiting, even though her chemotherapeutic continued. And I, to this day, don't know if that was a cyclic nausea and vomiting syndrome, which has been known to plague some heavy cannabis users, or whether drug-drug interactions led to her high-dose cannabis triggering high blood concentrations of her cancer-directed therapy at the time. And so I think that drug-drug interactions do need to be carefully weighed. ASHLEY GLODE: So wrapping up, has the medical community stance on medical marijuana shifted in recent years with legalization in many states? ILANA BRAUN: I don't think we know the answer to this, about how sentiment has shifted because there aren't longitudinal studies that I know of examining this question. But we need some. And one could imagine that as medicinal cannabis becomes are commonplace, providers are increasingly confronted with questions about how to guide care and the desire for high-quality clinical trials and in-depth cannabis therapeutics trainings increases-- and as one piece of evidence for this, at the end of 2020 the National Cancer Institute held a first-in-kind four-day conference at the intersection of cannabis and cancer. And so I'm hopeful that grant opportunities will follow from that. DANIEL BOWLES: I think overall there has been more willingness to discuss cannabis in the context of patient care in the last decade. A couple of ways that I see this is I much more frequently see cannabis use described not necessarily in the drug history, or in the social history, but in the medical history, or in their medications, if they're using it for medical or therapeutic purposes. I think the other place that I've noticed cannabis usage become a bit more mainstream is in the clinical trial setting-- not in clinical trials of cannabis, but one of the things that many of us do is clinical trials of new drugs. And very frequently, 10 years ago we ran into trouble trying to get our patients who were using cannabis products for cancer symptom control onto these clinical trials because of potential drug-drug interactions, or just the fear of the unknown. And I feel like we run into that less commonly now. KENT HUTCHISON: I think it's also worth pointing out that there have been more and more podcasts like this one, right? So to the credit of this organization, I think we are seeing some change. I just wanted to highlight that. And I compliment everyone here for putting us together and putting it out there. ASHLEY GLODE: All right. Well, thank you. That is all we have for today. And thank you very much Drs. Braun, Bowles, and Hutchison for a delightful conversation. Thank you so much to all the listeners tuning into this episode of the ASCO Education Podcast. [MUSIC PLAYING]   SPEAKER: Thank you for listening to this week's episode to make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit elearning.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
  • ASCO Education Podcast podcast

    Oncology, Etc. - In Conversation with Dr. Quyen Chu

    27:17

    This episode features Dr. Quyen Chu, Chief of the Division of Surgical Oncology at Louisiana State University. A prominent surgeon, humanitarian and writer, Dr. Chu shares his life stories, from fleeing Vietnam as a young child, to finding his calling, and giving back through work in impoverished U.S. communities and war-torn regions, including Iraq, Kurdistan and Vietnam. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 01/04/22   TRANSCRIPT [MUSIC PLAYING]   SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] PAT LOEHRER: Hi. I'm Pat Loehrer and director of the Center for Global Oncology and Health Equity, Indiana University. And welcome to another episode of Oncology Etc. DAVE JOHNSON: And hello. I'm Dave Johnson at University of Texas Southwestern in Dallas. Pat, great to have another session today. PAT LOEHRER: It's good to see you again, Dave. I'm really excited about our guest today. And I think both of you and I were talking about this book that came to mind when we thought about having Quyen here. But it's a book by Abraham Verghese entitled My Own Country. And we hope to have Abraham on in another session of ours. You know, Abraham's story of growing up in Africa, and moving to the United States, and moving to the South in Tennessee in a time of HIV was really an extraordinary journey for him. DAVE JOHNSON: Yeah, an amazing story, settling in East Tennessee in the Appalachian Mountains, and then going to the Northeast to do additional training, and then returning to that part of the country during the height of the AIDS epidemic-- really a remarkable story. For those who have not read it, we both recommend it very highly. Today's guests we're incredibly excited about both. Dave and I met Quyen Chu in the Leadership Development program for ASCO. He was in the first class. He's currently the professor of Surgery and chief of the Division of Surgical Oncology and holds the Edward and Frieda Green Professorship in Surgical Oncology at LSU in Shreveport. He earned his MB degree at Brown Medical School in Providence, trained in general surgery in Massachusetts at Springfield and at St. Elizabeth's Medical Center, and then did his fellowship training at Brown University under the mentorship of Dr. Hal Wanebo, who was a wonderful surgeon and very active in ECOG in the Southeast group. Dave and I knew him. He's authored-- or co-authored more than 178 publications, a number of book chapters, a couple of books, including translating one of the surgical textbooks into Vietnamese. He has been an extraordinary human being. And one of the things we want to explore is his journey from childhood until now. In 2013, he was appointed by President Barack Obama to the board of Vietnam Education Foundation. He has worked in impoverished areas in Louisiana but also in the war-ravaged parts of the world, including Iraq, Kurdistan, Vietnam. He is truly a special breed of humanists who-- I think he looks back at his roots. he sees the bright possibilities of the future and reflects on what he can do to make a difference. It's just a great pleasure to have you, Quyen, to join us today. QUYEN CHU: Thank you very much, Pat, for that great introduction. It is very heartwarming, and I look forward to this podcast. DAVE JOHNSON: So Quyen, why don't we start a little bit-- I mean, Pat's mentioned your background. Tell us a little about how you got here and about your family and their journey from Vietnam to the United States. QUYEN CHU: Sure. I immigrated to the United States in 1975 right after the fall of Saigon at the end of the Vietnam War. My father was a South Vietnamese officer in the army, which means that he fought alongside with the Americans so that when the Americans pulled out, South Vietnam fell. And so because he was an officer, we were-- basically had no choice but to leave the country. Otherwise, he would be in a re-education camp, which might mean that we would never see him again. So we left Vietnam in '75. I was seven. We left on a ship, and then we also left-- then we transitioned to boats, and then we went to the Philippines for several months. And then we finally got sponsored by a church in Florida. So then we stayed at Eglin Air Force Base for several months before we actually went to our home in Florida. I grew up there and basically was-- grew up in a very impoverished area. It was-- basically it's a rat-infested home that we lived in. My father was an officer. He was a captain. But coming over to the United States, you have to learn English. You have to try to get a better education. And he finally realized that he had to support a family of six, and he took on being a barber. So he was a barber for most of his-- the rest of his career, really, raising a family of six. And I was there just to do the very best that we could. Throughout it at all, we knew that we were in the right place. And we knew that America doesn't give everything out for free, but we also know that it's a great, great land of opportunity. The philosophy is that if you apply yourself, do the very best, follow the rules and regulations or laws, you know, abide by their laws, that you can do great things. And that is a great opportunity. So that was embedded in me and my sisters, and those philosophies have stood the test of time thus far. PAT LOEHRER: You know, I read a little piece when-- you told a story about arriving here in Florida and a police car pulling up to your house. Can you relate that story? QUYEN CHU: It's the memory that I will never forget. And in fact, I remember it every Thanksgiving. So it was around Thanksgiving. We really didn't know what it was. We just moved into a new house. And it's funny because when we drove by the new house, we saw the garage. And we felt, oh, my god, we're going to live in that garage. This is great. This garage is going to be our house. This is great. There's so much space. And I remember when we asked the driver, the driver goes no, no, no, no, that's where you park your car. The whole house is yours. And we were just amazed. But anyway, so around Thanksgiving, we saw-- a police car drove up to our parkway. And I saw, and I was scared. And then I called out my dad. And I said, Dad, there's a police car here. What did we do wrong? And he was so scared. And he said, Son, you know, I will take care of this. So the police came and knocked on the door. And when my dad opened the door, he claps his hand, and he just bow, just like this, several times to the policemen and say, we're-- in broken English, we're sorry. We know English. We did not mean to break any laws. Forgive us. And the police just smiled. And he says, no, no, no, no. We're here to greet you as a new neighbor. And it's Thanksgiving, and we want to give you a turkey. Then he waved to the other police to come over, and then the other police came out with a big old turkey. And they hand it to us, and they said, welcome to the neighborhood. And we were so happy. My mom-- just about to cry. And we felt that, hey, this is now our new home, and we felt that this is not going to be a strange land, that we're going to create a life for ourselves here. DAVE JOHNSON: It's a remarkable story, Quyen. That type of story just makes it even more special. You mentioned that you had several siblings. Where do you fall in the hierarchy? And what are your siblings doing? QUYEN CHU: So I'm a second-oldest. So my oldest sister-- she went to Cornell, and she is now a full professor of biochemistry at Union College. My younger sister, who's a year younger than me-- she graduated from Dartmouth, and she is now working at industry and also, in the medical field. She holds a PhD from Columbia. And then my youngest sister graduated from Oberlin College, and she is now working in the hotel business. So we're very blessed. We feel very excited about the opportunities. And we look back at our lives every Christmas when we get together as a family, and we reflect back at the lives that we've gotten. And we also feel bad about family members who couldn't make it over here and wonder what their lives would have been like had they come over here. And then we also wonder what life for us would have been like had we not come over here. And through it all, we felt that we really, really hit the jackpot in life and that all of us were very, very lucky to have this life that we have. PAT LOEHRER: I can't imagine the pride that your parents have of all of you and how much pride you have for him. I mean, it's extraordinary. Can you just because I've never-- none of us have been through this, what you've been through. But what was it like being seven years old in the middle of this war in Vietnam? What memories do you have of that? QUYEN CHU: Yeah. I remember when I was playing with my cousins. And of course, in Vietnam, we live under a house full of cousins, aunts, and the extended family. I remember leaving them, and I felt very lonely in America. Of course, each family has its own separate family. And I just felt like it was not-- it was very lonely. But we did have very nice neighbors. We did have great people that really was very supportive. Of course, as a young seven-year-old, the neighbor's daughter was around my age. She was cute, so, of course, I'd find every reason to visit them and say hi to them. But other than that, it was a very nice place to grow up. They have their challenges, obviously. What I remember as a second grader-- I saw all the boys. To me, I thought they were all brothers because they were all Caucasian. They all have blond hair. I couldn't tell the difference who's who, but I thought they were all related. But they were very nice, of course. There were curiosity between us. I've never seen African-Americans until I came over here. And I befriended a Hispanic guy, as well as an African-American, as well as my best friend. To this day his name I still remember. It's Jeff. He was very friendly. Of course, I experienced some racism, but I think that's expected because I look very different. There were a lot of mixed messages coming out of the Vietnam War. But I think that through it all, the challenges, I realized, that there are more good people than there are bad people and that people who were bad-- probably because they were insecure, or they just didn't know me. And then there were those who did finally get to know me. They turned out to be great people. I've learned throughout my 53 years on this earth that people have so many things in common that when we do have conflict, it's probably stemmed from insecurities rather than pure hatred. DAVE JOHNSON: Yeah. You went to undergraduate at Dartmouth. Is that right? QUYEN CHU: Yes. sir. DAVE JOHNSON: So I seem to recall-- maybe you told us this in the LDP program, but you had an interesting experience when you showed up on campus at Dartmouth. QUYEN CHU: Yeah. DAVE JOHNSON: Can you relate a little bit of that to us, as well? QUYEN CHU: Sure. So, again, coming from a family where your dad is a barber, I had limited means. So I basically had, I think, one tote bag that I packed together. I took a Greyhound two day's trip to Dartmouth. And I got there on the campus. It was a beautiful green campus. And I was a little bit hesitant, a little bit reserved because there were a lot of Caucasians and whatnot. And I was a little bit, you know, introvert somewhat. And when I got there, I saw a Frisbee flew by me. And I grab it, and then the guy goes, hey, you want to come and play with us? And I'm like, well, sure. And next thing you know, we hit it off like a bunch of 18-year-old kids-- no worries in our mind, just glad to be on campus. And we hit it off. And I realized that, hey, you know, my reservations were basically based on my own biases rather than the reality. And then I've realized that the reality is that a lot of the kids there are just like me-- just want to find friends, just want to hang out, just want to have a good education. And they weren't being judgmental about anything, and that made me really-- it felt really good. DAVE JOHNSON: Frisbee diplomacy, I guess, is we should call it. Maybe we should throw a Frisbee to Putin. I don't know. QUYEN CHU: That's right. PAT LOEHRER: Tell us a little bit about your journey to become a surgeon. QUYEN CHU: OK. So my dad and mom instilled with me the importance of education. They told me, now listen, you have a choice-- either be in the same rut as us now, or get a good education and get out of this rut. So I really didn't have any choice but to study hard. And I studied hard, and I got an opportunity to go to Dartmouth. I felt very, very lucky with that. They gave me a full scholarship. They believed in me. They saw something in me that I was very happy that they saw. And then I applied to medical school at my sophomore year at Dartmouth, and I got in. I was very excited about that. And I started off wanting to be a pediatrician, but then I realized that what I had to turn in my sheet of the patients that I saw, everything had to do with procedures and techniques. I wrote down there I did a spinal tap, I did a chest tube, I helped intubate, I did all of that. And it was really my pediatric mentor who says, it sounds like you should be a surgeon, not a pediatrician. And that kind of got me thinking about it. And then I rotated a service with Dr. Wanebo and really fell in love with surgery. It was tough. It was rough. But I felt that this is my calling. I felt very fortunate looking back at only the number-- maybe they admitted 100 students. And I felt very fortunate that I was among those. And I knew that it was an opportunity that I did not want to waste, that I did not want to take for granted. I wanted to do everything I can to make sure that I learn as much as I can and hoping that in the future, I would give back to the country, the community that gave me a life. DAVE JOHNSON: Yeah, my mentors suggested that I should be a forest ranger as opposed to a physician. [LAUGHS] PAT LOEHRER: Yeah I think I shared before I got, on one of my medical-school applications, they not only rejected me, but they said, good luck in whatever career you decide to go into. [LAUGHTER] I was going to be a pediatrician, too, but I envisioned all these kids just laughing and having a great time. But they were all crying, and the parents didn't like me either. And so I decided to find a different life. You have had this extraordinary journey of giving back, as I mentioned at the onset, and not only going back to Vietnam but also, going to Iraq and going to many other countries here. And about five years ago, you received the ASCO Humanitarian Award, which was so deserving for you. DAVE JOHNSON: Very deserving. PAT LOEHRER: But tell us a little bit about these efforts. What has pulled you or driven you to do so much of your humanitarian efforts around the world? QUYEN CHU: Well, first of all, I want to credit my wife Trina, who's been there for me. She's basically the backbone of my life, allowing me the opportunity to pursue my passion. She's a lawyer. She put her career in the back seat so that I can have a successful career. So I want to make sure that I acknowledge her sacrifice and her love. Because of her love and her understanding, I was able to pursue my passion, which is giving back. My colleague, Dr. Gazi Zibari is from Kurdistan. And one day, he showed me pictures of the Kurds, and he gave me the history of the struggle the Kurds. And it was reminiscent of the struggles of the Vietnamese, so it resonates with me. And I said to him one day, hey, listen, when you do go, I would love to join you. And so I did. And from that point on, I returned, I think, four or five additional times. We did not return last year or so because of COVID, but we're planning to return again to Kurdistan and Iraq. But it was an opportunity for me to really give back what I wanted to do all along, which is to render care to the less-fortunate individuals of our lives. I also went to Vietnam, Nicaragua, Honduras, and also on those different mission trips. And, you know, Dr. Zibari and I have gone together for many of these trips. And we come to realize, you know, what-- the great thing to do is capacity building. In other words, we should visit these countries not just once but several times to make sure that the surgeons there feel comfortable with the procedures that we taught them and that, hopefully, that they will also teach the other surgeons the procedures, the techniques that we taught them. And we were very pleased when we went back to see that these surgeons were very adept in what they were doing-- Whipples, liver resection. They were doing phenomenal things. In fact, I think the greatest sense of pride in me was to see a young surgeon in Kurdistan who did a laparoscopic right-liver resection bloodless. We felt very proud because-- I was looking at Dr. Zibari, and I said, you know what-- I can't even do that. And it's amazing to see how they have not only learned our skills, but they exceeded us. And isn't that what we all want, that our mentees to be better than us? And so to me, that was a great sense of pride. At the end, the young man came up to me and says, mentor, I hope I did it right. Did I make any mistake? And I chuckled. And I said, no. I could not have done what you've done. You have done amazingly. And he was so happy. He was so proud. He says, I'm so glad that I make you proud of me, Dr. Chu. So to me, that's probably the greatest thing is to see your mentee better than you and still see that respect that you got from them. DAVE JOHNSON: We're really happy you mentioned that because one of the themes of our podcast has been mentor and mentor relationships. And you had a remarkable relationship with Dr. Wanebo. Would you like to expand on that somewhat or tell us about that relationship? QUYEN CHU: Sure. Dr. Wanebo-- I always joke around. I said, Dr. Wanebo, you're a gifted surgeon with an internal-medicine demeanor. He is just so nice. He never loses his cool. And the great thing about him is that every time I have an idea, he would always push me to pursue it. There's never been a, no, it can't be done. No, that's not how-- you will never get it done-- never like that. It's always, this is a great idea, Quyen. Why don't you pursue it. And in fact, he would give me deadlines and say, why don't you get back to me in two weeks and see where we go with that. I remember visiting him in his very busy clinic. And his PA would always trying to brush me aside because they were so busy. And he would always say, no, no, no, come on, Quyen. What do you have for me? What do you need? He would always make time, even in this busy clinic, to help mentor me. And then whenever I'd write a paper or abstracts, he would look at it. He would fix it, and he would send it back to me and ask me to work on it. So he's been a great mentor, just a great person all around. PAT LOEHRER: Quyen, if you could think about a young professional or young student right now and give them some advice, what would it be? QUYEN CHU: I think the best advice is that you pursue your passion. I know it sounds so trite, but pursue your passion. Seek out mentors who believe in you, and avoid those naysayers because I think that young people have so many insecurities. And they're great people. They're so naive, and they're so fresh. They're not tainted with all of the flaws of the world. And I always worry that when they encounter negative people, it fills their mind with negativity. And that, to me, is not very constructive. So I would advise young people to seek out optimistic, idealistic people to be mentors. And then I think the rest will follow. And they will learn what can be done, what can't be done. Obviously, you need a mentor to advise them so that they don't fall into your trappings of making major mistakes. But I think that mentors should be someone who is inspiring, who is positive, who can tell them that, hey, you can do it. And if you fail somewhat, it's not the end of the world. Seek out your passion, and never give up. DAVE JOHNSON: That's great advice, Quyen. I have just one more question I wanted to ask and perhaps should have asked a bit earlier. How did you end up in Louisiana? QUYEN CHU: That's a great question. So at the end of my fellowship, I had opportunities to stay up north. Then I got a call from my previous partner to say, hey, listen, I'm in Shreveport. Why don't you come by. In fact, it's funny because when I heard the word "Shreveport," it sounds, to me, Chinese. And I said, why would I want to go to China to practice? I didn't know where it was. And then they said, no, no, this is in Louisiana. And I really thought about, nah, I don't want to go. But my wife said, listen, why don't you just go down there and take a look so that at least you won't offend the person who asked you to come down. So I went down there for an interview. And it really resonates with me about the needs, that patients there did not have, in my opinion, good surgical oncology care. There was a huge need. I saw the mortality for esophagus, gastric cancer. They were high. I saw a lot of cancers that were neglected. And the chair there, Dr. Turnage, was wonderful. And he said, listen, Quyen. Nobody's going to compete against you. We just got a huge need. I think that you would find a niche here, that you can really, really develop a practice here, and then I can mentor you for the academic part. So I thought about it. And then I talked to Trina, my wife. And I said, this is what I wanted to do. I wanted to give back. I didn't want to be just another spoke on the wheel. I wanted to make a difference. I think I can do this here. And so we took a chance, and I think that we're very happy with that decision we made. PAT LOEHRER: Well, Quyen, I just, as I reflect on this and think about that leadership-development program, there are many different kinds of leaders, but I can't think of a person who serves as a better example as a servant leader than you. You have given of yourself in so many ways. In this particular past few years. Where there's been so much angst and polarization in this country, and even consideration of isolationism and not having immigrants come into the country, I hope people listen to this, the podcast, and realize what the impact was of a man and a woman who decided to bring their kids over here. And he became a barber, which is not that prestigious of a job, if you will. But his impact on this country is huge. Mark Twain had a little quote. He said, "The two most important days of your life are the day that you were born and the day you find out why." And when you guys were born in Vietnam, you had no clue what was going on, but you are one of the fortunate people who know why you're here, and that's to make a difference. And I just want to tell you that you have. Thank you so much for your time with us today. DAVE JOHNSON: Yeah, it's been great. QUYEN CHU: Thank you very much. DAVE JOHNSON: Quyen, this has been marvelous, and we're both great admirers of yours. And I could not agree more with Pat about the impact that you've had. One thing we like to do with our guest at the end is ask you if there's something you've read recently, or a documentary, or something, a movie or something you've seen that you would recommend to us and to our listeners. Is there something special that you've read recently or maybe seen that you'd like to recommend? QUYEN CHU: Yes. So there's a book by Mr. David Epstein called Range. It's a phenomenal book. It's a book that contrasts Malcolm Gladwell's philosophy about 10,000 hours to be an expert. Mr Epstein took a different approach. He took the approach that you have to be a generalist. In other words, you have to do many things in life before you can hone in on one particular skill set to become an expert in that. So to me, that book, Range, is a fascinating book. I'm midway through. And it's just-- it's a beautifully written book, and it just gives a different perspective of life. I've always loved books that give a different perspective for a particular topic. And I would highly recommend our readership to read Range by David Epstein. DAVE JOHNSON: Yeah. I also read that, and it is a fabulous book. I couldn't agree more. QUYEN CHU: Yeah. DAVE JOHNSON: Well, we've come to the end of our session. And I really want to take this opportunity to thank our listeners and thank Quyen for joining us. It's been a marvelous session. QUYEN CHU: I appreciate it. Thank you, David, and thank you, Pat. DAVE JOHNSON: Thanks for tuning in. This is an ASCO educational podcast, where we will talk about anything and everything, really. We really will. So if our listeners have any ideas for our topic or guests that you'd like to hear, please email us at [email protected] Thanks, again, and remember that November 9 is National Louisianan Day. And Pat, just so you know, November 16 is National Indiana Day. I'm sure you already knew that. PAT LOEHRER: I love it. Every day's Indiana Day. DAVE JOHNSON: No, every day is Texas Day. PAT LOEHRER: Thanks, guys. [MUSIC PLAYING] SPEAKER: Thank you for listening to this week's episode. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.
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    Cancer Topics – Beyond Adjuvant Chemotherapy: Precision Oncology in Early-stage NSCLC

