Dr Dorritie on the Clinical Implications of the 5-Year Follow-Up Data From CAPTIVATE in CLL/SLL

“No patients developed a BTK mutation or a PLCG2 mutation, which is really reassuring, because we do know that patients who stay on BTK inhibitors for a longer period of time are at risk of developing those mutations.”

Kathleen A. Dorritie, MD, hematologist/medical oncologist, the University of Pittsburgh Medical Center’s Hillman Cancer Center; assistant professor, medicine, Division of Oncology, Department of Medicine, University of Pittsburgh, discusses 5-year of follow-up data from the phase 2 CAPTIVATE trial (NCT02910583) in patients with chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma.

This investigation evaluated first-line, fixed-duration ibrutinib (Imbruvica) plus venetoclax (Venclexta), which continued to elicit clinically meaningful progression-free survival and deep remissions, according to the follow-up data, which were shared at the 2023 ASH Annual Meeting. This 5-year follow-up provides valuable insights into the combination’s efficacy and potential to mitigate resistance mechanisms associated with single-agent targeted therapies, Dorritie begins.

At up to 5.5 years of follow-up, with a median follow-up of 61.2 months (range, 0.8-66.3), the 5-year PFS rate was 67%. Most of the patients who progressed did so mostly after the 2-year treatment cutoff, she reports. Encouragingly, among patients who required retreatment, most responded effectively, she adds. This indicates that fixed-duration therapy may offer an effective approach to limit prolonged exposure to these agents, reducing toxicity and delaying the emergence of resistance mutations, Dorritie explains. The ability to achieve a robust response upon retreatment adds further support for this strategy, demonstrating that patients can still derive substantial benefit when therapy is resumed, she emphasizes.

Additionally, the development of resistance mutations was notably rare in this study, according to Dorritie. Among the cohort of patients who experienced disease progression, only one developed a BCL2 mutation, with no observed cases of BTK or PLCG2 mutations, she continues. This is reassuring given the known risks of resistance mutations associated with prolonged use of BTK inhibitors, she says. These findings highlight the potential of fixed-duration ibrutinib plus venetoclax to maintain disease control and simultaneously minimize long-term risks, offering a balanced treatment approach for patients with CLL, Dorritie concludes.