AAV gene therapy in hemophilia: progress, challenges and what comes next

This episode of the VJHemOnc podcast, featuring Manali Kamdar, MD, University of Colorado Cancer Center, Denver, CO, focuses on the practical use of BTK inhibitors (BTKis) in non-Hodgkin lymphoma (NHL). Dr Kamdar begins by discussing which factors guide patient selection for BTKi therapy and outlines how to choose among available agents. She then shares valuable insights on toxicity management, approaching patients with cardiovascular comorbidities, and monitoring treatment response and progression. Finally, Dr Kamdar leaves community physicians with three practical takeaways for successfully using BTKis in everyday clinical practice.

This VJHemOnc podcast explores the evolving role of gene therapy in hemophilia, focusing on the challenges of AAV-based approaches and the development of next-generation strategies. Radek Kaczmarek, PhD, Indiana University School of Medicine, Indianapolis, IN, discusses the limitations of AAV gene therapy in hemophilia A, including factor VIII engineering, durability, and liver toxicity. He also examines potential malignancy risks associated with AAV integration and the importance of long-term surveillance following treatment. Finally, Dr Kaczmarek discusses emerging non-AAV approaches, including lentiviral gene therapy, targeted gene insertion, and gene editing, and their potential to address some of the limitations of current gene therapy approaches.

This VJHemOnc podcast explores the evolving management of mantle cell lymphoma (MCL), from assessing patient fitness to sequencing therapy after BTK inhibitor progression. Tycel Phillips, MD, FASCO, City of Hope, Duarte, CA, and Yasmin Karimi, MD, University of Michigan, Ann Arbor, MI, discuss assessing fitness and frailty, while Craig Portell, MD, University of Virginia, Charlottesville, VA, outlines the multidisciplinary approach to MCL care. Nirav Shah, MD, Medical College of Wisconsin, Milwaukee, WI, reviews frontline sequencing, including using MRD status to guide transplant decisions, and Dr Phillips and Dr Portell discuss managing patients with higher-risk disease features. Dr Portell also addresses toxicity and treatment burden with long-term BTK inhibitor use. To conclude, Manali Kamdar, MD, University of Colorado Cancer Center, Denver, CO, and Dr Karimi highlight emerging options after BTK inhibitor progression, including non-covalent BTK inhibitors, BCL2 inhibitors, CAR T-cell therapy, and bispecific antibodies.

This VJHemOnc podcast explores the evolving treatment landscape in multiple myeloma, focusing on treatment selection and sequencing across the disease course. Fredrik Schjesvold, MD, PhD, Oslo University Hospital, Oslo, Norway, discusses shared decision-making in frontline treatment, while Peter Voorhees, MD, Levine Cancer Institute, Charlotte, NC, explores sequencing CAR T-cell therapies and bispecific antibodies, including the choice between BCMA- and GPRC5D-directed approaches. Rahul Banerjee, MD, FACP, Fred Hutchinson Cancer Center, Seattle, WA, reviews updated findings from the MajesTEC-3 trial (NCT05083169) of teclistamab plus daratumumab in high-risk disease, and Peter Voorhees discusses Phase III MonumenTAL-3 (NCT05455320) data evaluating talquetamab plus daratumumab, with or without pomalidomide. Efstathios Kastritis, MD, University of Athens School of Medicine, Athens, Greece, highlights strategies for managing infections associated with bispecific antibodies, while Mohamad Mohty, MD, PhD, Saint-Antoine Hospital, Paris, France, discusses the transition towards community-based delivery of bispecific therapies.

There has been a significant shift in the treatment of acute lymphoblastic leukemia (ALL), driven by the emergence of novel immunotherapies. In this episode, leading experts explore how these advances are changing the treatment landscape and where the field is headed next. First, Marlise Luskin, MD, MSCE, Dana-Farber Cancer Institute, Boston, MA, outlines emerging treatment strategies for ALL and highlights the potential to reduce reliance on intensive chemotherapy by integrating novel therapies into clinical practice. Then, Martin Schrappe, MD, FRCP, University Medical Center Schleswig-Holstein, Kiel, Germany, shares insights into a trial evaluating blinatumomab as a replacement for high-dose chemotherapy in pediatric patients with newly diagnosed high-risk ALL. Following this, you will hear a discussion from the 8th International Workshop on CAR-T and Bispecifics, in which Ibrahim Aldoss, MD, City of Hope, Duarte, CA, and Bijal Shah, MD, Moffitt Cancer Center, Tampa, FL, provide updates on T-cell engagers and CAR T-cell therapy in ALL. To conclude the episode, Nicola Maciocia, MBChB, PhD, University College London Hospitals NHS Foundation Trust, London, UK, discusses advances in CAR-T for T-cell ALL and comments on whether cellular immunotherapy may be the most promising approach to curing this leukemia subtype.