    31:03

    Adjuvant immunotherapy is a game-changer for early lung cancer, but it is not the best choice for every patient. Hosted by Dr. Rami Manochakian (Mayo Clinic), Drs. Karen Kelly (University of California Davis) and Howard West (City of Hope Cancer Center) explore considerations in shared decision making and personalizing therapy through patient cases.  Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 12/15/21
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    Oncology, Etc. - From Personal to Politics – A Discussion about COVID and Oncology

    29:15

    In this episode, oncologist Bryan Schneider and infectious disease expert Adrian Gardner from Indiana University, share what it has been like to get knocked down with COVID-19 twice, care for patients during the pandemic, lead the University’s COVID response, and even a supreme court case on vaccination. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 12/7/21   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. PAT LOEHRER: Hi. I'm Pat Loehrer. I'm a director of the Centers for Global Health and Health Equity at Indiana University Simon Cancer Center. DAVE JOHNSON: And I'm Dave Johnson. I'm a medical oncologist at UT Southwestern in Dallas, Texas. PAT LOEHRER: Well, welcome back to ASCO's education new podcast series entitled Oncology, Etc. Today, we'll be joined by two outstanding guests, Dr. Bryan Schneider and Dr. Adrian Gardner. We're going to do a deep dive about COVID-19. And Dave, I was thinking-- I was reflecting on my life. The thing in medicine is when new diseases come out. So in our earlier lives, when we started there, was no such thing as Lyme disease, HIV/AIDS-- tumors didn't exist. And then just in the last couple of years now, we have COVID-19, the SARS CoV 2. And I think as physicians, it's kind of exciting. What's your experience been with the COVID-19 in the wards at Parkland? DAVE JOHNSON: Well, it's been really, very challenging. You know, I don't know that the public yet has fully grasped the magnitude of this disease. I mean, 700,000-plus Americans have died of this disease. That's an astonishing number when you think about it. And I was just on the general medical wards just a couple of weeks ago with a wonderful team of residents and students. Patients with this disease are very sick. We often downplay it, but I'm telling you, these people are really quite ill and can get ill and symptomatic rapidly, within hours. So this is a serious illness. But I agree with you. One of the things I told the residents a year ago was to keep a journal, that there are a few times during the course of your training and career where a new disease emerges, and you can be part and parcel of that. And keeping a diary of what happened is something that I wish I had done when AIDS emerged back in the '80s, or other disease processes, like Lyme, as you mentioned. PAT LOEHRER: And syphilis for you, wasn't it? DAVE JOHNSON: Well, that was sort of the [LAUGHS] Hippocratic oath days, but yeah, no. I think that was-- I think-- I can't remember. We were hanging out together at the time, so I don't remember exactly. Yeah, no, it's been really remarkable. The thing that's been interesting to me is the response of individuals and their families to the disease, particularly once the vaccines came available. So maybe we can delve into that a little bit today, because I know one of our guests has actually experienced that himself, so we'll know more about that later. PAT LOEHRER: I don't think, to be honest, that we could have a better collective wisdom than we have today with Dr. Schneider and Dr. Gardner, who will talk about their personal and professional and I think the global impact of COVID. I don't think there's any two people better than that. The only thing we could do better is if Anthony Fauci was here by himself. But these guys are tremendous people. Dr. Gardner went to medical school at Brown, did his fellowship and infectious disease at Beth Israel, and then did his MPH at Harvard, and joined the faculty in Indiana University in 2012. When he was a student, he spent time in Kenya, with Joe Mamlin from Indiana University as part of the AMPATH program. And he came back to become the field director there. And he is just an outstanding person. He's now the director of the Center of Global Health for Indiana University and the Associate Dean for Global Health and has led the contact tracing for Indiana University. And he's going to give us some input from this. Bryan, again, I've known forever. He's just an outstanding medical oncologist. He is now a Professor of Medicine and Medical and Molecular Genetics here at IU. He's a Vera Bradley chair of oncology. He is the founding chair of our precision genomics program and just a superstar in breast cancer as well as pharmacogenomics and was one of the first to describe the unique neuropathy associated with the taxanes in breast cancer. So it's just a pleasure to have both of you here. DAVE JOHNSON: You know, Pat, it's great to have that talent there. It balances out the negativity of other faculty members. But that's great. Welcome, both of you. PAT LOEHRER: I loved you a minute ago. I've turned mute on from a distance here. Adrian, tell me a little bit about yourself, growing up and how you got to where you were. ADRIAN GARDNER: Sure, thanks. And thanks so much for the invitation and for being part of this and for the generous introduction. So as you said, Pat, I'm a product of an international environment. That's an important part of my upbringing, actually. I was born in Scotland to two parents that-- born and bred in Scotland and grew up in Scotland. I spent the first six years of my life really living in France and then moved to Lawrence, Kansas, which was quite a cultural shift, but spent four years there. And it was great, actually, time in my life to be there, before moving to the East Coast, where I went to school and did all my medical training. So I'd had international experiences before, and I think that was an important part of my upbringing and something I sought for my kids, in the sense that it just immediately resets your sense of the world and makes you feel like a global citizen as opposed to just sort of more limited-- the community you're surrounded by. But it really wasn't until my experience as a fourth-year medical student at Brown that I had the opportunity to see health care in a low-resource setting and see that. And that was a very powerful experience professionally and personally. And as you said, it was the time when Joe Mamlin was really just dreaming up what the HIV response was going to look like, this nice institutional partnership that we'd set up in Western Kenya. But we set it up in the middle of the global pandemic. And true to our mission of responding and leading with care, felt a need to respond to the HIV pandemic. And that started really by-- was motivated by personal interactions that Joe had with some individuals who he saw firsthand come back to life, the Lazarus effect that has been reported. And that really spawned this whole response, changed my career and certainly my life, and had profound effects on my life. So that's a bit of who I am as an individual and how I got to where I am today. PAT LOEHRER: And we're going to touch on some of the work that you're doing now. But before I do, Bryan, tell us a little bit about and your background, where you grew up and how you got to where you are today. BRYAN SCHNEIDER: Thanks to you, and Dave as well, for having me on. And this will be an interesting perspective, because I think I'm coming on here as the patient this time, so it'll be a different view. But in contradistinction to Adrian, I am a pure Hoosier. I was born in the southern part of the state and raised there and then drove three hours north to Indianapolis, where I've set up for the last 25 years, and just been really lucky to be here at Indiana University. And Pat, you may not even remember this-- about 25 years ago, you were my formal mentor for med school, and so one of the influences and sticking around here along with some other real greats along the way. So have done, as you mentioned, breast medical oncology here in genomics and have had an absolute blast. So thanks for having me on. PAT LOEHRER: Oh, we love having you. And just as an aside, Bryan-- one is I think the world of you, and so proud of what you've accomplished. But Bryan's backyard actually was the home of Henry Lynch, and where he first described Lynch syndrome down in southern Indiana. And I think no greater tribute in his legacy than what you have done with precision genomics. It's really terrific. DAVE JOHNSON: Yeah. Maybe we'll have some time to delve into that. But actually, I'm curious, Bryan-- you mentioned that you've come on as the patient. My understanding is you've had firsthand experience with COVID, not just as a physician, but as the recipient of that wonderful new virus. Maybe you could tell us a little about that? BRYAN SCHNEIDER: Yeah, an interesting experience to be sure. So about 2 and 1/2 months ago, I tested positive for COVID and got really sick. Yeah, my three-year-old son had brought it home from his preschool and infected his older brother, who's almost 12, and then my wife and myself. And so was a really fascinating experience, I guess, and brought about some aspects to the virus that I had never really thought about. PAT LOEHRER: Now, Bryan, you also had COVID before, too. BRYAN SCHNEIDER: Yes. And the first time-- I was probably one of the very, very early cases and got really sick with it and lost my sense of taste and smell. I actually got one of the purple fingers, which I went to the ER for. I thought I was having a or something. And at the time, those weren't well-recognized symptoms. And that loss of taste and smell went months for me. So, yeah, I think I have frankly had the infection twice. The second time, though, was documented and certainly got really sick with the second one. DAVE JOHNSON: Can you elaborate on your second case? When you say you got really sick, was it a respiratory illness or were there other symptoms? BRYAN SCHNEIDER: Yeah, there were two aspects to it that were interesting. I think the first was physical. I got a sense of fatigue that I don't know that I have ever experienced before. It was one that I literally just could not get out of bed. And you know, I lost about 10 to 15 pounds from just being anorectic. And I'm not an overly thick human to begin with. But the big one was shortness of breath. And we had a pulse ox at home. My wife's a pediatrician, and I was sating in the high 80s. And I work out five or six times a week, so keep in pretty good shape, and I was stopping midway up the stairs to sit down, because I felt really tachycardic and just lightheaded. And so that degree of physical punishment is something like I have never expected or felt before. But the psychological part of it was really something I did not expect. And one part of that was an odd sense of guilt. I was getting texts and calls from a lot of friends checking on me, and many were baffled and asking, hey, did you not get vaccinated? Or what was going on with that? And so that-- it was a very odd sensation to me, because I, of course, had been vaccinated and I mask and all those sort of things. The other was one of real fear. I worried-- you know, luckily, I guess, our family all got infected around the same time, so we didn't have to think about quarantine. But I started wondering, could I have infected a patient? I take care of immunosuppressed breast cancer patients, before I was symptomatic. And then even after I came back to work, I had quarantined for quite some time, but I was really fearful. I would find myself double masking, washing my hands incessantly, and even holding my breath when I was trying to listen to heart and lungs during examination. So that sort of psychology was something I don't think I really expected with this infection. DAVE JOHNSON: How long did it take you to get beyond that, or are you beyond that part? BRYAN SCHNEIDER: Yeah. You know, I feel back to my baseline now. And I certainly don't worry about it on a day-to-day basis now. But my first clinic or two back was really hard for me, psychologically and emotionally. And part of me even wondered, should I profess to all my patients that I've had COVID? Or what things can I do to help protect them? And again, it was that mental aspect that I just didn't really anticipate prior to heading back to my clinic. DAVE JOHNSON: You know, this is eerily reminiscent of the physician who's had cancer who experiences extreme fatigue for the first time, chemotherapy-induced fatigue, after having described it many, many times before-- BRYAN SCHNEIDER: Right. DAVE JOHNSON: --and who has a guilt sensation in many respects as well. So quite the experience, for sure. PAT LOEHRER: Dave was talking about himself, by the way. BRYAN SCHNEIDER: No, I can only imagine. And you're right. We do try to paint a picture to patients about how things are going to feel, and it's amazing. When it's internalized or when you're feeling, it's-- it can often bring about a sense of, wow, I don't know that I-- I may have underplayed this to some of my patients in the past. And it really does provide some degree of empathy that's hard to capture if you haven't felt it. DAVE JOHNSON: So when I was on the wards, Bryan, I must confess, there were times when we walked into a patient's room with COVID who, of course, had not been vaccinated long after the vaccines were approved. Our professionalism prevents us from doing anything other than taking care of those people, but I'm wondering how you feel about caring for patients who have not been vaccinated or refuse to be vaccinated. BRYAN SCHNEIDER: Yeah. I mean, I think probably similar to a lot of people listening here today, it's a bit frustrating. And I think we all take care of patients who have a really tough diagnosis. And we're in the interesting field of giving patients medications that really immunosuppresses them, so we spend time counseling on the fact that you may get really sick or hospitalized or even die from neutropenic sepsis. And I think that is something that rests really hard with patients who are already dealing with a life-threatening diagnosis. And so now, trying to do that counseling in the face of a global pandemic like we haven't seen for a hundred years has really brought around a sense of duress and distress in my patients like I've never seen before. You know, I even had a patient who moved away from her family to be quarantined during adjuvant therapy, which I, of course, recommended against. But it really impressed upon me how big a deal this was. And so to see their frustration, and then in contradistinction, understanding that some people didn't want to pitch in to help-- it was very frustrating and honestly just made me very sad for people who I know were really struggling with this. DAVE JOHNSON: Actually, I had one more question to ask you. You mentioned coming back-- did you, in fact, share your diagnosis with your patients? I mean, I-- when I had cancer and came back, I made a pact with myself that I wasn't going to do that. But then I learned that the nurses were telling patients that I had cancer, and I found that it actually was helpful to share that diagnosis with many of my patients so that they could ask questions and feel that they had someone who really had experienced what they were either going through or about to go through. So I'm wondering how you've shared your diagnosis of COVID with patients, if at all. BRYAN SCHNEIDER: No, that's a great question. And I may have followed a similar pattern. At first I didn't. I didn't know what to do, to be frank. I didn't know if my saying that would make that patient, in that moment, more stressed out or worried, and I certainly didn't want to add to that. So I took it upon myself to try to make myself as safe to them as possible. But now that I've had a little chance to reflect on it, I have shared it. And I think for some of my patients, it's been good for them to hear what that experience was like. I think it's also-- Dave, as you probably know, I think it also reminds them we're human, too, and we experience some difficulty with physical health and I think in some ways it allows us to bond in a little bit deeper way. DAVE JOHNSON: I agree. PAT LOEHRER: I want to turn the attention over to Adrian now. Adrian, you're in a unique position, obviously one because of your experience in Kenya, and we want to hear about that, but also your responsibility for Indiana University. What some of the listeners may recall is that there was a decision made that you were part of that actually mandated that students in Indiana University be required to have vaccination before they came to school. We were in Kenya at the time when we heard that there was some consideration about that from the state legislature in terms of how-- mandating that. And eventually, this was a case that in which eight students took this case to cohort that eventually reached to Amy Coney Barrett, who decided to find in favor of Indiana University. It was a landmark decision here. But tell us a little bit about your experience on the leadership role of COVID and the impact that you see in terms of yourself personally and from the field of the university. ADRIAN GARDNER: Yeah. Thanks, Pat. I think it's really two different worlds in my mind, in some ways, although clearly linked by this global pandemic. You know, I was just finishing my eight-year stint, essentially, in Kenya in March of 2020 when we got the news that the entire world was about to be declared a level 4 by the State Department. And well, that-- I remember actually talking to Joe Scodro on the phone. And he's like, what the heck does that mean? That's not in our playbook of what we do when things happen and we need to bring trainees home and sort of-- PAT LOEHRER: Scodro being the lead counsel for Indiana University here. ADRIAN GARDNER: Thank you. Yeah, yeah. So for me-- I mean, obviously I was making a transition back to a US-based career in this position as the Director for the Center for Global Health. But you know, I had a dramatic change in my position, right? I mean, who is going to do global health operations in the middle of a pandemic? Well, nobody, because nobody was traveling. So we had really shifted all of our Kenya operations to a virtual support. We pulled all our trainees and long-term faculty back, initially. And my own position here is-- got pulled into a leadership role in Indiana University's response to the pandemic, along with three other physician leaders. And we all took on a different component of the response. So I was involved in the contact tracing, in part because we had some experience with contact tracing and global settings and tuberculosis and HIV. And while the transmission dynamics are obviously quite dramatically different and has different implications, but some of the principles around contact tracing were similar in the sense that contact tracing is not about really a stick, but it's more about extending a carrot and extending the support that allows you then to create an enabling environment-- and a quick phone call, in this case-- to allow people to identify what it is to quarantine and isolate effectively. To get to the Supreme Court issues and around mandates-- I think it was fairly obvious-- we were part of a restart committee that had been put together by the Dean of the School of Medicine, Jay Hess, and it was fairly noncontroversial among that group that we were going to need vaccine as we marched through this. And we immediately set up a lot of testing infrastructure and what we called mitigation testing at that point of asymptomatic individuals in addition to creating systems that enabled people to-- with symptoms, to enable testing very quickly and to get results back and to get that whole infrastructure in place. But it was pretty obvious to us-- it was a group of medical, public health, and ethics and legal folks-- that we were going to need a high level of immunity to get back to anything normal, right? And as we began planning for the summer and the fall of 2021, it was like-- it's a no-brainer. I mean, the only way you're going to get high levels of immunity, if you want to bring people back into the same classroom, if you want to have people living in dormitories, if you want to have them engage in the normal activities that college kids want to engage in, then you've got to have a very high level of immunity. And the only way to really achieve that is going to be through vaccine mandates. And again, it wasn't-- it didn't feel unprecedented, because you have to get a whole bunch of vaccines when you go off to college or when you go to elementary school. And that's really the only way to achieve that high level of coverage that allows us to not have a bunch of measles in our environment. And we still have mumps, despite high levels of coverage. But yeah, it felt weirdly noncontroversial. But of course, the whole politicization, I think, of the whole response to the pandemic made this more controversial. And clearly, there are people that feel very strongly about it. But I think this-- framing it in a context of personal freedom versus public good has not been particularly healthy for us as a country. I guess I'm not terribly surprised that the Supreme Court ultimately ruled against the preliminary injunction. I think the formal case is still pending, but it's maybe been overtaken by events, because now there are government mandates that are requiring vaccine or regular testing of just about-- lots of different industries and government employees and things. So I think it was important that we took a stand on this. And I think it has set a precedent, I think, for other universities. There were initially some hospital systems doing the same. But I think it's made it a lot easier to keep moving through industries and health systems with this kind of decision. PAT LOEHRER: Parenthetically, there's-- this week, they announced the-- we've reached over a million cases of COVID in Indiana. But the lowest county for infectious rate is actually Monroe County, which is where Bloomington is, where Indiana University is. And it's less than half of the rate of the state. And so I think kudos to you and the staff that have done this. Just maybe briefly, could you reflect on your experiences in Kenya, here in the United States-- lessons learned by you or by the university or by public officials about the contrast? I am reflecting now about a patient I saw today, that-- we were talking about the booster vaccine. And unfortunately, in Kenya, most people haven't gotten their first vaccine, either. So reflect a little bit about the global impact as you've seen personally. ADRIAN GARDNER: Yeah. So again, I think it's felt like two different worlds, but obviously struggling with the same thing, right? So I think on a global perspective-- so Kenya has-- Kenya got off to a pretty good start because they were kind of late to the game when it came to COVID, and they were able to jump on and learn from some of the lessons about physical distancing and shutting things down that actually enabled them to escape in the beginning. Of course, there was probably transmission going on behind the scenes that we weren't detecting, and even till now, the numbers that are officially reported are really just the tip of the iceberg. I think know that. Kenya has only reported 250,000 cases and just over 5,000 fatalities nationwide since the beginning of the pandemic. But there are serology studies that suggest that 50%, 60% of the population may have actually been infected-- at least, right? And that's based on blood donor studies and things. So I mean, I think some of the initial challenges, obviously, around access to PPE-- as we think about health care settings there, which are-- our partnership is based in, as you know. It's just the lack of infection control and the ability to even think about infection control because you're lacking space. As you know, Pat, in many of these wards in low-resource settings, there are two patients in every bed. And one might have active pulmonary TB and one might be getting chemotherapy for breast cancer. And it's less than ideal. But as you think about how to respond to that, it's pretty hard when you don't have any space, right? I mean, we did a lot here in terms of retooling space and utilizing space that was not being used and putting in negative pressure rooms where they were needed and this kind of thing that just weren't options in Kenya. One good news was that I think in Kenya, in particular, the testing capacity was able to get an early jump because the HIV infrastructure, PEPFAR, the President's Emergency Plan for AIDS Relief, had established seven regional laboratories that were obviously running HIV viral loads and so had PCR platforms. And they were able to rapidly retool those and convert them into COVID testing laboratories for PCR. So that was good, but then never really got to the same point where we need to get to, which is that it's readily accessible to everyone in rural regions and rapid testing in order to inform triage protocols [INAUDIBLE] patients and try to figure out how to develop that. So there's been testing available, but just not in the quantities that were sufficient. You know, I think we've been able to work across virtual platforms to share knowledge about management and clinical protocol development. That's been another success story. Certainly our partnership is longstanding and so has allowed those relationships that have withstood the test of nonpersonal interaction. And of course, the biggest elephant in the room now is this issue of vaccine equity, as you pointed out. So about 5% of the population in Kenya has been vaccinated. Part of that is vaccine access. Part of it is probability distribution infrastructure. Think about low resource settings-- many of them do quite well with vaccine delivery, but they're early childhood vaccines, right? So they have whole infrastructure around maternal child health that's set up to do this. There's not a lot of infrastructure for rapidly mobilizing 50 million adults to try and get them in for a two-shot series. So how do you do that? I mean, yes there are some community assets in terms of community health workers and things, but so far, at least, the vaccine quantities available have not been sufficient to allow that kind of infrastructure to really take over, at least in Kenya. But it holds promise, I think. But then they also are up against the same, I think-- some of the same challenges that we face here in terms of vaccine misinformation and lack of trust. This is an area where I think trust is really key ingredient in health systems, and I think we've seen it in our own inequalities that have been made very, very obvious in our own country and really, the issue globally. And it's not a new lesson. We knew it from Ebola and other very obvious infectious diseases that have resulted in high degrees of death because of lack of trust. When I have taken care of patients here and I've had those same experiences that Dave was talking about earlier, where you want to just ask the patient, so why didn't you get vaccinated? As an infectious disease provider, we've been called in to a lot of these cases, and I've taken the opportunity to ask a couple of times-- not in a judgmental way, but trying to set the stage and just-- what is it about the system? And a lot of-- some of it is misinformation. Some of it is this politicization and political bias. But some of it is just a very subtle mistrust and this notion that you don't feel completely welcomed or resected within the health care setting. And that's enough to just turn it off to this point where, eh, I'm just not ready to do that. And I think that's sometimes more subtle than we appreciate, but it has a huge impact. DAVE JOHNSON: We're getting close to the end of our time. I want to pivot back, if I may, just for a quick moment to Bryan. This may be an out of-- from left field type of question, but we learned a lot about early chemotherapy from the infectious disease world. We took some of the infectious disease principles and applied them in the early years of chemotherapy. Do you think there's much to be learned from a precision medicine standpoint from the COVID pandemic? What are you taking away from not just your personal experience but the larger experience, if anything? Or is that just-- is it just too early to say? BRYAN SCHNEIDER: No, I mean-- I think I've always admired the speed and efficiency with which breakthroughs have happened in infectious disease. And I mean, the idea of a brand new virus coming on board a couple of years ago and coming to the point where we are today shows, I think, real innovation, but the ability to get behind a question and, as a community, answer it well. And I think from that standpoint, that's something that all disciplines, including oncology, can learn. I certainly think we're seeing more and more intersection, too, with the way we think about treating cancer and its impact on immunity. And so certainly in that way I think there's real connections. But I do think some of the innovations that were brought about from the NCI with the vaccines are going to really also herald in things that will be game-changers in the world of oncology and therapeutics as well. DAVE JOHNSON: That's great. PAT LOEHRER: If I can throw in something, too-- I think, Dave, particularly as we talk about global health, many of the cancers that we see in the low-to-middle income countries are caused by viruses. One of the number one causes of cancer in sub-Saharan Africa is cervical cancer. We could eradicate that by getting vaccines out there. In terms of the lessons learned, I think the lessons learned in oncology is that we need to deal more with population health and with prevention than we do with the treatment towards the end of the life. And hopefully that will be a lesson that we can take home with us around the world. ADRIAN GARDNER: Yeah, and Pat, I think we do need to do better as a global community in terms of sharing vaccine and getting manufacturing up, and not just for vaccines but PPE and therapeutics. It's just not fair, the world we live in now. And at least we all know that and we take it for granted in some ways. But it shouldn't be this unfair, right? And that's been part of the problem globally, and it's part of the problem in the United States. DAVE JOHNSON: Yeah. PAT LOEHRER: But the tail end also is access to drugs for chemotherapy, too, and to have radiation available for all these patients. So it is-- this access is an important part of health equity globally. And I think it behooves all of us to be involved with this mission. DAVE JOHNSON: Well, again, we've come to the end of our time. And we want to thank all of our listeners, but most of all, we really want to thank Bryan and Adrian for a wonderful interview. We really appreciate your time and you sharing your experiences with us. Thanks again to the listeners for tuning in to Oncology Etc. This is an ASCO educational podcast. We want to talk really about anything and everything, so if you have an idea for a topic or a guest, we invite you to share that with us and email us at [email protected] So thanks again. And remember, Pat, I before E except after C. PAT LOEHRER: [LAUGHS] Well, I'll see you later, then. DAVE JOHNSON: No, wait a minute. Wait a minute. Eight, leisure, sovereign, weight, weird, foreign, vein, neighbor-- apparently it doesn't work. [LAUGHTER] My second-grade teacher taught me that rule, and it's just wrong. [MUSIC PLAYING] SPEAKER: Thank you for listening to this week's episode. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.
  • ASCO Education Podcast podcast

