Interviews on research presented at the European Hematology Association 2023 Hybrid Congress, which took place June 8-11 in Frankfurt, Germany
Jennifer Brown, MD, PhD, Offers Insights on BTK, BCL-2 Inhibitors in CLL
Brown
Jennifer Brown, MD, PhD, spoke with Evidence-Based Oncology (EBO) during the 2023 European Hematology Association Congress in Frankfurt, Germany, about considerations for prescribing Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL-2) inhibitors to patients with chronic lymphocytic leukemia (CLL). Brown is the director of the Chronic Lymphocytic Leukemia Center and an institute physician at Dana-Farber Cancer Institute in Boston, Massachusetts.
EBO: In CLL, we are seeing the use of second-generation BTK inhibitors, use of BTK inhibition alongside BCL-2 inhibitors, and studies of third-generation BTK inhibitors. What are the key considerations for clinicians in selecting a therapeutic approach?
Brown: Right now, in the frontline setting in the United States, it’s really primarily continuous BTK inhibition with a second-generation inhibitor, essentially acalabrutinib (Calquence) or zanubrutinib (Brukinsa), vs time-limited therapy with venetoclax (Venclexta)/obinutuzumab (Gazyva). We don’t have approval yet for BTK or BCL-2 [inhibitors], and the data showed pretty similar progression-free survival for BTK/BCL-2 as for venetoclax/obinutuzumab. So, I think, at present, it’s really quite reasonable to stick with venetoclax/obinutuzumab as a time-limited regimen.
For patients with p53 aberration, we do favor [a] continuous BTK inhibitor. And for patients with mutated favorable risk IGHV [immunoglobulin heavy chain], I certainly favor time-limited therapy because they have a good likelihood of achieving undetectable MRD [minimal residual disease] and then a very prolonged remission off therapy.
For all the patients in between, it’s something of a long discussion—taking into account their particular risk factors, their goals, and desires. For example, often young patients are happy to come in a lot [and] do the extra work of a time-limited regimen, whereas sometimes the older patients, they don’t want to do that, they just want to go on a BTK inhibitor and more or less be done with their monitoring. And so all of these factors come into play. It’s a lengthy discussion with the patient, really.
Hans Lee, MD, Discusses Infection Risks of Bispecific Therapies for Patients With MM
Lee
Hans Lee, MD, spoke with Evidence-Based Oncology (EBO) at the European Hematology Association 2023 Congress in Frankfurt, Germany, about possible infection risks for patients with relapsed/refractory multiple myeloma (R/R MM) receiving bispecific therapies. Lee is an associate professor and director of multiple myeloma clinical research, Department of Lymphoma/Myeloma, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston.
EBO: What is the current understanding of infection risk in patients with R/R MM receiving bispecific therapies?
Lee: We know that patients with multiple myeloma at baseline are at increased risk for infection, particularly after successive lines of prior therapy, but we are seeing an increased infection rate, more than what we typically would probably see, in patients receiving bispecific T-cell antibodies in phase 1 and phase 2 trials reported to date. This is represented by an increase in the total number of infections but also the increase in the grade 3 or higher infection rate, as well as the rates of hypogammaglobulinemia, or decreased IgG [immunoglobulin G] levels, that we’re seeing in our patients getting bispecific T-cell antibody-based therapy.
EBO: Do some bispecific therapies offer reduced risk relative to other types of therapy for R/R MM?
Lee: We are getting more data with non-BCMA [B-cell maturation antigen] bispecific T-cell antibody-based therapies targeting GPRC5D and FcRH5, and there does seem to be a reduced risk with non-BCMA–targeting bispecific T-cell antibodies compared with those that target BCMA. And this may be in part related to the target itself and that BCMA probably has more biological relevance than GPRC5D and FcRH5. Hence, targeting BCMA through bispecific T-cell antibodies leads to more profound humoral immunodeficiency and subsequent hypogammaglobulinemia and potential infection risk as well.
Cellular Therapies in Lymphoma Bring Hope, but Optimizing Their Use Remains a Challenge
December 10th 2023Recent decades have seen marked improvements in hematological cancer outcomes and an expanded armamentarium of therapies, but novel treatments require updated strategies that are not always easy to fine-tune, according to presenters at the 2023 American Society of Hematology Annual Meeting and Exposition.
Read More
Understanding the Unmet Need for Therapies to Treat Rare Bile Duct Cancer
May 24th 2022On this episode of Managed Care Cast, we bring you an excerpt of an interview with a co-chair of the 2022 Cholangiocarcinoma Foundation (CCF) annual conference, held earlier this year, about the significant unmet therapy needs facing most patients with this rare cancer.
Listen
Dr Kathryn Lindley on Pregnancy-Related Cardiovascular Care Gaps and Training Initiatives
December 8th 2023Cardiologists need skills in risk assessment, contraception counseling, and hypertension management for pregnant patients, according to Kathryn Lindley, MD, FACC, Vanderbilt University Medical Center.
Read More