The FDA has recently expanded the label of venetoclax (Venclexta®, AbbVie Inc. and Genetech Inc.) to now include the treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), including those requiring initial therapy. Venetoclax is a targeted therapy that binds to the BCL-2 protein, which stimulates apoptosis—programmed cell death—in cancer cells. Matthew S. Davids, MD, MMSc, Assistant Professor at Harvard Medical School, and colleagues conducted earlier research on the safety and efficacy of venetoclax monotherapy in patients with relapsed/refractory CLL. In an interview with i3 Health, Dr. Davids shares insights regarding the implications of the recent FDA approval and gives advice to oncologists who administer venetoclax to their patients.
What is the most challenging aspect of treating patients with CLL?
Historically, a challenging aspect of treating CLL patients has been that the patients tend to be older and have medical co-morbidities. We have chemotherapy-based regimens that can be effective as initial therapy, but the disease will inevitably relapse. These chemotherapy approaches tend to not work nearly as well after the first time, and they can have significant toxicities, particularly in older patients.
Can you comment on the significance of the recent FDA approval of venetoclax for patients with CLL?
Venetoclax is a targeted oral therapy that was previously approved only for CLL patients who had already had prior treatment. The recent approval of venetoclax in combination with obinutuzumab as an initial therapy for CLL is a major advance for the field, as it provides us with the first chemotherapy-free frontline regimen with the potential for time-limited therapy.
What advice would you give to oncologists who administer venetoclax to patients with CLL or SLL?
If you are new to using venetoclax and/or obinutuzumab, you have to be careful to closely follow the label to ensure that you safely initiate the regimen. For example, patients need to be monitored for tumor lysis syndrome, and pre-medications need to be administered to patients receiving obinutuzumab to reduce the risk of infusion reactions.
What would you advise doctors to consider in balancing this treatment option against other options that they have for this condition?
Chemoimmunotherapy does still have a role as frontline therapy for a small subset of CLL patients, particularly younger patients with mutated immunoglobulin heavy chain variable gene segments (IGHV) disease, where the fludarabine/cyclophosphamide/rituximab (FCR) regimen has the potential to functionally cure. However, the majority of patients will benefit more from a novel-agent–based approach to frontline therapy. Ibrutinib is another oral therapy approved for frontline CLL treatment and can also be a great option for patients, though it requires continuous therapy to maintain remission. I think that doctors should discuss these options with their patients to help them weigh the pros and cons of each approach in order to help them decide what the best regimen is for them individually.
About Dr. Davids
Matthew S. Davids, MD, MMSc, is an Assistant Professor of Medicine at Harvard Medical School and the Associate Director for the Center for Chronic Lymphocytic Leukemia. Dr. Davids works as a physician at Dana-Farber Cancer Institute. His clinical interests include CLL and non-Hodgkin lymphoma.
For More Information
Davids MS, Hallek M, Wierda W, et al (2018). Comprehensive safety analysis of venetoclax monotherapy for patients with relapsed/refractory chronic lymphocytic leukemia. Clin Cancer Res, 24(18):4371-4379. DOI:10.1158/1078-0432.CCR-17-3761
Roberts AW, Davids MS, Pagel JM, et al (2016). Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med, 374:311-322. DOI:10.1056/NEJMoal1513257
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily represent the views of i3 Health.