The HemOnc Pulse

In this episode of The HemOnc Pulse, Grzegorz Nowakowski MD, a Professor of Oncology and Medicine in the Division of Hematology at the Mayo Clinic, recounts his experience serving on the FDA Oncologic Drugs Advisory Committee that reviewed and evaluated data from the POLARIX study and polatuzumab vedotin-piiq (Polivy)for patients with previously untreated LBCL.

In this episode of The HemOnc Pulse, Dr. Maddocks, Professor of Clinical Internal Medicine in the Division of Hematology at The Ohio State University, charts the treatment evolution of mantle cell lymphoma (MCL) from frontline therapy to future directions. She also explains her initial shock, and subsequent bittersweet reaction to the withdrawal of ibrutinib.

Dr. Cortes, who serves as Director of the Georgia Cancer Center at Augusta University, joins host Chadi Nabhan, MD, MBA, FACP, to chat about the “boom” in treatments for chronic myeloid leukemia (CML), and where he sees a need for balance. Dr. Cortes discussed the evolution of tyrosine kinase inhibitors (TKIs) and the multiple generations of TKIs that are now available. Second-generation TKIs can lead to earlier and deeper responses than first-generation TKIs, he said, noting that this means patients receiving second-generation TKIs are more likely to be able to discontinue treatment. “If I was diagnosed with CML, I would take a second-generation TKI,” Dr. Cortes said. However, Dr. Cortes emphasized that the first-generation TKI imatinib comes with a lower risk of serious side effects than second-generation TKIs. This is an important consideration because “most people are going to do well and have a normal life expectancy” on imatinib, he said. It is critical to evaluate multiple factors when choosing between a first-generation TKI and a second-generation TKI. This means involving patients in the decisions about treatment to ensure they are comfortable with the balance of efficacy and safety, he said. “I certainly would rather have more bags under my eyes than a heart attack,” Dr. Cortes said. “So, we need to balance that, and I think that sometimes we've been a little too obsessed on [obtaining] the lowest possible [polymerase chain reaction] value, and we lose the context of other elements that are important, such as risks, and comorbidities and side effects.” He also discussed a population of patients who remain challenging to treat despite the evolution of therapies for CML. “The most difficult patient is one without a mutation,” Dr. Cortes said, noting this is because response rates are lowest for those without a mutation and “you don’t know why they are not responding.”

Dr. Elias Jabbour, an Associate Editor of Blood Cancers Today, discusses the burning questions in acute lymphoblastic leukemia (ALL). Topics include approaches to treating Philadelphia-negative ALL, measuring MR-D in pH negative disease, treatment options for both younger and older patients with pH negative leukemia, and current treatment options for relapsed disease in ALL.

Dr. Rafael Fonseca, an expert in multiple myeloma treatment, discusses the future of MM treatment, the debate between CAR-T therapies and bispecifics, the role of measurable residual disease (MRD), the potential for bispecific therapies to democratize access to advanced treatments, and the paradigm shift toward prioritizing deeper responses, including MRD negativity, for long-term cure in myeloma patients.

On this episode of The HemOnc Pulse, guest Jonathan Friedberg, MD, MMSc, a hematologic oncologist at the University of Rochester Medicine – Wilmot Cancer Institute, chats with host Dr. Chadi Nabhan on the subtle but important shift in the treatment landscape of diffuse large B-cell lymphoma (DLBCL)in the post-POLARIX trial era. The POLARIX trial, which was designed to improve upon the standard R-CHOP regimen for DLBCL treatment, investigated the potential of polatuzumab vedotin. The phase III trial ultimately resulted in the US Food and Drug Administration approving the treatment in previously untreated DLBCL, not otherwise specified, or high-grade B-cell lymphoma. The approval is for patients with an International Prognostic Index (IPI) score of two or greater. "I think that this was a robustly done randomized placebo-controlled trial that showed a small but clinically significant benefit as far as progression-free survival in patients with IPI score of two and above [in] large B cell lymphoma," he said.

Guillermo Garcia-Manero, MD, of the University of Texas MD Anderson Cancer Center, joins Chadi Nabhan, MD, MBA, FACP, live at the Eleventh Annual Meeting of the Society of Hematologic Oncology to discuss the phase III COMMANDS trial, the recent approval of luspatercept, and other developments in myelodysplastic syndromes (MDS) treatment and research. Dr. Garcia-Manero spoke about the design of the phase III COMMANDS trial, which evaluated luspatercept versus epoetin alfa for the treatment of anemia in patients with lower-risk MDS who required red blood cell (RBC) transfusions but had not previously received an erythropoiesis-stimulating agent. “The study is very interesting in that it's very well controlled … and the data [are] very clear,” he said. The phase III trial showed 58.5% of patients receiving luspatercept achieved the primary endpoint of RBC transfusion independence for at least 12 weeks with a mean hemoglobin increase of at least 1.5 g/dL within the first 24 weeks, while this was only reported in 31.2% of patients receiving epoetin alfa.

Dr. Shadman of the Fred Hutchinson Cancer Center in Seattle rounds up the latest news in chronic lymphocytic leukemia (CLL) from the summer conferences, including updates on novel Bruton tyrosine kinase inhibitor (BTKi) therapies in CLL.

In this episode of The HemOnc Pulse, Dr. Bhatnagar, an Associate Professor of Medicine at the West Virigina University Cancer Institute, reflects on how the molecular characterization of acute myeloid leukemia (AML) has evolved. She joins host Chadi Nabhan, MD, MBA, FACP, to discuss how this growing base of knowledge has impacted diagnosis, treatment, and classification. “The most significant changes have come about as a result of improvements and refinements in the molecular characterization of AML,” Dr. Bhatnagar said. Some of these changes include major updates in the World Health Organization and European LeukemiaNet systems. The episode also highlights Dr. Bhatnagar’s recent research, which explored the differential impact of mutations by race in patients with AML. While questions remain, she outlined future research that may help explain some disparities in AML outcomes.

Is there a venetoclax combination that reigns supreme in chronic lymphocytic leukemia (CLL)? Is venetoclax-based therapy the way to go in treating frontline CLL? Nitin Jain, MD, of the University of Texas MD Anderson Cancer Center, shares his thoughts on these questions and recent data published in the New England Journal of Medicine.