    Oncology, Etc. - On Leadership and Pearls of Life with Dr. Susan Desmond-Hellmann (Part 2)

    20:10

    In the second part of this Oncology, Etc. episode Drs. Patrick Loehrer (Indiana University) and David Johnson (University of Texas) continue their conversation with Dr. Susan Desmond-Hellmann, exploring the prominent leadership roles she held, from first female Chancellor at UCSF to CEO of the Bill and Melinda Gates Foundation and member of Facebook’s Board of Directors. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 11/18/21   TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. PAT LOEHRER: Hi, Everybody. I'm Pat Loehrer. I'm director of the Centers of Global Health at Indiana University, Melvin and Bren Simon Comprehensive Cancer Center. DAVE JOHNSON: And I'm Dave Johnson. I'm Professor of Medicine here at UT Southwestern Medical School in Dallas, Texas. So Pat, we're back for another episode of the award winning "Oncology Et Cetera." PAT LOEHRER: Just seems like last month we were here time, you know? Time just flies. DAVE JOHNSON: Exactly. Before we get started, you were telling me about an interesting book you were reading-- something about friends or something. Can you elaborate? PAT LOEHRER: Sure, sure, yeah. This book I picked up-- actually, my wife picked it up. It's called First Friends. It's written by Gary Ginsburg. It's a really interesting book. It was-- basically talks about-- it probably has about eight or nine presidents but the importance of having a friend that guides him. And these were people that were, in many ways, unelected people that were close to the presidents that helped change the face of what we see today, and some of them are stories of really good friends and some of them are, I think, opportunistic friends. But it gives you a background of people like Madison and Lincoln and Roosevelt and Woodrow Wilson. It's actually a fun read. DAVE JOHNSON: I'll definitely put it on my reading list. It sounds like a pretty exciting one. Well, speaking of influential people, we're really excited to jump back into our interview with Dr. Helman. In our last episode, we covered her early life and career, her work in Uganda, her views on global oncology, and her experiences in private practice and industry. In the next half of our interview, we'll learn more about her incredible career and her multiple leadership roles. Let's start by hearing about her time as chancellor of UCSF. PAT LOEHRER: Let me transition a little bit. What I'd like to do is talk a little bit about your leadership. One Of the next big roles you had, you became chancellor at UCSF, correct? SPEAKER 2: Mm-hm. PAT LOEHRER: And so as Dave said, I think you were the first woman in that role. SPEAKER 2: I was. PAT LOEHRER: You were a groundbreaker from that capacity. So now instead of working for people-- obviously, I understand that there's people you work for when you're chancellor too, but tell a little bit about that transition from industry back into academics and how that felt in the role of being a leader and then maybe the responsibility of being the first female chancellor. SPEAKER 2: There were parts of being the chancellor at UCSF, I would say most parts of it, that I just thought were fantastic. I loved being back at a hospital and clinics. Just the way the hospital and clinical enterprise at UCSF works, the chancellor is the board. And so once a month, you'd have neurology or cardiology come and tell you about what had happened, quality control, things that had gone on and I would have done that all day long. I mean, it was just so interesting. It was so important to run a great clinical enterprise that getting back closer to patients and medicine I thought was fantastic. The other thing was the educational enterprise, and UCSF, as you know, has medicine, pharmacy, dentistry, nursing. I always tell people, no undergraduates, no English majors, no marching band. And the other chancellors reminded me, no athletic director, which apparently is a very good thing. So UCSF is a very special and unusual place. And I loved the science. I would show up at research seminars and things like that as often as I could. So there were so many parts of being at UCSF that I thought were just off the charts great. The hardest thing about being at UCSF-- being the first female chancellor, I think, was challenging but not in ways that you might expect. I was used to being a woman leader in medicine and biotech, which was unusual. So being the only woman in the room, being the first, wasn't new to me. But the thing that was hard on our family was there are roles for the spouse of the chancellor that fit more neatly into more of a classic female role, hosting things. There was a tea party for the wives of the faculty that the wife of the chancellor typically had. And for some reason, Nick didn't think that that suited him. We sort of laughed about that. DAVE JOHNSON: He can't make tea? SPEAKER 2: He can't make tea to save his life. And he's a strong introvert, which made it worse. I will tell you, some of the under-recognized, underreported people in life are spouses of chancellors and presidents of universities. And talk about unpaid labor-- my goodness! And so we sort of struggled with how did Nick show up, what did that look like. Because we didn't have any role models for what that looked like. I still laugh that Bill Clinton said he would be First Laddie. So when you have a pattern recognition, life is easier. And then being one of 10 chancellors at the UC system, I struggled a little bit with the UC Regents just because it felt-- I became chancellor in 2009, and we had some fiscal realities that we were dealing with. And the pace of the UC Regents and the format of the UC Regents, I actually made a proposal for UCSF to kind of break off from the other 9. And that was not well-received, got me in the newspaper. And I did not do that again. People saw it as disloyal and not very smart. But all in all, I thought then and think now that our public universities are absolutely-- they're treasures in America. And I was really proud to be a part of it and hope that I had made a contribution. DAVE JOHNSON: Speaking of leadership, what was it like to be CEO of the Bill and Melinda Gates Foundation? What caused you to step away from chancellor to philanthropy? PAT LOEHRER: It's not a step down. It's not a step down, basically. DAVE JOHNSON: It is not a step down. SPEAKER 2: So I would say a couple of things. First of all, Bill and Melinda pushed me hard to take the job. I was not looking to change. My husband worked at the Gates Foundation for a couple of years on HIV. So they knew us, and they knew Nick better than me. But they knew both of us. We awarded Melinda the University medal at UCSF. And to my great surprise and happiness, she accepted and came. I later think that she was using that as a reason to talk to me about the CEO job, but she got a twofer. And I was really compelled by the mission. Who wouldn't be? I was really compelled by the mission and the chance to get back into global health after the experience I had had in Uganda. But I'll tell you, it is the ambition of the Gate Foundation, the scope of the Gates Foundation, the resources, and the need to get something done. I tell you, it is hard work. It is really hard work-- from China to India to all of the continent of Africa and then US education. Throw that in on top of things. So I was thrilled to be a part of driving the agenda and the mission. Some really talented people who are working very hard at the Gates Foundation-- I was surprised, especially on US education, with the amount of pushback. And I worked really hard to be successful at working with Bill, who's known as a tough character and lived up to that mutation. DAVE JOHNSON: Good to know, just in case he calls Pat or me. PAT LOEHRER: Yeah, yeah, I'm not going to get a medal at UCSF either. So that's a-- DAVE JOHNSON: You never know, Pat. PAT LOEHRER: It's a non-starter. And this may not apply to you, but there's a lot of maybe disproportionate number of women who feel they suffer from this imposter syndrome. To be honest, Dave and I have talked about that. We both feel in that syndrome too. But along the way, I mean, if you think about growing up in Reno, Nevada, and suddenly now being a chancellor and head of the Gates Foundation, the National Academy of Science, was there ever this sense of the, wait a minute, you know, what's going on? Is this real? SPEAKER 2: For me, there has always been that sense. There has always been that sense, and I look at it as I hope there always will be that sense-- that the kind of need to demonstrate your value. And there's a part of the imposter syndrome that is humility and not overestimating what you can do. And so on my best days, I think that leads me to say I've got to work with really terrific people. My job is to bring out the best in others. If I lead, it's because there's a great thing we're going to accomplish, and I can help people see where we're going together. And so I definitely have had imposter syndrome. But the one thing that I probably overused and kind of grew to like too much was the thing of people underestimating me and then proving them wrong. That gets a little wearying after a while. It's like, OK, we're going to waste some time while you decide whether I'm worthy or whether I can do this. And let's not waste that time. Why don't you assign to me-- give me some confidence, and I'll live up to that. And I mentioned Art Levinson was my boss for most of the time I was at Genentech. And he had no time for imposter syndrome. He was like, look, how many promotions do you have to get before you think, OK, I can get this done? He thought that was sort of-- he just didn't have time for it. We have things to do, and he had jobs to get done. And one of the things I loved about him is he would constantly push me to say, you're capable of more than you think you are, which I think is the sign of a fantastic manager, which he was and is. And so I've tried to push myself to do that. And the thing is, like, you can do this. Come to me for help. We'll make sure you succeed, but don't underestimate yourself. And I think that's a consequence of imposter syndrome is both wasting time proving yourself and not taking on something that you think, actually, let me give that a try and stack the deck in favor of succeeding. And so I think that's the thing that-- there's a certain fierceness that I've always had that I like about myself that, like, of course we will succeed. Failure is not an option. Of course we will succeed. And I think that comes from working on things that I value a lot and care about a lot. PAT LOEHRER: You have been on a number of different boards, including Pfizer as well as Facebook. And in that capacity, you've seen a lot of leaders. Can you talk a little bit about the strengths and the weakness of various leaders as well as serving on the boards and the capacities of the different companies? SPEAKER 2: Yeah, well, first, let me say I know ASCO is actually a really good about being careful about conflicts of interest and things like that, and I am too. So when I became chancellor at UCSF and then CEO at the Gates Foundation, I avoided being on life sciences boards. And so I got asked a lot by Biotech and pharma boards to be on their boards. Initially, I joined Procter Gamble's board, where I served for, I think, about six years. And then I joined Facebook's board. And those were both fantastic experiences. And I actually joined the boards for two very different reasons. One, P&G's board, I wanted to learn about branding and consumers. And I felt like in medicine, I didn't really learn about consumers or branding as much as I needed to or might. And then Facebook's board I joined because as Dave mentioned, I was with Charles Sawyers. We wrote the precision medicine report for the National Academy. And I really love-- to this day, I love the concept of using the social network to connect people. There was sort of an infamous story or famous story-- it's actually a good story-- of patients with a certain form of myeloma who found each other on Facebook and went to Genentech and said, make a new medicine for those of us with this genetic abnormality. And we'll all enroll in a trial. And so these connections to me felt really powerful on precision medicine. And so getting to work with CEOs at Procter and Gamble, the CEO Mark Zuckerberg at Facebook, I do see the really different attributes of leaders. But when you're a board member, you see those attributes of leaders with a very different lens. What's the return to shareholders? How does the community think about them? What's the impact-- and increasingly for Facebook, what's the impact on the world? What's the impact on our social discourse and our ability to have a free and fair election? A lot of those things became much more operative on the Facebook board while I was on the board and really tough social issues that continue to this day. DAVE JOHNSON: Yeah, so we could go on for another hour, hour and a half, but I have one question to ask you which may seem a little bit silly in retrospect. But if you could look back on your youthful self at 21 or 22 knowing what you know now, with all the things that you've done during the course of your career, what advice would you give yourself? And perhaps I'll addend that by saying what advice would you give particularly to young women in the medical profession who are trying to balance that work-life balance that everyone talks about and worries about and struggles with, quite frankly. SPEAKER 2: I'll give you one thing I should have done better and one thing that I think I did well. So the advice on the one thing I should have done better, I think slow down a little bit and take a bit more time for fun and enjoyment. I was extremely worried about money when I was in college, and being number two of seven-- every summer, I worked. I remember at one point in medical school, I had three weeks off, and I got a job for those three weeks at a deli making sandwiches. And I went to college for three years, crammed it into three years so I wouldn't have to pay for the fourth year. So I just think that I could have taken on more loans. I could have done some things to just dial it down a bit because you don't get those years back. And that's such a great time of your life when you're 21, 22, something like that. So I wish I'd have just slowed down a bit and not been so driven for those seven years of university and medical school that I really just either worked or studied all the time. The thing that I feel like I did well, and I would say this to anybody who's going into medicine, is there's so many opportunities. There's so many wonderful things to do. But whoever your spouse is, whoever your partner in life is, take the time and energy to make sure that's the right person for you. I feel so blessed. Actually, my husband, who I've mentioned several times in this discussion, Nick, was my roommate in San Francisco when I was an intern, like real roommate. And we've been roommates ever since. And we're very compatible. He's one of seven kids too. It's another Catholic school kid. And we just have fun together and support each other. And there's no way I could have taken these crazy jobs or done the kinds of things I've done without Nick. So having a wonderful, supportive partner makes everything better. DAVE JOHNSON: That definitely resonates with Pat and me. We're both very blessed to have wives and spouses of, for me, it's 52 years. I can't remember, Pat. Yours is close. PAT LOEHRER: I had my first date with my wife 50 years ago, yeah. DAVE JOHNSON: Yeah. SPEAKER 2: OK, so you guys know what I'm talking about. PAT LOEHRER: Absolutely. DAVE JOHNSON: Yeah. PAT LOEHRER: Yeah. DAVE JOHNSON: Go ahead, Pat. PAT LOEHRER: I was going to ask a question that you probably may have already answered there, but Bob Woodward just came out of an interview with Colin Powell. One of the last questions he asked him was if he could reflect on that one person that was a moral compass for him. And so for you, that one person, alive or dead, that has been not the most powerful person you've met but the one that's really influenced you the most in terms of giving you direction, who would that be for you? SPEAKER 2: Probably, if I look at through line the entire time I've been alive, it would be my dad. He had the ability to look at a room and find the person who was struggling and go over to them. And I really loved that about my dad. PAT LOEHRER: I love it. DAVE JOHNSON: One last question. So we're at the top of the hour, and I know you're a very busy person. Pat and I love to read, but we're also documentary fiends and whatnot. We're interested. What have you read recently that really resonated with you? Do you have a recommendation for us? SPEAKER 2: I will say during the pandemic, I've gotten back into reading biographies, which I love. DAVE JOHNSON: Yeah. SPEAKER 2: So I did the Caro, Lyndon Baines Johnson, which, Master of the Senate is really good. But my favorite book of the last two years is The Code Breaker, Walter Isaacson's book about Jennifer Doudna. DAVE JOHNSON: Yeah. SPEAKER 2: One of the things I love about Walter Isaacson is he teaches you science through his biographies. Like, I think I understand relativity based on his Einstein biography, which is great. But The Code Breaker is really super good. DAVE JOHNSON: Yeah, we both read it. We couldn't agree with you more. PAT LOEHRER: Love it. Love it. DAVE JOHNSON: So Sue, again, it's been a real honor to have you as our guest, and we really appreciate the time you've taken. Thank you so much, and we hope you enjoy the beautiful weather in Alamo California, and I hope it does turn green and the rain continues for you. SPEAKER 2: Thank you so much. It's been my pleasure. Thank you both. DAVE JOHNSON: Take care. SPEAKER 2: Bye. DAVE JOHNSON: I want to take the moment to thank our listeners for tuning in to "Oncology Et Cetera," an ASCO educational podcast where Pat and I really will talk about anything and everything. So if you have an idea or a topic you'd like to share with us and like for us to pursue, please email us at [email protected] Thanks again, and keep in mind that Pat is a giant in oncology, but he's a short instructor. Thanks, everybody. SPEAKER 1: Thank you for listening to this week's-- to make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.
  • ASCO Education Podcast podcast

    Cancer Topics - New Therapies for Lymphoma (Part 2)

    20:48