This VJHemOnc podcast explores how precision medicine is reshaping the management of myelodysplastic syndromes (MDS). Alex Bataller, MD, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses whole genome sequencing, patient selection for venetoclax-based therapy, and the future of precision medicine following the VERONA trial (NCT04401748). Pinkal Desai, MD, MPH, Weill Cornell Medicine, New York, NY, reviews the evolving role of luspatercept, while Sophie Park, MD, PhD, CHU Grenoble Alpes, Grenoble, France, presents Phase III EPO-PRETAR (NCT03223961) findings. Mika Kontro, MD, PhD, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland, discusses updated BEXMAB trial (NCT05428969) results of bexmarilimab plus azacitidine. Thomas Cluzeau, MD, PhD, Central University Hospital of Nice, Nice, France, explores TP53-mutated MDS, and Eytan Stein, MD, Memorial Sloan Kettering Cancer Center, New York, NY, highlights first-in-human data for the CLK inhibitor BH-30236 in relapsed or refractory AML and higher-risk MDS.

This episode of the VJHemOnc podcast explores the current and future role of BTK inhibition across several non-Hodgkin lymphoma (NHL) subtypes. First, Charalampia Kyriakou, MD, PhD, University College London Hospitals NHS Trust (UCLH), London, UK, Steven Treon, MD, PhD, FRCP, Dana-Farber Cancer Institute, Boston, MA, and Anna Maria Frustaci, MD, Niguarda Hospital, Milan, Italy, provide insight into the established role of BTK inhibitors (BTKis) in Waldenström's macroglobulinemia (WM). Following this, Krish Patel, MD, Sarah Cannon Research Institute, Nashville, TN, Manali Kamdar, MD, University of Colorado Cancer Center, Denver, CO, and Tycel Phillips, MD, FASCO, City of Hope, Duarte, CA, discuss the shift of BTKis to the frontline setting in mantle cell lymphoma (MCL), and outline therapeutic approaches being evaluated for patients who relapse on these agents. Next, Alexey Danilov, MD, PhD, City of Hope, Duarte, CA, highlights why BTKis have not had the same impact in follicular lymphoma (FL) as in other B-cell malignancies, and comments on their current role in this disease, before Paolo Strati, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the value of newer-generation BTK inhibitors in relapsed/refractory (R/R) indolent B-cell lymphoma. To conclude, Dr Kamdar shares insight into the potential role of BTKis in diffuse large B-cell lymphoma (DLBCL).

In this episode of the VJHemOnc podcast, Daan Dierickx, MD, PhD, KU Leuven and University Hospitals Leuven, Leuven, Belgium, shares insight into the diagnosis and management of hematologic malignancies during pregnancy. Dr Dierickx comments on common misconceptions clinicians may have when treating this patient population and outlines key principles and factors that guide clinical decisions for pregnant patients to optimize outcomes for both the mother and the baby. He then discusses the current approach to managing specific malignancies during gestation, including acute leukemias, Hodgkin and non-Hodgkin lymphoma, myeloproliferative neoplasms (MPNs), and multiple myeloma. 

This VJHemOnc podcast explores the latest advances in Hodgkin lymphoma, from evolving frontline treatment strategies to emerging approaches in relapsed and refractory disease. Graham Collins, MA, MBBS, MRCP, FRCPath, DPhil, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, discusses the final three-year results from the AVENUE study (NCT03617666) and the role of circulating tumor DNA (ctDNA) in guiding treatment de-escalation. Stephen Ansell, MD, PhD, Mayo Clinic, Rochester, MN, compares BrECADD and Nivo-AVD for advanced-stage disease, while Sven Borchmann, MD, University Hospital Cologne, Cologne, Germany, highlights the prognostic value of ctDNA-based measurable residual disease assessment. Guilherme Perini, MD, Hospital Israelita Albert Einstein, São Paulo, Brazil, reviews the Phase II KEYFORM-008 trial (NCT05508867) investigating dual LAG-3 and PD-1 blockade in relapsed or refractory classical Hodgkin lymphoma, and Cathy Burton, MB BChir, MD, MRCP, FRCPath, St James's University Hospital, Leeds, UK, discusses treatment sequencing after checkpoint inhibition and the evolving role of autologous stem cell transplantation.

This podcast explores sequencing strategies and treatment considerations for BTK inhibitors in chronic lymphocytic leukemia (CLL). Jennifer Brown, MD, PhD, Dana-Farber Cancer Institute, Boston, MA, discusses treatment options following covalent BTK inhibitor therapy, including venetoclax-based regimens and non-covalent BTK inhibitors. Gianluca Gaidano, MD, PhD, University of Eastern Piedmont, Vercelli, Italy, examines treatment selection after BTK inhibitor therapy, the improved safety profile of second-generation BTK inhibitors, and the Phase III AMPLIFY trial (NCT03836261) evaluating fixed-duration acalabrutinib plus venetoclax. Barbara Eichhorst, MD, University Hospital Cologne, Cologne, Germany, reviews the CLL-FRAIL study investigating continuous acalabrutinib in older and frail patients with CLL. Kerry Rogers, MD, The Ohio State University, Columbus, OH, discusses strategies to overcome BTK inhibitor resistance, including fixed-duration combinations and long-term follow-up from a Phase II study of venetoclax plus ibrutinib in patients with BTK inhibitor resistance mutations. Finally, Matthew Davids, MD, Dana-Farber Cancer Institute, Boston, MA, presents findings from the Phase III BRUIN CLL-322 trial (NCT06073821) evaluating fixed-duration pirtobrutinib, venetoclax, and rituximab in previously treated CLL.