Dr Koff on BTK Inhibitors vs Venetoclax-Based Regimens in First-Line CLL

Jean L. Koff, MD, MS, associate professor, Department of Hematology and Medical Oncology; clinical investigator, Bone Marrow and Stem Cell Transplant Center, Emory University School of Medicine; member, Discovery and Developmental Therapeutics Research Program, Winship Cancer Institute, Emory University, discusses the considerations for deciding between BTK inhibitors vs venetoclax (Venclexta)-based regimens in the first-line treatment of patients with chronic lymphocytic leukemia (CLL).

Koff explains that both therapeutic options offer strong overall response rates (ORRs) and durable remissions; however, BTK inhibitors and venetoclax have present adverse effect (AEs) profiles and treatment administration schedules, which are crucial factors in clinical decision-making.

Treatment with BTK inhibitors is typically indefinite, requiring patients to adhere to a daily oral regimen, she says. This continuous treatment approach is well-suited for patients who prefer the convenience of a daily pill to maintain long-term control of their CLL, Koff explains. However, continuous treatment with BTK inhibitors could result in cumulative AEs, including cardiovascular toxicity, bleeding risks, and potential development of resistance over time, which require careful monitoring and management by clinicians, Koff notes.

Conversely, venetoclax-based regimens offer a time-limited therapy, which are typicallys completed within a 2-year period, Koff continues. This option can be appealing to patients who prefer a defined treatment duration. During the first 6 months of treatment, venetoclax-based regimens require a ramp-up period with close monitoring to mitigate the risk of AEs, Koff says. Some venetoclax-based regimens, such as venetoclax plus azacitidine, could require an agent to be given as an infusion, which necessitates hospital visits for patients, Koff adds.

Choosing between these regimens should be a joint decision between clinicians and patients, accounting for the patient’s treatment preferences, says Koff. Although some patients may prioritize the long-term control provided by BTK inhibitors despite the need for indefinite treatment, others may value the finite course of venetoclax despite the initial intensity of the regimen.

Ultimately, a thorough discussion with patients about these options allows for a more individualized treatment approach, optimizing outcomes and aligning with patients’ lifestyles and treatment goals, Koff concludes.