    In the second part of this ASCO Education Podcast episode, Dr. Sonali Smith (University of Chicago Medicine) and Dr. Paolo Strati (MD Anderson Cancer Center) discuss the application of new therapies for mantle cell lymphoma and follicular lymphoma through examination of challenging patient cases. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 11/15/21   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] SONALI SMITH: Hello, and welcome to part 2 of ASCO Education Podcast on New Therapies for Lymphoma. My name is Dr. Sonali Smith, and I'm a hematologist and medical oncologist specializing in lymphoma and clinical trials for lymphoma. I am also the Elwood V. Jensen professor and chief of the Hematology and Oncology section at the University of Chicago. PAOLO STRATI: Hello to everybody. I'm Dr. Paolo Strati. I'm a hematologist, and medical oncologist, and assistant professor in the Department of Lymphoma and Myeloma and in the Department of Translational and Molecular Pathology at the University of Texas MD Anderson Cancer Center in Houston, Texas. In part one of this podcast episode, we discuss recently approved therapies for diffuse large B-cell lymphoma. And today, we will be exploring instead new therapies for follicular lymphoma and new therapies for mantle cell lymphoma. SONALI SMITH: Wonderful. So we are going to start off today with a discussion about a patient case. The individual is a 55-year-old woman with previously untreated follicular lymphoma, low-grade advanced stage, and low tumor burden, and low FLIPI. She was diagnosed three years ago and had observation but more recently developed a 7-centimeter retroperitoneal mass with impending ureteral compression and no PET/C concern for transformation, specifically with an SUVmax of 5.3. Despite this radiological finding, the patient had a performance status of 0, no symptoms, no significant comorbid health conditions, and was given R-CHOP time six cycles, followed by achievement of a CR. She was then observed, but, unfortunately, 18 months later, the PET/C showed diffuse low FDG-uptake adenopathy, and a lymph-node biopsy was repeated. This showed a follicular-lymphoma relapse. So Dr. Strati, tell us a little bit about your approach to follicular lymphoma in the initial setting. Do you consider GELF criteria? And how do you select second-line therapy in this patient? Does the early progression of disease within 18 months-- she falls into the category of POD24, or the Progression Of Disease 24 months-- how does this affect your treatment choice going forward? PAOLO STRATI: Thank you, Dr. Smith. Those are all very good questions. So going to your first question-- we typically use GELF criteria, as you know, developed in France now many years ago, most of the time of initial diagnosis. And that's to determine whether a follicular-lymphoma patient does, indeed, have an indication for treatment. And this criteria, as you know, are based on lymph node size and number, oragnomegaly, cytopenia. However, it's still debated whether this should also be applied at time of relapse. And in this particular case, the patient, as you said, had what we call a POD24, or progression of disease within 24 months from initiation of chemoimmunotherapy. Given the suboptimal outcome of these patients, I think that it will not be unreasonable to treat these patients even if they don't formally meet GELF criteria-- so even if they don't have formal indication for treatment at time of relapse. Once the decision is made, standard second-line options for patients with follicular lymphoma currently include chemoimmunotherapy So if the patient received R-CHOP in frontline, it would be BR. But if they receive BR in frontline, of course, R-CHOP, but also, immunotherapy with R-squared-- so Rituximab, Revlimid-- or lenalidomide, a single-agent anti-CD20 monoclonal antibody, obinutuzumab, which is specifically approved by the FDA in the United States for rituximab-refractory follicular-lymphoma patients, and in very selected cases-- and this is still open for debate-- a high-dose chemo with a platinum-based agent followed by autologous stem-cell transplant. We don't know at this time what's the ideal second-line strategy for patients like the one that you described in your case-- so a follicular-lymphoma patient with POD24. And to this regard, all are very eagerly awaiting the results of an ongoing SWOG trial, 1608, which is a randomized phase II study comparing in second-line chemoimmunotherapy, immunotherapy, and also, [INAUDIBLE] kinase inhibitor for this patient with POD24. Finally, one thing which I think is important to consider is that even if R-squared is not currently approved by the FDA in the frontline setting in the United States and, actually, is not approved at all in Canada, in Europe as a frontline treatment, in the United States, it's possible to use it in frontline thanks to existing guidelines. And over the last few years, its frontline use in our country has actually meaningfully increased. This is creating a new clinical scenario that we never met before. And there are no standard second-line options currently established for these patients, patients who receive frontline R-squared, emphasizing the need of translational research to understand more of the biology of patients who relapse after frontline R-squared but also, emphasizing the need to mostly look into clinical trials when these patients, unfortunately, experience a relapse. SONALI SMITH: Yes, thank you, Dr. Strati. I agree. I think that it is the way that frontline follicular lymphoma and in the relapsed setting exists is that we have a toolbox and no real clear data on how to personalize the therapy. So your comment about needing some better translational work to fine-tune the clinical trials is really important. So for this patient, though, she did receive R-squared for 12 cycles and achieved a complete remission after six cycles. 12 months later, a PET/CT showed diffuse, low-level adenopathy, "low level" meaning low uptake on a PET scan. And she had another lymph-node biopsy. This showed persistent follicular lymphoma. So now how do you select your third-line option knowing that we have biologic therapy, as well as cellular therapy, available to this patient? PAOLO STRATI: So going back to the metaphor that I used before, we have a very nice toolbox, often third-line. But also, in third-line, there's really no strong, robust translational data to drive us when it comes to treatment selection. Agents currently approved by the FDA in the United States as a third-line standard option for patients with relapsed/refractory follicular lymphoma include, as you alluded, [INAUDIBLE] kinase inhibitors, currently three-- copanlisib, duvelisib, and idelalisib, and an EZH2 inhibitor called tazemetostat. The three [INAUDIBLE] kinase inhibitors currently approved in third line have very similar efficacy with a response rate of 50% and a median progression-free survival of about 10 months. And the selection among the three is typically based on toxicity profile, which is more on the autoimmune side for duvelisib and idelalisib and more on the metabolic side with hyperglycemia and hypertension for copanlisib. Also, one element that, in my experience, is typically used to select one of these three is the route and the frequency of administration because we have to remember that idelalisib and duvelisib are both given orally twice a day, whereas copanlisib is given intravenously three times a month. And so, of course, different patients may have different preferences. As a matter of fact, though, the use of [INAUDIBLE] kinase inhibitors for relapsed follicular lymphoma in the United States and I would say, also, in other countries, is quite limited, mostly due to toxicity and relatively limited efficacy. Tazemetostat, the EZH2 H2 inhibitor that I mentioned previously, has a response rate that can vary between 30% and up to 70%, significantly higher in patients who do have a documented EZH2 mutation. But the median progression-free survival is about a year, no matter whether the mutation is present-- so not that different from [INAUDIBLE] kinase inhibitors in the same setting. Of interest, given the short duration of response, we may consider these agents as a bridging therapy for follicular-lymphoma patients. We [INAUDIBLE] proceed with CAR T-cell therapy because, as you mentioned in your question, CAR T-cell therapy, and specifically, Axi-cel, has been recently approved by the FDA as a third-line option for patients with relapsed/refractory follicular lymphoma based on results from the ZUMA-5 study. It's important, however, to emphasize that Axi-cel has shown better efficacy and safety data in follicular-lymphoma patients as compared to large B-cell lymphoma patients than we discussed in the previous episode of this podcast. And, as such, Axi-cel may potentially represent a curative option for patients with follicular lymphoma, a condition that, historically, has been considered incurable. Tisa-cel and other CAR T-cell products targeting CD19 currently approved by the FDA for large B-cell lymphoma but not yet for follicular lymphoma, may also be soon approved by the FDA for patients with follicular lymphoma based on the ELARA study. And we're all eagerly awaiting the results of this study and, potentially, its approval in the next few months. SONALI SMITH: That's great to hear. And, hopefully, we will continue to have more options, including more cellular-therapy options for patients. So this particular patient proceeded with the standard of care Axi-cel. That went quite well. There was only grade 1 cytokine release syndrome, no neurotoxicity. And the patient achieved a complete remission on both the day-30 and the day-90 PET/CT. Unfortunately, there was relapsed six months later. So what standard options are there at this time? And would you consider an allogeneic stem-cell transplant at this point? PAOLO STRATI: So I have to say that, based on some of my data, I'm not surprised this patient did quite well in terms of safety, and I'm very sorry to hear that was one of those few patients who relapsed after an initial complete remission after Axi-cel. In fourth line, our options are a little bit more limited. The FDA has recently approved in fourth line, for patients with relapsed/refractory follicular lymphoma, a new [INAUDIBLE] kinase inhibitor called umbralisib. [INAUDIBLE] umbralisib response rate is quite similar to other [INAUDIBLE] kinase inhibitors, about 50%. However, the median progression-free survival that, as I mentioned before, is about 10 months for the [INAUDIBLE] kinase inhibitors currently improving third line instead has not be reached yet two years for umbralisib. And also, the toxicity profile seems to be more limited, similarly to idelalisib and duvelisib, more on the autoimmune side. Therefore, definitely umbralisib would be an interesting option for the patient case that you described. As for your second question, the possibility to use allogeneic stem-cell transplant for patients with relapsed/refractory follicular lymphoma, retrospective studies have shown the allogeneic transplant is effective in follicular-lymphoma patients, particularly those with POD24, like the patient you described in the scenario. But the transfer-related mortality is significant and needs to be taken into consideration. But most important of all, as CAR T-cell therapy has been approved for follicular lymphoma very recently, we really have no data regarding the use of allogeneic stem-cell transplant in follicular-lymphoma patients who relapse or progress after Axi-cel and CAR T-cell therapy in general. This last statement really applies to any approach as, again, Axi-cel has been approved for follicular lymphoma only within the last 12 months. And this, once again, emphasizes the importance of translational research and clinical trials for these patients. And as such, I think that, along with umbralisib, there is a standard option. Clinical trial's definitely the best option for patients with follicular lymphoma whose disease is either refractory or relapses after CAR T-cell therapy. SONALI SMITH: Yes. Thank you for these insights, Dr. Strati. I agree. The post cellular therapy, or the post CAR-T space is a very challenging situation, and I appreciate your perspectives. So as an update, this patient received umbralisib for six months and had an initial response with a partial remission but eventually progressed and then proceeded to a clinical trial, now on a novel oral-immunomodulatory agent and has been in a complete remission for four months. PAOLO STRATI: That's great to hear. And I hope that this remission will be durable, emphasizing, again, the importance of clinical trials for patients with lymphoma in general, and particularly, those who relapse or are refractory to standard treatments. It was very interesting to listen to this case. Thank you for asking your question, Dr. Smith. I'm going to ask your opinion now about a second case. This is a 67-year-old man with diabetes that has a long-lasting history of rectal bleeding, for which he underwent a colonoscopy in 2016 that revealed hemorrhoids and scattered polyps that were not malignant on biopsy. However, as part of routine follow-up, a colonoscopy was repeated five years later, and this, unfortunately, showed diffuse nodularity of the colon with several areas of ulceration. Biopsy of the nodules showed a mature B-cell lymphoma, CD20 positive, CD5 positive, BCL2 positive, SOX11 positive, but negative for CD10. FISH testing confirmed a translocation 11;14. There was no evidence of TP53 mutation, and Ki-67 was 40%. So Dr. Smith, what do you think about the overall potential histological diagnosis? And how do you approach this patient in terms of staging and prognosis discussion? SONALI SMITH: Yes, so this poor patient, with long-standing rectal bleeding-- I mean, this can happen. It's not a very common presentation for mantle cell lymphoma, but we know that mantle cell lymphoma is very likely to involve the GI tract and can often be extranodal. In terms of the histology itself, this is very classic. The co-expression of CD20 along with CD5 is only seen in CLL and mantle cell lymphoma. And in this case, the mantle cell lymphoma's confirmed by SOX11 positivity, CD10 negativity, and then, also, of course, the FISH [INAUDIBLE] translocation of 11;14 with a cyclin-D1 overexpression. When it comes to prognosis in mantle cell lymphoma, there's a number of different prognostic indices, but the two biologic features that I think are most important are P53 status, as well as the proliferation rate. Patients who have a TP53 mutation typically have chemo-resistant disease. And we have no really good approach in terms of how to treat these patients the best. PAOLO STRATI: Thank you, Dr. Smith, for outlining the diagnostic and prognostic approach to patients with mantle cell lymphoma. You alluded in your answer about the regenerative treatments, so I wanted to ask you, how do you, in general, treat patients with mantle cell lymphoma and, more specifically, this case. And also, we keep dividing patients with mantle cell lymphoma in transplant-eligible and ineligible, but the big question is, do all patients who are transplant-eligible need transplant? And what's year overall approach to this major dilemma? SONALI SMITH: Yes. That's a really good question. The general approach to treatment for mantle cell lymphoma is based on the concept of fitness and age. So we end up dichotomozing patients into one of two groups. They are either young and fit, or they are older and unfit. And, of course, this is somewhat controversial because age itself is just a number, and there is significant variability based on function and other medical conditions. Complicating that further is that many clinical trials have used 65 as the arbitrary cutoff between young and old, whereas some transplant studies have actually gone all the way up to age 70. So if I focus on the fact that this is a 67-year-old man who has no real significant history and clearly has a disease that needs treatment, my general approach has been to follow the younger-and-fit approach. And as you mentioned, the historical approach to this has been to think of treatment in three phases. There is induction, there's consolidation with a high-dose chemotherapy and autologous stem-cell transplant, and then there is maintenance rituximab for three years, which has been shown to have a survival advantage. But your question-- I think there are many unanswered areas when it comes to approaching a patient who is going to be treated with an aggressive multimodality approach. So first, in terms of the induction itself, there is data that cytarabine-based regimens likely achieve a deeper minimal residual disease state than aklylator-based therapy. And so cytarabine-containing regimens have really become the standard of care against which other regimens are compared. That being said, there was at least a SWOG study that randomized patients between BR and hyper-CVAD and found that BR was a sufficient type of induction. And some of this controversy led to an ongoing Intergroup trial, which is EA4181, that takes patients with newly diagnosed mantle cell lymphoma, previously untreated, like our patient, and randomizes them to bendamustine, rituximab with or without cytarabine and with or without a BTK inhibitor, in this case, acalabrutinib. So outside of a clinical trial, I would use a h based induction regimen, but I have preferred to put most patients onto that. But your second question, which is, do all patients need high-dose chemotherapy and autologous stem-cell transplant, is really important. This is associated with a need for inpatient admission, high-dose chemotherapy with subsequent late toxicity. And remembering that mantle cell lymphoma remains an incurable disease, the question is whether or not all patients should get this. So to address this, there is the EA4151 trial, which is also being done through the United States Intergroup. And this is using a very unique minimal residual-disease assay to randomize patients to either transplant plus maintenance or maintenance alone. And so this is a next-generation sequencing test. And if patients have a negative MRD status at a very deep level, then patients will get randomized to one of those two arms, whereas if they have minimal residual disease that is detectable, then they will go ahead and get the standard of care. So for this patient, he opted to be on the clinical trial and was randomized to BR, plus cytarabine, plus acalabrutinib. But outside of a trial, I really would have considered intensive induction, including the Nordic regimen that includes high-dose cytarabine, followed by transplant and maintenance rituximab. Now some may argue with me that this person is 67 years old, and the Nordic regimen is quite intense. And I think this is where some of the art of medicine may come in. And, hopefully, we can have some type of assessment tools to better predict who can tolerate intensive induction. But I'm quite impressed by some of the transplant data that do lead to seven- and 10-year remissions in some cases. Of course, this new trial will tell us whether or not we're overtreating many of the patients, particularly based on their MRD status. PAOLO STRATI: Thank you, Dr. Smith. It was very helpful. I think you outlined really well how challenging it can be to treat patients with mantle cell lymphoma and how important it is to tailor treatment based on biological but also, patient-related data. This is all that we have for today. Thank you, Dr. Smith, for a very delightful conversation. It's been very helpful to review together today the treatment of patients with follicular lymphoma, and mantle-cell lymphoma, and safety and efficacy of novel therapies for these patients. Thanks, everybody. And, particularly, thank you to all the listeners who tune in to this episode of the ASCO Education Podcast. And thank you, Dr. Smith, for your time. SONALI SMITH: Thank you. It was such a pleasure to have this conversation today. [MUSIC PLAYING] SPEAKER: Thank you for listening to this week's episode. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.
  • ASCO Education Podcast podcast

