Counseling Patients on BTK Plus BCL2 Combination Therapy: Safety and Disease Considerations

In this segment, Drs. Brander and Flinn discuss the practical considerations for counseling CLL patients receiving the combination of a BTK inhibitor, specifically zanubrutinib, with venetoclax. Dr. Flinn emphasizes the need to balance efficacy with safety when presenting treatment options. Patients receiving venetoclax may experience neutropenia and an increased risk of infections, but the advantage of a fixed-duration regimen is that adverse events typically resolve once therapy is completed. BTK inhibitors, if used in fixed duration, limit cumulative exposure and reduce the likelihood of long-term side effects such as atrial fibrillation and hypertension. He highlights that zanubrutinib appears to have a favorable safety profile, making it a suitable partner for venetoclax in combination therapy.

Dr. Brander adds that individual disease characteristics should guide therapy selection. Patients with bulky lymphadenopathy or symptomatic disease may benefit from a BTK inhibitor lead-in, which helps reduce tumor burden before adding venetoclax and mitigates the risk of tumor lysis syndrome. This approach also allows for a deeper response in both blood and nodal compartments, which might not be achieved with venetoclax alone in certain patients.

Dr. Flinn notes the importance of all-oral regimens for patient convenience, avoiding infusion-related complications associated with therapies like obinutuzumab. The BTK lead-in not only facilitates safer venetoclax administration but also improves tolerability for patients with extensive disease.

The discussion underscores that therapy selection involves a nuanced assessment of disease burden, risk profile, and patient preference, in addition to the expected safety profile. Combining BTK inhibitors with BCL2-targeted therapy can be particularly beneficial for patients with high disease burden, symptomatic lymphadenopathy, or a need for a rapid and deep response, highlighting the importance of individualized treatment planning in CLL.