S14 Ep72: CLL Treatment Paradigm Shifts With Evolving Treatment Sequencing and BTK Inhibition: With Joanna M. Rhodes, MD, MSCE; and Krish Patel, MD

In today’s episode, the discussion features Joanna M. Rhodes, MD, MSCE, director of Lymphoma and systems head for Lymphoma at Rutgers Cancer Institute of New Jersey and RWJBarnabas Health, alongside Krish Patel, MD, director of Lymphoma Research and executive chair of the Lymphoma Research Executive Committee at the Sarah Cannon Research Institute. Together, they discussed how the chronic lymphocytic leukemia (CLL) treatment paradigm continues to evolve with advances in targeted therapy. In this exclusive interview, Drs Rhodes and Patel highlighted key disease- and patient-related factors that guide first-line treatment selection, considerations that influence sequencing decisions in later lines of therapy, and how hematologists determine the optimal timing to transition between treatments. They also discussed the clinical distinctions between covalent and noncovalent BTK inhibitors, the current role of pirtobrutinib (Jaypirca) in CLL management, and how its safety profile and emerging data may inform future use earlier in the treatment course. The conversation concluded with reflections on the CLL data presented at the 2025 ASH Annual Meeting that were most relevant to clinical practice. nd many of your other favorite podcast platforms,* so you get a notification every time a new episode is posted. While you are there, please take a moment to rate us!

In today’s episode, the discussion features Christof Vulsteke, MD, PhD, head of the Integrated Cancer Center Ghent in Belgium, who provided clinical and regulatory insight into the KEYNOTE-905 study (NCT03924895) and the November 2025 FDA approval of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC). In this exclusive interview, Dr Vulsteke outlined the scientific rationale and study design of KEYNOTE-905, reviewed the key efficacy and safety findings observed with the enfortumab vedotin/pembrolizumab combination, and discussed how the safety profile of this combination aligns with prior experience in bladder cancer. He also contextualized the significance of this FDA approval in addressing a longstanding unmet need for cisplatin-ineligible patients and highlighted remaining gaps in care, including global access, patient selection, and future research directions aimed at improving outcomes in this challenging-to-treat population.

In today’s episode, we sat down with Julia Rotow, MD, and Gavitt Woodard, MD, to talk through recent updates to the perioperative non–small cell lung cancer treatment paradigm. 

In today’s episode, we passed the mic to Kathryn S. Nevel, MD; and Michael Veronesi, MD, PhD, who led an OncLive Ask the Expert discussion on evolving imaging strategies in glioma. 

In today’s episode, we had the pleasure of speaking with Jason Mouabbi, MD, about the role of circulating tumor DNA (ctDNA) testing in early-stage breast cancer management. Dr Mouabbi is an assistant professor in the Department of Breast Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston. In our exclusive interview, Dr Mouabbi highlighted the ways that ctDNA has evolved from a research tool to a potential clinical decision-making aid in breast cancer, data suggesting that ctDNA negativity after neoadjuvant therapy can be more predictive of long-term outcomes than pathologic complete response, and the importance of offering ctDNA testing to patients and discussing the benefits of this emerging approach.

In today’s episode, we had the pleasure of speaking with Pooja M. Phull, MD, a hematologist/oncologist at the John Theurer Cancer Center at Hackensack University Medical Center in New Jersey, about emerging insights into the gut microbiome and its clinical relevance in multiple myeloma. Dr Phull discussed how microbial composition—particularly the presence of butyrate-producing bacteria—may influence therapeutic responsiveness, sustained minimal residual disease negativity, and long-term outcomes for patients undergoing autologous stem cell transplantation. In our exclusive interview, Dr Phull reviewed findings from a translational study that longitudinally profiled the fecal microbiome of patients with newly diagnosed myeloma, highlighting the significant post-transplant depletion of beneficial short-chain, fatty acid–producing organisms and its association with inferior progression-free survival. She also outlined supportive laboratory and in vivo data demonstrating the antitumor effects of butyrate and discussed how microbiome profiling may serve as both a predictive biomarker and a potential therapeutic target. Additionally, Dr Phull explored how dietary patterns, lifestyle factors, and antibiotic stewardship may contribute to preserving gut microbial health, and she emphasized the growing need for prospective studies to clarify how these interventions could enhance treatment outcomes for patients with active myeloma and precursor conditions such as monoclonal gammopathy of undetermined significance and smoldering myeloma.