    Oncology, Etc. – On Leadership and Pearls of Life with Dr. Susan Desmond-Hellmann (Part 1)

    25:49

    Part one of this two-part Oncology, Etc. episode features an inside look at the amazing career of Dr. Susan Desmond-Hellmann (spanning from early AIDS research in Kenya and drug development at Genentech, to serving as UCSF Chancellor and CEO of the Bill and Melinda Gates Foundation). Hosted by Drs. Patrick Loehrer (Indiana University) and David Johnson (University of Texas). Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 11/04/21   TRANSCRIPT [MUSIC PLAYING]   SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. DAVE JOHNSON: I'm Dave Johnson. I'm a Professor of Medicine here at UT Southwestern Medical School in Dallas, Texas. PAT LOEHRER: I'm Pat Loehrer. I'm Director of the Centers of Global Health at Indiana University Melvin and Bren Simon Comprehensive Cancer Center. DAVE JOHNSON: We have a remarkable guest today, Dr. Susan Desmond-Hellmann. She's like the Wonder Woman of oncology who's done many amazing things during the course of her career. It would take us more than an hour or more just to read off her CV. But very briefly, Dr. Hellmann is a graduate of the University of Nevada, Reno where she got both her Bachelor and her medical degrees. She received her medical training at the University of California, San Francisco. And then after that, did something really interesting. She went to Uganda for a couple of years and worked at the Ugandan Cancer Institute where-- maybe we can delve into that a little bit later during the course of this discussion to find out what she did while she was there. After which, she also did a couple of years of private practice and then joined industry, first at Bristol Myers, where she was instrumental in the development of a very important drug for a lot of different diseases-- paclitaxel And then in the mid-90s, she joined this little biotech company called Genentech, first, I think, as a clinical scientist. But over the course of a few years, she rose to the level of president of product development and really was instrumental in developing many drugs, including trastuzumab and bevacizumab. In fact, I think it was Forbes magazine that named her as one of the world's seven most powerful innovators, which we have to ask her more about that later, about being a powerful innovator. After really a stellar career in the industry, she then went back into academics. She became the chancellor of the University of California, San Francisco, and I believe the first woman to hold that position, if I'm not mistaken. During her tenure, many remarkable things happened at UCSF, including growth of their campus in the Mission Bay. She was responsible, with a committee put together by the National Academy of Sciences, of producing the report entitled Toward Precision Medicine, Building the Knowledge Network for Biomedical Research and a New Taxonomy of Disease. In March of 2014, I believe it was, she took yet another position, this time in the world of philanthropy, where she became the chief executive officer of the Bill and Melinda Gates Foundation, a position she held until December of 2019. And that's certainly something we want to ask her about. Dr. Hellmann has many, many accolades. I can't list them all, but she's a member of the Biotech Hall of Fame, the American Academy of Arts and Sciences, the National Academy of Medicine, and she's even received an honorary science degree from Princeton University. They won't even invite us to the campus, Pats. I'm not sure what it takes to get an honorary degree, but Sue, welcome to Oncology, Etc. And thank you so much for agreeing to this interview. SUSAN DESMOND-HELLMANN: Well, thank you for having me. I'm really glad to be here and look forward to our conversation. DAVE JOHNSON: Pat, why don't you ask the first question. PAT LOEHRER: So Sue, if you could tell us a little bit about yourself from birth until your early career and what shaped your early directions. SUSAN DESMOND-HELLMANN: Well, I'm actually a California native and grew up in Reno, Nevada, thus the University of Nevada connection. I'm one of seven children. I'm number two. And my affinity for science and medicine and all things regarding patients came from my dad, who was a retail pharmacist. And that's how we moved from California to Nevada. My dad and his partner Jim opened up one of those Rexall Owl drugstores-- if you ever remember those with the owl picture-- and were partners for many years, ran a pharmacy in Reno, Nevada which, when we got there, was a really small town. And I often chuckle when people say, oh, there's something sort of funny about growing up in Reno, Nevada. Did you go to casinos all the time? The fact of the matter is that my parents were very strict disciplinarians. We weren't allowed to work in the casinos as summer jobs, much less go to the casinos. I went to Catholic school for 12 years. Going to college was the first time I didn't wear a uniform to school, which was funny. But both my values and my passions came from worshiping my dad and the contributions he made to people feeling better. PAT LOEHRER: Love it. Love it. DAVE JOHNSON: It's fantastic. May I ask-- I presume you chose to go to UCSF for your medicine training because of your California connection. Is that right? Or was there other reasons? SUSAN DESMOND-HELLMANN: There were two main reasons. One is UCSF was far and beyond my number one choice because of its reputation. And when I interviewed there, I just was so astounded that I recognized the names of my medical textbooks among the faculty. That was a big deal for me. Holly Smith was a chair of medicine. I mean, it was the dream to go to UCSF. My dad was born and raised down the street from UCSF. And my grandma still lived there. And so, for me, it was also-- being the first time I had been away from home-- it was close enough to Reno that it wasn't crazy to drive back for the weekend. So a little bit more close to home and much more importantly, for me, the mecca where I would just get to be around so many talented people. PAT LOEHRER: When you were there, it was really at the early times of the AIDS pandemic. And there is some wonderful people there that I'm sure you interacted with, included Paul Volberding and the other group. So tell me a little bit about that influence. And that probably led, in part, to the transition to Uganda. But tell us a little bit about that part of your story. SUSAN DESMOND-HELLMANN: So my time at UCSF, first of all, I think it's, especially being in the midst of COVID-19, it made so many of us recall what it was like to be in San Francisco in 1982. It was really exhausting and terrifying to be a health care provider when so many of your patients-- first of all, they died quickly before antiretrovirals. But there was such a lack of understanding of what was going on initially. And so the medical program at UCSF, like a lot of programs of its nature, in New York, LA, led to Paul Volberding, Don Abrams, Laurie Kaplan, a lot of colleagues-- the oncologists became AIDS doctors and oncologists, because of Kaposi sarcoma and lymphoma and other maladies. And I remember I did an additional year as chief resident. And one of our concerns was whether or not the medical residents were overweight HIV and underweight kidney disease and hypertension. And there was a concern that people might not come for the residency because they were worried about catching AIDS. I mean, we were part of a study to test us. And happily, unless you had a needle stick, you really weren't at great risk. But the residency was very much influenced by that. I was very much influenced by that I had a lot of passion for caring for the patients. I think I had a lot of empathy for what they were going through. And think about this, go home and tell your parents you have HIV. And by the way, they didn't know you were gay, because a lot more people were closeted in those days. That's a really tough set of circumstances. So by the time I was an oncology fellow and then a faculty member, I saw, really, all the patients at UCSF at the University Hospital who had AIDS-related cancers. That became my specialty. And I was funded by the California State Task Force on AIDS to study Kaposi sarcoma. But when the Rockefeller Foundation came to UCSF to ask them to study heterosexual transmission of HIV, the late Merle Sande and Dick Root asked my husband, who's an infectious disease doc, and I to move to Uganda and accept this Rockefeller grant and study heterosexual transmission of HIV and Kaposi sarcoma. And I actually think it's a bit of a funny story. But it was less funny then, because I was so uncertain. I had never been east of Chicago at that point in my life. But we flew and moved to Uganda. So I became a global citizen quite quickly. And it was both the most important experience that my husband and I had had in medicine and life. And to say it was challenging would be an understatement. I mean, we did not have consistent electricity or running water. And we had this multi-page grant where we were supposed to do ELISAs and Western blots. It was a little crazy, but we got some things done and that was the important thing. DAVE JOHNSON: So Pat's never been further between Indianapolis and Chicago. So he resonates with him. [LAUGHTER]   DAVE JOHNSON: So you were there how many years? You were there two years, I think. SUSAN DESMOND-HELLMANN: Two years. DAVE JOHNSON: And did you accomplish the things that you set out to do while you were there? Or how did that go? SUSAN DESMOND-HELLMANN: We worked with our Ugandan colleagues and really transformed what you could do at Uganda Cancer Institute at the TB clinic in collaboration with folks from Case Western Reserve and for the AIDS program. So by the time we left, things just were dramatically better and different. We also did a lot of teaching, a lot of patient care. And so there was a service element to what we did, which was really essential that that be part of it. I had the opportunity, when I was at Gates Foundation in 2019, to return to Uganda. And the one thing you got at Cancer Institute, which was founded by NCI-- our National Cancer Institute, they are excellent at record keeping, all paper. And they dutifully pulled out some of the notes I wrote on my patients with Kaposi sarcoma with the references and citations. So this sort of nerdiness that we had at UCSF did transport to Kampala Uganda. DAVE JOHNSON: I hope they gave you some copies of those, with the name struck out of course, for your private collection. That's cool. SUSAN DESMOND-HELLMANN: It was actually pretty astounding to return. And now Fred Hutch has a collaboration with Uganda Cancer Institute and has done a lot of renovations and new science on the virology of Kaposi sarcoma. PAT LOEHRER: So before we skip from this and move to something else, if you could reflect a little bit about what you currently think the importance of global oncology is. It obviously had an influence on you. And how do you think it should fit in or does fit in now? UCSF has got its fingerprints around the globe now. I'm on their EAB. SUSAN DESMOND-HELLMANN: Well, let me just say from-- I'll speak to this sort of personally and then in a more big-picture way. Personally, I felt that the slogan of the Gates Foundation and every place can be too "slogan-y," so you always have to be careful about this. But the slogan that I just so had an affinity for is "all lives have equal value." All lives have equal value, for me, says that someone struggling or suffering, no matter where they are in the world, is worthy of our care and attention. And global oncology, I think, reflects that. So one of the things that I learned when I was there-- and I felt really good about this. I was glad that I learned from colleagues in Uganda and they learned from me. And so there was a real collaboration on figuring out-- I'll give you a real example. As you know, Kaposi sarcoma causes a lot of edema and lymphedema in the lower extremities. Well, if you've got lymphedema in your lower extremities, you can't farm, you can't dig, you can't feed your family. And we had bleomycin and vincristine. And with a combination of those two, in relatively small amounts to avoid toxicity, I could get someone back on their feet literally. And well, that's a great thing. And so the practical nature of symptom improvement, the avoidance of side effects, the attention to quality of life was amplified by my experience there. So I think those kinds of things-- I always like, in life, you give and you get. I gave. I contributed. I worked hard. And I got a lot of new knowledge and understanding. In addition, the deep understanding of pathophysiology that came from thinking about African Kaposi sarcoma, Mediterranean Kaposi sarcoma, age-related Kaposi sarcoma. There's just a lot of science, just a lot to learn if you were paying attention and probing what was going on. So I think global oncology is extremely important. And it's important that it be sustainable and appropriate and with, always, service and training as a component, not only research. PAT LOEHRER: Agreed. I agree. DAVE JOHNSON: We have so much to cover, I don't want to spoil everything. But I'm really curious when you left Uganda, you went into private practice, right? SUSAN DESMOND-HELLMANN: Mm-hmm. DAVE JOHNSON: How did that happen? SUSAN DESMOND-HELLMANN: We had to pay the rent. DAVE JOHNSON: There you go. SUSAN DESMOND-HELLMANN: Yeah. Yeah, when we came back, there was no global health. There was no place for us at UCSF. So we had one of those surreal academic experiences of sitting down with the new chief of medicine and him saying, there's no money for you. So you'll need to do a lot more clinical care and earn your salary. And Nick, you're going to-- my husband-- you'll need to write at least two R01 grants. And so you better get moving. And we were disappointed that there really wasn't a place or mentorship or anything for us at UCSF. But we didn't have time to lick our wounds. So Nick is from Kentucky. And we moved back to Lexington, Kentucky and went into private practice. DAVE JOHNSON: Yeah, economic necessity has changed. SUSAN DESMOND-HELLMANN: I mean, I can make it a little more romantic and interesting, but it was economic necessity. And honestly, I love patients, I love oncology, and I thought that was fine. One of the learnings from that was how deeply I missed research and R&D. And I'm very academically oriented. And so both Nick and I realized, when we were there, that we did very well. People liked seeing us as clinicians. And we were well-trained and could take good care of people. But it wasn't the right fit. DAVE JOHNSON: So from there, if I remember correctly, you transition to industry. SUSAN DESMOND-HELLMANN: Yeah, actually it's a good story. So Nick got called up about from Bristol Myers Squibb, did he want to come and join their infectious disease group up in Connecticut at Wallingford. And he said, of course, I would love that. But I won't come unless you take my wife too. And they said, no, we have a nepotism rule. We won't take your wife. And he said, well, you haven't met her yet. They said, why do we want a private practice oncologist at Bristol Myers Squibb. We need serious clinical trials people. And so Nick was somewhat persistent. And he just said, I won't come. He's a good husband. That's it. PAT LOEHRER: Sounds like it. SUSAN DESMOND-HELLMANN: He still is. And so they hired me as a consultant. And they were really busy on Taxol. It had gotten approved for ovarian cancer but not yet for breast cancer. And so I like to say they stuck me doing drug safety. And saying, she's like an LMD, she's a clinician. We'll have her do drug safety. She can't cause too much harm over there. And I tell you, the opposite of going into private practice, which was just, like I said, not a great fit. I felt like I had died and gone to heaven. First of all, it is probably embarrassing and says something about me, I loved drug safety-- loved, loved, loved drugs-- it's like thinking like an epidemiologist, a clinician, a good physician. You know, I love statistics and epi. I had gotten an MPH at Berkeley while I was an oncology fellow. And I just love analytics and inference and all of that stuff. And so after a couple of months they had changed me-- they got a dispensation from the CEO so I could be a real employee. And I became the project team leader for Taxol, which was fantastic. It was such a great experience. I loved the colleagues at BMS. And we were making one of the first new oncology drugs in a while. DAVE JOHNSON: Yeah, I think, if memory serves me correctly, that's about the time we first met. SUSAN DESMOND-HELLMANN: Yes. DAVE JOHNSON: And paclitaxel was being investigated in lung cancer. And that really is our connection. But those were heady times. We thought we were on top of the world. SUSAN DESMOND-HELLMANN: Well, you know, it had been a while since there had been new active chemotherapies in oncology. And they were heady times. It was also just so interesting and hard to remember now how much the toxicity of paclitaxel had put it on the shelf, this hypersensitivity reactions and the collaboration with the National Cancer Institute. There was a lot about the product development of paclitaxel that I remember and learn from. And I was just really grateful to be with Renzo Canetta and people like that, who it felt like going to UCSF where I thought, OK, Floyd Rector in nephrology. Now I get all these folks who I was using bleomycin and platinums. And they had written those package inserts. DAVE JOHNSON: Yeah. PAT LOEHRER: Yeah Bristol Myers basically owned oncology. I mean, all the products were going on there. And at that time, as you guys know, there's only one or two drugs a year that got approved for oncology. And today it is vastly different where each week there's a new drug or a new indication for oncology. The world has just changed tremendously. SUSAN DESMOND-HELLMANN: Yes. PAT LOEHRER: Yeah, it's been incredible. So Dave, where do you want to go next on this one? DAVE JOHNSON: Well, I think one of the things that I think our listeners might want to learn about is Sue's transition to Genentech. I mean, it wasn't like the powerhouse organization it is today when you went there. I mean, not that it was a hole in the wall, but it wasn't the biomedical powerhouse that it is. What attracted you? I'd love to hear from you, what brought you to Genentech? SUSAN DESMOND-HELLMANN: So I would say three things. The first thing was Art and his ambition. And so Art-- DAVE JOHNSON: You might want to tell people who Art is. SUSAN DESMOND-HELLMANN: So Art Levinson, who then was the head of R&D and later became the CEO of Genentech, so Art Levinson worked in Mike Bishop's lab at UCSF. And so he, in many ways, showed up as a molecular oncologist as the head of R&D at Genentech. And his ambition was that Genentech would be an oncology company. When I talked to Genentech, they had precisely zero oncology drugs. The furthest along was gamma interferon in their pipeline. So it didn't actually look very promising at the time. But Art was very compelling to talk to, and his dream. The second thing was research. Bristol Myers Squibb was fantastic. But especially being in Connecticut, where you were sort of removed from the research enterprise, I saw BMS as fantastic clinical development organization and sales organization. They did a lot of licensing deals. That was their claim to fame was they were really good at licensing. And I respected that a lot. But the ability to sit down with the research folks and think about what you would do with an anti-HER2 or an anti-VEGF-- and I just really respected Genetech's research capabilities and organization. And the third thing was we made the decision-- which wasn't an easy decision to make. We had built a house in Connecticut. We were happy there. I don't know if you remember the winter of '94 was huge blizzards in Connecticut. Before we moved to Connecticut, I didn't even own a winter coat. So it was rough to experience winter in the Northeast. And my family was in Reno and San Francisco. And so moving back here was compelling. PAT LOEHRER: Not the romance that you had in Christmas in Connecticut with Bing Crosby. It just wasn't the same, was it? SUSAN DESMOND-HELLMANN: Well, I did love fall. I'll tell you, nothing like autumn in Connecticut. There's a lot to like about Connecticut. So it wasn't an easy move. But coming back West was a good thing. DAVE JOHNSON: Well, what was the first really successful product that you worked on with Genentech? I should know, but I don't remember. SUSAN DESMOND-HELLMANN: Oh, the first successful product that I worked on with Genentech was a collaboration with IDEC on Rituxan. And rituximab was really interesting because there's some real heroes at Genentech, including a business development guy, David Ebersman, who heard that maybe an antibody could work, even a chimeric antibody could work for lymphoma. And so with Antonio Grillo-Lopez and the rest of the folks at IDEC, we got the first antibody approved in 1997. And that made a massive difference. I don't think people recognize how important rituximab was for trastuzumab, which was really only a year later-- less than a year later-- approved for HER2 positive breast cancer. But for me, that opened the era of antibodies and made people believe you could repetitively give a patient with cancer an antibody and they would tolerate it. DAVE JOHNSON: How confident are you that would work? SUSAN DESMOND-HELLMANN: I was very confident that rituximab would work. There was a lot of information. I wasn't sure we could make it. That required a lot of biotech manufacturing expertise that Genentech had, which was great. But I felt good about that. But there was a myth, at the time, that you could treat a liquid tumor, you could do heme, lymphoma or leukemia with an antibody. But there was this big worry you couldn't get into the tumor with a solid tumor. So I was not at all confident about Herceptin. Trastuzumab was not a give-me. But rituximab I was confident about. PAT LOEHRER: This concludes part one 2-part interview with Dr. Susan Desmond-Hellmann. It was a wonderful discussion. In part 2, we'll talk a little bit more about Dr. Desmond-Hellmann's incredible leadership roles, including her time as chancellor at UCSF and the CEO of the Bill and Melinda Gates Foundation. Thank you to all our listeners for tuning into Oncology, Etc. an ASCO Education Podcast where we'll talk about anything and everything. If you have an idea for a topic or a guest you'd like to see on the show, please email us at [email protected] Thanks again. And just remember anything, because Dave doesn't. SPEAKER: Thank you for listening to this week's episode. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.
  • ASCO Education Podcast podcast