In today’s episode, we had the pleasure of speaking with Edward S. Kim, MD, MBA; and Jyoti Malhotra, MD, MPH, about the promise of IB6 as a therapeutic target in non–small cell lung cancer (NSCLC) management. Dr Kim is physician-in-chief of City of Hope Orange County, vice physician-in-chief of the City of Hope National Medical Center, and a professor in the Department of Medical Oncology & Therapeutics Research at City of Hope in Irvine, California. Dr Malhotra is interim division chief of Thoracic Medical Oncology, an associate professor in the Department of Medical Oncology & Therapeutics Research, and the director of Thoracic Medical Oncology at City of Hope. In our exclusive interview, Drs Kim and Malhotra discussed factors that make IB6 unique compared with other NSCLC biomarkers, the prevalence of IB6 expression among patients with lung cancer, and the rationale for investigating sigvotatug vedotin (formerly SGN-B6A) vs docetaxel in patients with previously treated NSCLC in the phase 3 Be6A Lung-01 trial (NCT06012435). 

Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago. In this episode, OncLive On Air® partnered with Two Onc Docs to highlight chronic lymphocytic leukemia (CLL) updates from the 2025 ASH Annual Meeting. Drs Armstrong and Tawagi noted that CLL is typically diagnosed in asymptomatic, elderly individuals presenting with lymphocytosis. A definitive diagnosis is established by confirming the clonality of circulating B lymphocytes via immunoglobulin light chain restriction on flow cytometry, they explained. Treatment initiation is reserved for active disease, which is indicated by B symptoms, progressive cytopenias, threatened organ function, or bulky disease such as splenomegaly, they said. They continued by reporting several prognostic features that denote poor outcomes. Current standard frontline regimens use covalent BTK inhibitors or time-limited targeted regimens that include venetoclax (Venclexta), often combined with an anti-CD20 monoclonal antibody, according to the experts. They added that TKI-based therapy is preferred for patients with high-risk features. The phase 3 BRUIN CLL-313 trial (NCT05023980) investigated pirtobrutinib (Jaypirca), a highly selective noncovalent BTK inhibitor, compared with bendamustine and rituximab (BR) in patients with treatment-naive CLL. The trial showed a significant improvement in progression-free survival with pirtobrutinib vs BR. Pirtobrutinib was also associated with a favorable safety profile, with modest rates of class-associated toxicities, including all-grade bleeding, arthralgia, and atrial fibrillation. Although pirtobrutinib showed superior efficacy in BRUIN CLL-313, the clinical interpretation of these data is complicated because BR is an outdated control arm compared with contemporary frontline standards, Armstrong and Tawagi emphasized. Furthermore, the requirement for indefinite therapy with BTK inhibitors is a sequencing challenge, particularly as pirtobrutinib is currently approved in the post-covalent BTK inhibitor setting, they continued. However, its favorable toxicity profile suggests potential utility in elderly patients with pre-existing cardiovascular comorbidities, they noted. Future studies are focused on comparing pirtobrutinib vs time-limited venetoclax and evaluating various triplet regimens, they concluded.

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilcon Family Chair at the Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. In this episode, Dr Matulonis sat down with guest Panagiotis (Panos) A. Konstantinopoulos, MD, PhD, to discuss the different subtypes of endometrial cancer and treatment developments for this disease. Dr Konstantinopoulos is the director of Translational Research in the Division of Gynecologic Oncology, the director of the Mellen and Eisenson Family Center for BRCA and Related Genes, and the Velma Eisenson Chair for Clinical and Translational Research at Dana-Farber Cancer Institute; as well as a professor of medicine at Harvard Medical School. Drs Matulonis and Konstantinopoulos explained that patients with mismatch repair–deficient (dMMR) tumors substantially benefit from a decreased risk of progression or death when immunotherapy is added to standard therapy. They noted that immunotherapy appears important for the management of dMMR tumors, even those in earlier stages or in patients who have no measurable disease remaining after surgery. For MMR-proficient (pMMR) tumors, Drs Matulonis and Konstantinopoulos highlighted that PD-1 blockade combined with chemotherapy improves survival vs chemotherapy alone, but that this benefit is not as substantial as that seen in dMMR disease. Crucially, they reported that if a pMMR tumor has no measurable disease after surgery, adding immune checkpoint blockade does not appear beneficial. They stated that tailored treatment approaches are key for managing pMMR disease subtypes. They added that hormonal therapy may be used upfront for slow-growing, estrogen receptor–positive metastatic disease. They continued by saying that DNA damage and replication stress are critical targets, particularly in p53-mutated tumors, like uterine serous cancers. Furthermore, they stressed that although the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (Enhertu) is highly effective in HER2-positive tumors, treatment with this agent requires monitoring for toxicities, including interstitial lung disease and decreased ejection fraction.

In this episode, Gregory J. Tiesi, MD, FACS, FSSO, hosted a discussion about the use of hepatic artery infusion (HAI) in colon cancer and liver cancer management. Dr Tiesi is the medical director of Hepatobiliary Surgery at the Hackensack Meridian Jersey Shore University Medical Center in Neptune, New Jersey. He was joined by: Anthony Scholer, MD, FACS, FSSO, a surgical oncologist specializing in hepatobiliary surgery, at Hackensack Meridian Medical Group and Jersey Shore University Medical Center in Neptune, New Jersey Benjamin Jon Golas, MD, FACS, regional chief of Surgical Oncology for Hackensack Meridian Health’s Central Region, surgical director of Oncology Services at Jersey Shore University Medical Center, vice chair of Surgery at Jersey Shore University Medical Center Cancer Surgery, and an associate professor of surgery at the Hackensack Meridian School of Medicine in Nutley, New Jersey Eric Pletcher, MD, a surgeon specializing in Complex General Surgical Oncology at Hackensack Meridian JFK University Medical Center in Edison Drs Tiesi, Scholer, Golas, and Pletcher explained that HAI is a longstanding regional therapy used for treating primary and metastatic tumors to the liver, notably unresectable colorectal liver metastases and intrahepatic cholangiocarcinoma. The physiologic mechanism of this treatment leverages the dual blood supply of the liver, capitalizing on the fact that these malignancies primarily derive their perfusion from the hepatic artery, the experts noted. They emphasized that by delivering chemotherapeutic agents, such as floxuridine, directly via the gastroduodenal artery, HAI concentrates drug exposure at the tumor site, maximizing antitumor effect and minimizing extrahepatic toxicity.  They explained that patient selection requires fitness for surgery and good liver function, excluding those with cirrhosis or portal hypertension. They also noted that the procedure involves implanting a subcutaneous pump, followed by rigorous intraoperative and postoperative nuclear medicine studies to confirm the absence of extrahepatic perfusion. Evidence supports that HAI combined with systemic therapy achieves higher intrahepatic objective responses, improves local disease control, and enhances conversion to resectability, correlating with improved long-term survival, the experts reported. However, potential complications include pump pocket infections, biliary sclerosis, and gastric ulcers, they added. The experts concluded by highlighting that establishing an HAI program necessitates a robust, multidisciplinary approach involving surgical oncology, medical oncology, and interventional radiology.