    Social Determinants of Health - Access to Care

    20:15

    In this Social Determinants of Health (SDOH) episode, Dr. Deepak Vadehra (Roswell Park) moderates a discussion with Dr. Carmen Guerra (Abramson) and Dr. Daniel Carrizosa (Levine) on how access to care impacts SDOH and the available interventions and resources that can mitigate these issues for patients. View COI & Cancer.Net Podcast. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 10/28/2021 TRANSCRIPT [MUSIC PLAYING] LORI PIERCE: Hello. I'm Dr. Lori Pierce, the 2020-2021 President of the American Society of Clinical Oncology. Thank you for tuning in for this discussion on social determinants of health and their impact on cancer care. The purpose of this video is to educate and inform. It is not a substitute for medical care and is not intended for use in the diagnosis or treatments of individual conditions. Guests on this video express their own opinions, experiences, and conclusions. These discussions should not be construed as an ASCO position or endorsement. For this series on the social determinants of health, we invite guests with a wide range of views and perspectives. Some of these conversations may be provocative and some even uncomfortable, but ASCO is committed to advancing equitable cancer care for all individuals, every patient, every day, everywhere. I dedicated this vision to my term as ASCO president, and these conversations bring many voices to the table, voices that we need to hear to move forward and find solutions. We hope you learn new ways of thinking about these issues, and we invite you to join us in working toward a world in which every person with cancer, no matter where they live or what resources they have, receives high-quality, equitable cancer care. Thank you. DEEPAK VADEHRA: Welcome to the 10th episode of the ASCO Social Determinants of Health Series. I am Dr. Deepak Vadhera, and I'm a GI medical oncologist at the Roswell Park Comprehensive Cancer Center. I am joined today by Dr. Carmen Guerra, who is Associate Director of Diversity and Outreach at the Abramson Cancer Center at the University of Pennsylvania, and by Dr. Daniel Carrizosa, Medical Director of the Disparities and Diversity Program at Levine Cancer Institute in Charlotte, North Carolina. In this episode, we will be discussing access to care and how it impacts the social determinants of health and the available interventions and resources that clinicians can utilize to mitigate these access issues for their patients. So thank you very much to both Dr. Guerra and Dr. Carrizosa for being here. When I, sort of, think about access to care, I intimately equate it with equity. I think that, at its core, access to care is an equity issue and that not every solution is appropriate for every patient. But I think that the important thing is that, as we move forward in our discussion and sort of as we think about things globally, that we all recognize the importance of allowing appropriate access to care and making sure it is equitable for all our patients. So with that in mind, Dr. Guerra, one of the things that I think about in access to care are barriers, and one of the biggest areas, I think, is that we need to improve, with terms of access to care, is the access to clinical trials and the coverage of clinical trials. So I know that's something you're passionate about and so would love to hear some of your thoughts on that and other barriers you see, in terms of access to care. CARMEN GUERRA: Thank you, Deepak. First of all, it's a pleasure to be here. Thank you for the invitation. And yes, I'm very passionate about the equitable access to cancer treatment trials, and it's a space that I've been working on. We know there are inequities in accessing trials, because we know that the proportion of Black individuals that participate in trials is very small. In the 28 new oncology drugs approved by the FDA between 2018 and '19, If you look at all the participants, only 4% were Black. And we saw this, as well, in our own Abramson Cancer Center. In 2014, we just presented data at the ASCO National meeting, where we saw that even though in our catchment area, the proportion of Black patients with cancer was about 16.5% in our catchment area, the patients who were coming to the Abramson Cancer Center who were Black was only 11.1%. So I call that a community-to-clinic gap. And then we looked at who was participating on trials, and that was about 12.2% of the population was Black. And so we began, in that year, 2014, on a whole series of strategies to understand, better understand and address the barriers. And one of the barriers that we focused on was transportation. Nationally, we know that Black individuals are less likely to have a car, own a vehicle. About 20% of Black households do not have access to a vehicle. So one of the things we developed was a transportation program. We also worked on building partnerships with faith-based groups that serve the Black communities, as well as nonfaith-based groups, to increase our ability to go out to the community and educate the community about cancer, cancer prevention, and clinical trials. And then in addition, we also did some internal things. We worked with our PIs to show them-- our investigators-- to show them where the burden of cancer in the Black communities was. What were the cancers, and what were the trials we needed to design for them? And then we also asked them to include a minority participation paragraph in all protocols they submitted. And so in 2018, we were able to reassess the data. And what we found was a two-fold increase in the individuals who are coming to the Abramson Cancer Center because now, they had access through transportation and information. And then we also saw a two-fold increase in the individuals who participate in on clinical trials. And for us, that really showed us that we could do this, that we could provide the equitable access to cancer clinical trials. And so that just has continued to embolden us to continue to work on this, because I think you do have to sustain your efforts. Otherwise, we might see the same statistics that we saw back in 2014. DEEPAK VADEHRA: No, I couldn't agree with you more. And those are great interventions and great ideas that the Abramson Cancer Center was able to roll out. Dr. Carrizosa, what do you see as some of the barriers to our patients being able to access the care that they deserve as cancer patients? DANIEL CARRIZOSA: Yes, I think it's very interesting, because I think there's a lot of questions you can ask, in general, that help you think about these barriers to care. And Dr. Guerra was just talking about, almost, the what. You know, what do we do for patients so that we can get things done and help them? So other things are, simply, the question of who is it that you're looking at? What different type of person it is-- is this a elderly person that we need to think of different options, like different trials, different therapies? Do we also have to look at how they can access information? Is telemedicine something that's very easy for them? Or are they not able to use a smartphone? You also have to think about people with differences, such as transgender patients, who sometimes have significant, unique interactions with the medical community and unique needs, and we need to think about them. Also, at our annual Think Academy, which is a large conference we do that looks at inequities, we had Susan Magasi, from the University of Illinois Chicago, come and speak. And she really opened my eyes, because she talked about disabled people. And I had never thought about how a disabled person gets a mammogram. So that's a who and a how. On top of that, we also think about where. So we've talked a little bit about the transportation issue, and we have transportation issues in cities, rural, how they get telemedicine or broadband, where they might actually have a medical center close to them. They could be in parts of the country where people have to drive hours to be able to get good cancer care. And then the why. What is it that we're trying to do for them? And importantly, how can we educate people about cancer and about what these barriers are and how we can try it overcome them. DEEPAK VADEHRA: I think those are all very important points that you make, and things that we are all very important to think about as we move forward in both designing trials and working on improving our access for our patients. I think one of the things that providers and practitioners, who may not be in urban centers or are community providers and not, quote, unquote, academic providers, like we are-- what resources, what practical things can they do to help, sort of, break down the barriers and break down the walls that prevent patients from getting the proper access to appropriate clinical trials and supportive care, such as that? So Dr. Guerra, have you-- what are some practical tools out there that providers can use to help lessen the burden of access to care issues? CARMEN GUERRA: It's an important question, and thank you, so much. One of my volunteer hats is that I am the Board Scientific Officer for the American Cancer Society. And they have programs precisely to help individuals with access issues, such as transportation, such as lodging. One of their programs is the American Cancer Society Road to Recovery Program. And this is a program that provides transportation to patients with cancer to their appointments. It was a program initially launched back in the 1960s, but it was adopted nationwide by the American Cancer Society in 1983. And it's available to anyone with a diagnosis of cancer. They have provided, in the past, before the pandemic, in a year, about 35,000 patients were served with almost half a million rides, and it's available, again, for free, if you go on their website, cancer.org. And there's a phone number, which I'll be happy to share with your listeners. It's 800-227-2345. And that's a general American Cancer Society number for any services that they provide. The second resource from the American Cancer Society is the Hope Lodges. The Hope Lodges are a system of 30, maybe 31 now, lodges all across the United States and Puerto Rico that provides, again, free-of-charge accommodations to any patient with cancer. Now, the eligibility requirements vary by location, especially during this time of COVID. But again, that same number or cancer.org a way to identify those resources for patients who need access to care or access to clinical trials. DEEPAK VADEHRA: Great. That's very important. And I hope that everyone who's listening can recognize and be able to use those tools at their disposal. Dr. Carrizosa, what do you think are some other ideas and resources? What has worked in your experience? And is there something, maybe out of the box we need to do? And sort of, let me-- tell our listeners, sort of, about your experience. DANIEL CARRIZOSA: Sure, I think, bouncing off what we just talked about, organizations in the community, like ASCO, are incredibly important to use and to form trust with the community, as has been described in some of these podcasts before. But more importantly, sometimes with these access issues, we actually need to think of new and different ways of trying to engage and bring people into cancer care or screening. And one of the things we do here at Levine Cancer Institute, is we created the first mobile lung cancer screening unit in the country. And we saw a large number of patients with transportation issues in the rural communities that were a little bit wary of coming to, either, a brick and mortar screening area or a cancer center, and we wanted to overcome that. So we actually made this mobile unit. We actually come into the community. We do community assessments to build that trust. And we do multiple screenings, other than just lung cancer screening. We also do head and neck screening. We're starting prostate screening through blood work. Controversial, but it was something we're looking at. And on top of that, we're also basing research studies in the community on our, what we call, Lung Bus Initiative. And so thinking outside of the box and trying to find other ways in your community that you can look. Can you do mobile units inside an urban community? Can you then provide other options? Do we do navigation? We're very big at navigation here Levine Cancer Institute. We have a Spanish-speaking navigator just for those patients. It actually overcomes communication issues. Trying to call in to the actual Cancer Center and again, comes back to building trust. So I think it's important to, A, take your community boards and your focus groups, all of these areas-- talk with them. Find out what is important in your community, and what are those barriers? What are those obstacles? And then sit down and think about what can we do? And sometimes, aim for the stars. DEEPAK VADEHRA: No, I think that, that is definitely a great example of out-of-the-box thinking and being able to take something that's vitally important to the community. And it definitely can have a great impact on our patients being able to access the things they need, and that's not just once cancer is diagnosed. That's before the diagnosis is made and for screening. So that's a really, really wonderful example that you gave there. So we've talked a little bit about the barriers, what we see as issues, and some practical resources that providers can use to help. But at the crux of the issue, really, is policy, and what we need to do at that policy level to try and really impact and improve the availability of care for our patients. So I'll start with Dr. Carrizosa. Dr. Carrizosa, what are some of the policy issues that you see as being central to improving access to care for our cancer patients? DANIEL CARRIZOSA: Well I think, ultimately, when people start thinking about policy, they start getting very worried. And how am I going to change things? I'm just one person. And so, one person can move a mountain with the right, you know, ability or leverage. And so I think you start at your local community, and we can look at things like transportation. What type of transportation is available, or where can people go and get things they need? I think in the last podcast, they discussed food islands and food deserts. And so therefore, can you use something where you're actually overcoming that, and then increase awareness for cancer screening or trials? On top of that, then you have to go to state levels, and then you start talking about, well, can you increase broadband? Can you do other things that can actually help? Can you just make there more education happening? And then, obviously, the national level, people get very worried, and they try to figure out, well, how am I going to change national policy? And one great way is actually through ASCO advocacy. And so they actually are working through different telehealth modernization acts and going every year to speak with our representatives to try and change and make things better for our patients. So I don't think, you know, you need to feel like you need to become president to change these things. You can do it in your community, you could do it at your state, or you can use an organization, like ASCO, that's actually changing policy or helping to change policy. DEEPAK VADEHRA: Now, those are all great points. Dr. Guerra, your thoughts about what you feel like the important policy issues that we have to tackle in order to help improve access to care. CARMEN GUERRA: Yeah, I mean the big one is, of course, the insurance, access to insurance. And we've-- I agree, ASCO and the American Cancer Society, have lobbied for expansion of insurance, first through the Affordable Care Act but now through Medicaid expansions through the state. And I think that, that is absolutely vital for, not just cancer care, but all types of health care for our patients. I would say, there's a second policy that was just recently approved and that is an opportunity for the clinical trial space. And that's a policy that will now mandate Medicaid, starting in January of 2022, to cover the routine costs associated with clinical trial participation. And in so doing, Medicaid will join private insurers and Medicare, which already do cover those clinical trial-related costs. And so I think with that, we'll have an opportunity, as well, to expand access to the potential treatments of the future to patients who want to participate in trials. And then the last one I'll mention is that we have been working with a foundation, called the Lazarus Foundation. And what they do is they reimburse patients for the travel-related costs, as I mentioned earlier, and that includes lodging and travel. But in order for us to be able to do that, we first had to lobby our state Senate to actually create a law that says that reimbursing individuals for those clinical trial participation costs is not undue influence. It's not coercion. And that bill passed unanimously, and similar bills have passed in states like California and Texas and Illinois and Wisconsin, and I think, most recently, Massachusetts, in January of this year. But doing this state-by-state is not very efficient. And so what we also need is a federal policy with that type of language that allows, potentially, pharma and other sponsors to reimburse our patients for those travel-related costs associated with clinical trial participation. DEEPAK VADEHRA: No, I think that's absolutely paramount to being able to provide the best care to patients. You know, I think, sometimes, that we forget that clinical trial doesn't mean everything is picked up, cost-wise, in a clinical trial. And there is definitely a standard of care part that somebody has to pay for, right? And I think that is one of the most important things. And I think it's great that we are able to bring awareness and have a sense of what we can do to help advocate for policy changes. And I think that was a great discussion. I know we could talk about this forever. All three of us are very passionate about this. We're open to doing more sessions about it, but overall, thank you, Dr. Guerra and Dr. Carrizosa for joining us. I wanted to just mention that as a compliment to this episode, listeners may also be interested in a podcast from cancer.net with Dr. Karen Winklefield. She provides a brief introduction about social determinants of health and the resources available for patients and their families and other tips about finding resources that are available to help navigate the challenges of traversing the cancer care system. So a link to that podcast will be found in the description of this episode. And so once again, thank you, very much for joining us for this 10th episode of the ASCO Social Determinants of Health Series. To keep up with the latest episodes, please click "subscribe" and let us know what you think about the series by either leaving a review or by emailing us at [email protected] Thanks, everyone, for their time today. CARMEN GUERRA: Thank you. DANIEL CARRIZOSA: Thank you. LORI PIERCE: Thank you for listening to this week's episode of the ASCO eLearning weekly podcasts. To make us part of your weekly routine, click "subscribe." Let us know what you think by leaving a review. For more information, visit the Comprehensive eLearning Center at elearning.asco.org.
  • ASCO Education Podcast podcast

    Cancer Topics - New Therapies for Lymphoma (Part 1)

    26:53

    In part one of this two-part ASCO Education Podcast episode, Dr. Sonali Smith (University of Chicago Medicine) and Dr. Paolo Strati (MD Anderson Cancer Center) discuss the application of recently approved therapies for diffuse large B-cell lymphoma through examination of challenging patient cases. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 10/20/21   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] SONALI SMITH: Hello, and welcome to this episode of the ASCO Education Podcast highlighting new therapies for lymphoma. My name is Dr. Sonali Smith, and I'm a hematologist and medical oncologist specializing in lymphoma and clinical investigation in lymphoma. I'm also the Elwood V. Jensen Professor and chief of the hematology/oncology section at the University of Chicago, and very excited to be joined by my colleague, Dr. Paolo Strati. PAOLO STRATI: Good morning to everybody. My name is Paolo Strati. I'm a hematologist and medical oncologist and an assistant professor in the Department of Lymphoma/Myeloma, and in the Department of Translational Molecular Pathology at MD Anderson Cancer Center, Houston, Texas. And I'm also the clinical director for the Lymphma Tissue Bank. In part one of this podcast episode, we will discuss the adoption of recently approved therapies for diffuse large B-cell lymphoma, such as selinexor, tafasitamab, Liso-Cel, and Lonca-T. These therapies have transformed care for patients with this disease. And we'll start our conversation today with a patient case. SONALI SMITH: Great. Well, I'll go ahead and present a patient to you, Paulo. So this is a 78-year-old man with diffuse large B-cell lymphoma that is the germinal center-derived subtype. It is not double expressor, it is not double-hit. He has advanced stage disease with a high IPI, as well as the high CNS IPI. Luckily, his performance status is zero and he has no significant comorbidities or other health conditions. He received frontline dose-adjusted EPOC-R with intrathecal methotrexate for six cycles. But at the end, he had a partial remission. So how do you select your salvage therapy in this situation? Are you concerned about using agents targeting CD19 in the second line, given the potential need to use anti-CD19 cellular therapy, or CAR-T in the third line? PAOLO STRATI: This is a very interesting and unfortunately not uncommon case. And thank you, Sonali, for asking these very important questions. Technically, a platinum-based regimen followed by autologous transplant will be a standard answer and may be feasible. Because as you mentioned, this patient has a good performance status and non-meaningful comorbid health conditions. However, patients who are refractory to a frontline anthracycline-based regimen, such as in this case, with achievement only of partial remission at the end of frontline dose-adjusted EPOC, can potentially experience a suboptimal outcome following the standard approach with a platinum-based second line regimen. And as such, alternative strategies may be needed. To this regard, the combination of tafasitamab that, as you know, is a monoclonal antibody targeting CD19, and lenalidomide, an oral immunomodulatory agent, a combination which is currently approved by the FDA in the United States as a standard second line option for transplant ineligible patients, would be a great option in this case. Data from the three year follow-up of the phase II study that has brought to the FDA approval this combination, the L-MIND had been recently presented and have showed the complete remission rate of 40% and immediate duration of response of 44 months, including patients who received this regimen as a third line or beyond. So there is, of course, a biological concern by targeting CD19 in second line. These may potentially impact a third line use of an autologous anti-CD19 CAR-T, because CD19 downregulation may potentially be a mechanism of escape to tafasitamab. And recent data has shown the CD19 levels are strongly associated with the efficacy of CAR-T cell therapy in patients with large B-cell lymphoma. Small retrospective studies have shown that autologous anti-CD19 CAR-T can be safely and effectively used after antibodies or antibody drug conjugate targeting CD19. But we need a significantly larger and prospective data, including serial tissue biopsy in these patients before considering this combination as a standard practice in patients for whom we plan to use CAR-T as a third line. Until then, I would be cautious in using second line tafasitamab in patients, again, for whom there is a potential plan for anti-CD19 autologous CAR-T in third line. And if necessary, limited to very selective cases. Finally, recent press releases have anticipated the two autologous anti-CD19 CAR-T products, Axi-Cel and Liso-Cel, are superior to autologous settings transplanted in second line. And so in the near future, CAR-T cell therapy may become a standard second line option. And that would be an ideal option in primary chemorefractory patients as the case that you presented here. SONALI SMITH: Yeah, I agree. There are a tremendous number of options. And having anti-CD19 products as well as autologous stem cell transplant, the sequencing will be an evolution. So going back to this patient, he received tafasitamab and lenalidomide for two cycles with no significant toxicity, but unfortunately, he had further progression after two cycles based on a PET/CT scan. So what are your next steps? Would you move directly to an autologous anti-CD19 CAR-T cell therapy now? Would you re-biopsy before that? And how would you select among the three available CAR-T products? PAOLO STRATI: These are not easy questions, particularly the selection of one out of three available CAR-T products. As you said, there are currently three autologous anti-CD19 CAR-T products approved by the FDA in the United States for the treatment of large B-cell lymphoma in third line or beyond. And these are Axi-Cel, Tisa-Cel, and Liso-Cel. For all of them, the best outcome is observed for patients who have a low turmor burden at time of CAR-T infusion. And they need to either select patients with no bulky disease or to decrease it through bridging therapy. And as we define bridging therapy given between leukapharesis and CAR-T infusion. Unfortunately, there is currently no standard bridging therapy and all FDA products approved in third line can potentially be used in this specific scenario that you described, including polatuzumab with bendamustine/rituximab, selinexor, and Lonca-T, of course, beyond tafasitamab and len that has already been used in this case. Of course, when selecting a bridging therapy, there are many disease-related and patient-related factors to take into consideration, including the need to preserve the host immune microenvironment that we all know is crucial for the subsequent activity of CAR-T cells. And also, we need to give into consideration the need to preserve as much as possible, as we discussed previously, in CD19 expression. To this regard, and going back to one of your questions, I strongly recommend to re-biopsy patients if any bridging therapy is used between bridging therapy and CAR-T infusion in order to document CD19 expression before CAR-T infusion. When it comes to CAR-T product selection, as I said, it's a really difficult decision to do. And we don't have at this time randomized trials in third line. And as such, the decision is really left to the treating physician based on multiple factors. But all of the limitations of inter-study comparison, efficacy seems to be pretty much the same for the two products, maybe slightly higher based on the recent second line data. But Axi-Cel and Liso-Cel as compared to Tisa-Cel, and also as suggested by recent press release. However, due to the fact that Liso-Cel and Tisa-Cel have less potent co-stimulatory domain for 1BB instead of CD28, the rate of CRS and ICANS, the two main toxicities associated with CAR-T cell therapy, is usually lower with this to the point that some centers are able to infuse them in the outpatient setting, whereas Axi-Cel is almost always infused in the inpatient setting so the toxicity can be monitored more closely. So with older patients or those who have comorbid health condition, Tisa-Cel and Liso-Cel may be a safer option, though there's a lot of research going on trying to mitigate toxicities associated with Axi-Cel. Finally, it's important to keep in mind manufacturing time. Axi-Cel is manufactured in an average of 17 days, whereas Tisa-Cel and Liso-Cel take typically longer than three to four weeks. This can be itself a determining factor, particularly for patients who are quickly progressing and where immediate treatment is needed. SONALI SMITH: Yeah, I agree. I think there are going to be many patient product and disease-based factors that will impact both the effectiveness as well as the toxicity. And you did a really great job of explaining the role of the co-stimulatory domain potentially in some of that, as well as all of the products that are out there. It's definitely a complicated area. Going back to our patient, so he did undergo leukapharesis for Liso-Cel and received third line polatuzumab and rituximab without bendamustine. The restaging PET/CT after two cycles showed a PR with a significant decrease in tumor burden, and repeated biopsy showed high expression of CD19 by flow cytometry. He then proceeded with Liso-Cel, which was relatively well tolerated. There was only grade 1 cytokine release syndrome and no ICANS, so no neurotoxicity. And his day 30 PET/CT showed a complete remission. Unfortunately, the 90 day PET/CT showed progression. So Dr. Strati what is the outcome for patients who relapse after CAR-T? Do you recommend to re-biopsy? And what are the efficacy data for FDA approved agents for these patients? And I know this is a long question, but is there any role for repeated CAR-T or allogeneic transplant now? PAOLO STRATI: Unfortunately, currently, the outcome of patients with large B-cell lymphoma relapse or progress after autologous anti-CD19 CAR-T is suboptimal, with a life expectancy, unfortunately, shorter than six months. Hence, the need to be creative and customize treatment based on biological data. To this regard, I think it's crucial to repeat a tissue biopsy to guide subsequent therapy. As mentioned previously, there are currently four products approved by the FDA for patients with large B-cell lymphoma in third line and beyond. Two of these target CD19, tafasitamab plus lenalidomide and Lonca-T One targets CD79B, polatuzumab combined with bendamustine and rituximab. And one is an SPO1 inhibitor, selinexor. While we have no data for selinexor in patients who relapse or progress after CAR-T cell therapy, limited prospective data showed that a progression-free survival in the order of weeks is usually observed for patients who receive polatuzumab with or without bendamustine and rituximab after CAR-T cell therapy. So I would not recommend that. However, there's some interesting activity in the post-CAR-T setting for Lonca-T and for tafasitamab/len is limited to patients who still express CD19 in time of relapse. And of course, it needs to be largely and prospectively further investigated before becoming a standard approach for patients who relapse or progress after CAR-T cell therapy. When it comes to cellular therapy, repeated anti-CD19 CAR-T infusion is not shown to be successful in the original registration studies. So it is not currently something that I would recommend and is not definitely a common practice. And very limited retrospective studies have shown the use of allogeneic stem cell transplants in the post-CAR-T setting may be associated with quite elevated treatment-related mortality. So I don't suggest this as a standard practice in large B-cell lymphoma at this time. This is different from B acute lymphoblastic leukemia, where instead, allogeneic stem cell transplant is becoming progressively a standard approach. And we definitely need more data before using this consistently. While we strive to identify the optimal cell batch therapy for large B-cell lymphoma patients who relapse or progress after CAR-T cell therapy. I think the priority should be given to clinical trials, including CAR-T targeting molecules other than CD19, such as CD20, CD22, CD79B, allogeneic CAR-T there are immediately available, so without the need to wait for manufacturing times. And K-CAR, that may be less toxic than CAR-T and other non-cellular therapy biological agents. So definitely, clinical trials are, at this time, the best approach in patients who relapse after CAR-T cell therapy, as the case that you described. SONALI SMITH: Thank you Dr. Strati. As an update, this patient had repeated biopsy showing a CD19 positive relapse. He consented for a clinical trial with a novel NK-CAR targeting CD19, achieving CR which is still ongoing at nine months. And this case really does represent some of the most exciting advances that we've had for this disease for patients who can tolerate aggressive therapies and have access to clinical trials. PAOLO STRATI: Dr. Smith, I'd like to hear your opinion about another patient with diffuse large B-cell lymphoma. This patient is an 81-year-old man with a history of coronary artery disease and well-controlled diabetes mellitus, who noticed a right cervical lymph node while shaving that seemed to have popped up. He was evaluated by his primary care physician and given a course of antimicrobials. 10 days later, the lymphoma seems to be enlarging and he is referred to ENT pharyngeal biopsy. The specimen is small but shows follicular lymphoma in a portion of the sample. However, there is also concern for larger cells and possible transformation. The patient is also beginning to note night sweats and a decreased appetite. And labs are notable for elevated LDH, 500, and thrombocytopenia with a platelet count of 110. So Dr. Smith, in your opinion, is this specimen sufficient to start treatment? Or should treatment be delayed to get a larger and maybe excisional biopsy? SONALI SMITH: Yeah, thank you for this question. I think this is a challenge we have in the clinic all the time, which is what is a sufficient biopsy specimen to make a diagnosis that allows us to subtype lymphoma? As we know, every lymphoma subtype, the treatment is really guided by the histology and not so much the stage or some other factors. So having a needle biopsy is unfortunately often insufficient. In this case, we have a very strong concern for a possible transformation. And as we know, both follicular lymphoma and diffuse large B-cell lymphoma can mark very similarly when it comes to immunophenotype. Certainly, the germinal center type of diffuse large B-cell lymphoma or any transformed follicular lymphoma will be CD20 positive, CD10 positive, and it really requires architecture to be able to tell whether or not there are sheets of large cells. So the ideal outcome for this patient would be to have a biopsy that is done promptly that allows us not only to confirm whether or not there is histologic evidence of transformation, but also to conduct FISH studies to determine if there's acquisition of a MYC rearrangement. At its core, all follicular lymphoma patients essentially have a transformation of 14;18, leading to BCL2 rearrangement and BCL2 overexpression. During the transformation process, there can be an acquisition of a MYC rearrangement, which would then make this a double-hit lymphoma and certainly has a much worse prognosis and may also prompt a change in treatment if the patient can tolerate more intensive therapy. So my recommendation would be to have a biopsy. Now one other aspect is that sometimes, we don't really have the time to proceed with a biopsy, or the lymph node may be in an inaccessible area. And in that case, there are some other criteria that we can use to assume that somebody has a transformation. Symptoms such as profound B symptoms and elevated LDH, and sometimes, a PET scan with multiple areas of very high avidity, can lead you to feel or suggest that this person has a transformation. There is some controversy over the use of PET and we know it does not confirm a diagnosis of transformation. But in my opinion, this is very suggestive if there are many areas of high SUV. PAOLO STRATI: Thank you, Dr. Smith. I agree completely about the importance, when time allows, to perform either a larger core biopsy or an excisional biopsy, because as you very well-outlined, this has not just a mere diagnostic purpose, but can meaningfully affect treatment planning for patients. And actually, in this case, as you suggested, the patient eventually had multiple core biopsy that showed transformed follicular lymphoma with very evident areas of diffuse large B-cell lymphoma. FISH, as expected for follicular lymphoma, was positive for translocation for TN18, but luckily negative for MYC rearrangement. So fortunately, we didn't have to deal with a double-hit lymphoma. The remainder of his staging showed he had diffuse lymphadenopathy. And PET scan, as you mentioned, has a controversial role in the diagnosis of transformation. So there's some areas that had high avidity with an uptake with an SUV of 1215, whereas other areas were less intense with SUV 618. And usually, heterogeneity in SUV actually helps further supporting diagnosis or transformation. While meta-maps showed follicular lymphoma, no large cells. So movement was isolated in the B-cell lymphoma. So Dr. Smith, at this point, based on the provided information, what's your treatment approach in this older patient and also a patient with comorbid health conditions, but with diffuse large B-cell lymphoma? SONALI SMITH: Yes. The goal of treating any aggressive lymphoma is to obtain remission, and if the remission lasts, to hopefully offer cure to the patient. And when somebody has a transformed lymphoma, of course, there is a dual concern, which is that the aggressive component can potentially be put into remission in a durable way achieving cure. But the indolent component will always need to be monitored, although hopefully, will not be life threatening the way the aggressive component can be. Treating an octogenarian is really challenging, particularly due to comorbidities in this age group and the potential toxicity of chemotherapy. So the standard of care for diffuse large B-cell lymphoma is anthracycline-based chemotherapy. But this, of course, can have significant toxicity in older patients. And in addition, the vincristine can aggravate neuropathy. And I've personally found that the high dose steroids that are part of CHOP can also cause toxicity in older patients and patients who are frail. So unfortunately, the literature is somewhat sparse. But we do have several data sets that can guide management in this particular patient situation. The French published, over a decade ago, the development of R mini CHOP, that includes an attenuated dose of cyclophosphamide, doxorubicin, and vincristine, and leads to some durable remissions and cure. Unfortunately, the long-term overall survival is less than 50% with R mini CHOP. And so although this is an appropriate backbone, there's certainly a lot of room for improvement. And there's also toxicity even with R mini CHOP. So in their initial phase II trial, there was actual deaths related to the R mini CHOP, particularly in the first cycle or two, really necessitating some type of pre-phase help ease patients into the chemotherapy. One of the challenges that we face in the clinic is that when we meet an older patient, we both want to maximize our chance for cure, but also minimize the toxicity that is particularly pronounced. And there is very little data in terms of how to guide this at the bedside. I'm excited that SWOG, with the US Intergroup, is conducting a trial, S1918, which prospectively includes a frailty assessment tool that was developed by the Italian group in lymphoma, and then also includes serial comprehensive geriatric assessment so that we can get a better idea about quality of life both during and after treatment. So there is no great standard of care right now, but I would say that R mini CHOP, outside of a trial, is a very reasonable way to proceed. PAOLO STRATI: Dr. Smith, thank you for outlining so well what we can do to minimize toxicity and to better select patients for this type of treatment. And as an Italian practitioner in the United States, I am very excited that the Italian frailty tool will be used in this SWOG trial. Are there any other ways to further improve safety when we use chemo immunotherapy in older patients or patients with comorbid health conditions? In particular, there is a lot of concern about potentially infectious complications in these patients. And so I'm wondering if there's any routine antimicrobial prophylaxis that you recommend. SONALI SMITH: Yes. I think it's really important to maximize supportive care for our older patients with aggressive lymphomas getting intensive therapy. I did mention the pre-phase, and I would just like to mention that one more time because I do think there's data that providing a brief pre-phase can minimize toxicity with the first cycle. And how this pre-phase is given is highly variable. Again, the data is somewhat limited, but it typically includes steroids given for five to seven days with or without a dose of vincristine. And steroids themselves can have toxicity. And the dose of the steroids, I think, is somewhat controversial. In my personal practice, I use somewhere between 40 to 60 milligrams per day for five to seven days. And I do not typically use vincristine, although a prospective French trial recently did and showed that this significantly improved toxicity. Other complications that can occur really are related to infection. And so, of course, all patients should have growth factor support as per ASCO guidelines. But I also routinely give VZV prophylaxis with acyclovir or valacyclovir. And for the first cycle in particular, I have patients come back to clinic after the first dose one week later to ensure that the counts are stable and that they are doing well. This is really where our team of nurses and other providers who are part of the care team are so important and communication is also very important. PAOLO STRATI: So Dr. Smith, as you suggested, also, this patient actually received mini R-CHOP without any complications. And end-of-treatment PET/CT can showed a VL score of 3, so a complete metabolic remission, potentially. How do you interpret these findings? SONALI SMITH: So response criteria in clinical trials, and then of course, extrapolated to the clinic, have evolved in lymphoma. And the Deauville or the International Prognostic Scoring System that has been used typically defines a uptake relative to liver and mediastinal blood pool. And those patients who have a Deauville 1 to 2, which is less than that bar, is considered negative. And 4 to 5 is positive, with five being the emergence of new sites of adenopathy. The interpretation of a Deauville 3 can be somewhat more complicated, but this really outlines the limitations of just using the SUV or the PET scan uptake to measure response. For my patient and for this patient, the lymph nodes all substantially decreased in size. And having some type of combined interpretation of the uptake, as well as the size that has decreased, I think is going to be a very important part of how we approach patients going forward. So for this patient, I opted for close observation after the completion of therapy and felt that his Deauville 3, along with the decrease in the size of the lymph nodes, was very significant. PAOLO STRATI: I completely agree with that. Where PET scan is an extremely helpful tool, particularly for the management of aggressive B-cell lymphoma, can also become a major challenge when it comes to its interpretation for these borderline scenarios. And as you said, it's very important to add into the equation multiple parameters, including CT findings and overall patient performance status symptoms. So that's all we have for today. Thank you, Dr. Smith. This was a great conversation. We have learned and discussed a lot about diffuse large B-cell lymphoma, including novel biological agents, CAR-T cell therapy, management of elderly patients, and patients with comorbid health conditions and interpretation of PET/CT scan. I think this will be very helpful. And the conversation will continue beyond this podcast. In part 2 of this episode, airing in November, we will discuss new therapies for mantle cell lymphoma and for follicular lymphoma. Thank you so much to all the listeners tuning into this episode of the ASCO Educational Podcast. SONALI SMITH: Thank you. It's been a pleasure to speak with you today. [MUSIC PLAYING] SPEAKER: Thank you for listening to this week's episode of the ASCO e-learning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.
  • ASCO Education Podcast podcast

    Oncology, Etc. - In Conversation with Dr. Otis Brawley (Part 2)

    19:40

    In the second edition of this two-part Oncology, Etc. episode, hosts Dr. Patrick Loehrer (Indiana University) and Dr. David Johnson (University of Texas) continue their conversation with Dr. Otis Brawley, a distinguished professor of Oncology at Johns Hopkins and former Executive Vice President of the American Cancer Society. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: elearning.asco.org | Contact Us Air Date: 10/5/2021   TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] DAVID JOHNSON: Welcome back to Oncology, Etc, and our second segment of our conversation with Otis Brawley, professor of Medicine at Johns Hopkins Medical School and the Bloomberg School of Public Health. Pat, I don't know about you, but Otis is a very impressive man, and he had a lot of really interesting things to say about his career development, family, et cetera in the first segment. This second segment, we're going to get to hear more about his time at the ACS. What were your thoughts about segment one? PATRICK LOEHRER: Well, I loved talking to Otis, and you too, Dave. Parenthetically, Otis once told me in a dinner conversation we had that he felt like Forrest Gump, and I can identify with that. Where over the field, our field of oncology over the last several decades, we've met some incredibly wonderful people, and we've been lucky to be part of the history. The three of us, I think, do have a deep sense of the historical context of oncology. This is a young field, and there's just some extraordinary people, many of them real true heroes, and Otis has his figure on the pulse of that. DAVID JOHNSON: Yeah, that's why he's been in some of the right places at the right time, and we'll hear more about that in this segment coming up now. PATRICK LOEHRER: Now Otis has had a career in many different areas, including ODAC, the NCI, the ACS, now at Hopkins. So let's hear a little bit more about Dr. Brawley's experience at the American Cancer Society and particularly with his experience with the former CEO, John Seffrin. DAVID JOHNSON: Sounds great. [MUSIC PLAYING] OTIS BRAWLEY: John and I had a wonderful run at the American Cancer Society. Got to do a lot of things. Got to testify for the Affordable Care Act. Got to do some of the science to actually argue that the Affordable Care Act would help. And I was fortunate enough to be there long enough to do some of the science to show that the Affordable Care Act is helping. DAVID JOHNSON: Yeah, I mean actually all of the things you accomplished at the ACS are truly amazing. Let me ask you, just on a personal level, what did you like most about that job, and then what did you like least about that job? [LAUGHTER] OTIS BRAWLEY: I like the fact-- there were a lot of things I liked about that job. There were a couple hundred scientists and scientific support people that you got to work with. And I used to always say, I do politics so you can do science. And what I used to like the most, every Wednesday afternoon that I was in town, I would walk around just to watch those people think. I used to joke around and say, I'm just walking around to see who came to work today. But I really enjoyed watching them work and watching them think, and that was fun. Another fun aspect of the job was people used to call and ask a little bit about the disease that they are a family member would have. And sitting down with them on the phone in those days-- we didn't have Zoom-- and talking to them through their disease. Not necessarily giving them advice on what to do in terms of treatment, but helping them understand the biology of the disease or connecting them with someone who was good in their disease. And I happen to, by the way, have sent some patients to both of you guys. That was a lot of fun. Then the other thing, of course, was the fact that you could actually influence policy and fix things. I'll never forget sitting across from Terry Branstad, then the governor of Iowa, and convincing him that the right thing to do is to raise the excise tax on tobacco in Iowa. Being able to see that you're effective and to see that you're positively influencing things. The bad side, some of the politics. I didn't necessarily like how some of the money was being raised or where they were raising money from. I think that you have to have a certain standard in terms of where you accept money. And we always had that tension with the fundraisers. But it's also true-- and I will give them a nod-- you can't do the fun things unless you raise money. So I really truly enjoyed my time at the American Cancer Society. And by the way, a shout out to Karen Knudsen, who is the CEO running the American Cancer Society now. And I'm fully committed to helping the ACS and helping Karen be successful. DAVID JOHNSON: One of the things I read-- I think I read this that you had said that one of your proudest accomplishments was revising the ACS screening guidelines. Tell us just a little bit about that. OTIS BRAWLEY: Yeah, going all the way back to the early 1990s, I started realizing that a lot of these guidelines for screening, or back then, this is before the NCCN guidelines for treatment even, that were published by various organizations, including the American Cancer Society. We're almost the equivalent of-- get the impression that in the 1960s, it would have been a smoke-filled room. But you gather a bunch of people into a room, and they come up with, this is what we should be doing. Indeed, the American Cancer Society in 1991 endorsed annual PSA screening for prostate cancer based purely on getting a group of primarily urologists into a room, and that's what they came up with. There was very little review of the science. There really was no science at that time except the science to show that PSA screening found cancer. There were no studies to show that led to men benefiting in that they didn't die. Indeed, in 1991, there was no study to show that treatment of early prostate cancer saved lives. The study to show treatment of prostate cancer saves lives was first published in 2003, and the radiation saves lives in 1997, 1998. Surgery saves lives in 2003 and screening has a small effect published in 2009. But they started recommending it in 1991 in this almost smoke-filled room kind of atmosphere. When I got to the American Cancer Society, I started an effort, and we involved people from the National Academy of Medicine, we involved people from the NCCN, from the American Urological Association, the American Academy of Family Physicians, the American College of Physicians. And we got together in that almost smoke-filled room again, but the idea was, how do you make responsible guidelines? And we wrote that up into a paper guide widely accepted by all of the organizations, and it involves a review of the literature that is commissioned by someone. And they spend a long time reviewing the literature and writing a literature review. And then you have a group of experts from various fields to include epidemiology and screening, social work, someone who's had the disease. Not just the surgeons and medical oncologists who treat the disease but some population scientists as well. They sit down and they reveal all of the scientific data, and then they start coming up with, we recommend this. And then they rank how strong that recommendation is based on the data. We published this in 2013 in The Journal of the American Medical Association. I do think that was important, you're right. That's Otis trying to bring his policy and his belief in orthodox approach to science and bring it all together. PATRICK LOEHRER: So let me reflect a little bit more on something. There is a book that I also just recently read by Dax-Devlon Ross, and it's a book entitled, Letters to my White Male Friends, and it was a fascinating read to me. You have this public persona and professional persona of being an outstanding physician, clinician, public speaker. But what we the three of us have never really had the conversation today is we have much more interest now in DEI. One of our other speakers talked about the fact that there's a tax that is placed upon underrepresented minorities and academics. They are all expected to be on committees. They have to be doing different things. And so the things that they love to do, they can't do it because they have to represent their race or their gender or their ethnicity. OTIS BRAWLEY: I have been blessed and fortunate. There are problems, and there are huge burdens that Black doctors, and women doctors by the way, have to carry. I have been fortunate that I have skated through without a lot of that burden. Maybe it has to do with oncology, but I will tell you that I have been helped by so many doctors, men and women, predominantly white, but some Asian, Muslim, Jewish, Christian. I don't know if it's oncology is selective of people who want to give folks a fair shake and really believe in mentoring and finding a protege and promoting their career. I have been incredibly, incredibly fortunate. Now that I say that, there are doctors, minority doctors and women, who don't have the benefits and don't have the fortunes that I have had, and we all have to be careful for that. As I said early on, John Altman told me that I will thank him by getting more Blacks and women into the old boys club. And so that was his realizing that there is a-- or there was a problem. I think there still is a problem in terms of diversity. Now I have seen personally some of the problem more outside of oncology in some of the other specialties. More in internal medicine and surgery, for example. By the way, there are also some benefit. I did well in medical school in third and fourth year in medical school at the University of Chicago because there were a group of Black nurses who were held that I wasn't going to fail. The nurses took me under their wing and taught me how to draw blood, how to pass a swan. The first code I ever called, there was a nurse standing behind me with the check off list. And so there are some advantages to being Black as well. But there are some disadvantages. I've been very fortunate. My advice to Black physicians is to keep an open mind and seek out the folks in medicine who truly do want to help you and truly do want to mentor you. And for the folks who are not minority or not women in medicine, I say, try to keep an open mind and try to help everybody equally. PATRICK LOEHRER: Thank you. DAVID JOHNSON: I want to go back to your book for a moment. And again, for those who've not read it, I would encourage them to do. So it's a really honest book, I think, well-written. You made a comment in there-- I want to make sure I quote it near correctly. You said that improvement in our health care system must be a bottom up process. What do you mean by "bottom up?" OTIS BRAWLEY: Well, much of it is driven by demand from patients and other folks. The name of the book was, How We Do Harm. And the synopsis is there are bunch of people who are harmed because they don't get the care that they need. And there's a bunch of people who are harmed because they get too much medicine and too much care. And they rob those resources away from the folks who don't get care at the same time that they're harmed by being overtreated, getting treatments that they don't need. The other thing, if I can add, in American health care, we don't stress risk reduction enough. I used to call it "prevention." Some of the survivors convince me to stress "activities to reduce risk of disease." We don't do a lot in this country in terms of diet and exercise. We try to do some work somewhat successfully on tobacco avoidance. We need to teach people how to be healthy. And if I were czar of medicine in the United States, I would try to make sure that everybody had a health coach. Many of us go to the gym and we have a trainer. We need trainers to teach us how to be healthy and how to do the right things to stay healthy. That's part of the bottom up. And in terms of costs you know my last paper that I published from the American Cancer Society, I published purposefully, this is my last paper. Ahmedin Jemal who's a wonderful epidemiologist who I happen to have worked with when I was at the National Cancer Institute and again later in my career at the American Cancer Society, I pushed Ahmedin-- he publishes these papers, and we estimate x number of people are going to be diagnosed with breast cancer and y number are going to die. He and I had talked for a long time about how college education reduces risk of cancer death dramatically. If you give a college education to a Black man, his risk of death from cancer goes down to less than the average risk for a white American. There's something about giving people college education that prevents cancer death. I simply challenged Ahmedin, calculate for me how many people in the United States would die if everybody had the risk of death of college-educated Americans. And he came back with of the 600,000 people who die in any given year, 132,000 would not die if they had all the things from prevention through screening, diagnosis, and treatment that college-educated people. Just think about that-- 132,000. Then I started trying to figure out what drug prevents 132,000 deaths per year? And I couldn't think of one until recently, and it happens to be the coronavirus vaccine. Which ironically has shown itself to be the greatest drug ever created in all of medicine. But in cancer, there's no breakthrough drug that is more effective than just simply getting every human being the care from risk reduction and prevention all the way through treatment that every human being ought to be getting. The solution to some of that starts with fixing third grade and teaching kids about exercise, about proper diet. PATRICK LOEHRER: We're going to have to wind things up here. But real quickly, a book you would recommend? OTIS BRAWLEY: Skip Trump, who's someone that we all know, wonderful guy used to run Roswell Park Cancer Center, just published a book actually it's coming out in September called, Centers of the Cancer Universe, A Half Century of Progress Against Cancer. I got a preprint of that, and it is a great book. It talks about what we've learned in oncology over the last 50 years since Richard Nixon signed the National Cancer Act. Keep in mind, he declared war on cancer on December 23, 1971. So we have an anniversary coming up in December. PATRICK LOEHRER: I want to close. Another book, I read the autobiography of Frederick Douglass. It's a wonderful read. It really is good. There were some endorsements at the end of this book, and one of them was written by a Benjamin Brawley, who wrote this review in a book called, The Negro in Literature and Art in 1921. And Benjamin Brawley was writing this about Frederick Douglass, but I would like to have you just reflect a moment. I think he was writing it about you, and I'm just going to read this. He basically said, at the time of his death in 1895, Douglass had won for himself a place of unique distinction. Large of heart and of mind, he was interested in every forward movement for his people, but his charity embraced all men in all races. His mutation was international, and today, many of his speeches are found to be the standard works of oratory. I think if your great, great grandfather were here today, he would be so incredibly proud of his protege, Otis. And it's such a privilege and pleasure to have you join us today on Oncology, Etc. Thank you so much. OTIS BRAWLEY: Thank you. And thank both of you for all the help you've given me over the years DAVID JOHNSON: Great pleasure having you today, Otis. I want to also thank all of our listeners for tuning in to Oncology, Etc. This is an ASCO educational podcast. We really are here to talk about anything and everything. So we're looking for ideas. Please, if you have any suggestions, feel free to email us at [email protected] Thanks again, and remember, Pat has a face for podcasts. [MUSIC PLAYING] SPEAKER: Thank you for listening to this week's episode of the ASCO e-learning weekly podcasts. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

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