Exploring the Efficacy and Safety of Ibrutinib and Venetoclax in CLL

At the recent European Hematology Association 2024 Congress, Ryan Jacobs, MD, lymphoma division director at Atrium Health Levine Cancer Institute, presented updated data from CAPTIVATE, a multicenter, phase 2 study with 2 patient cohorts that assessed outcomes among patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

In part 1 of our interview with him, he explained how these long-term data show that a majority of patients with CLL had stable disease after 4.5 years of follow-up. These data were presented in the abstract “Outcomes in High-Risk Subgroups After Fixed-Duration Ibrutinib + Venetoclax for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Up to 5.5 years of Follow-Up in the Phase 2 CAPTIVATE Study.”

Here in part 2, he explains the importance of CAPTIVATE’s design and the primary goals of the investigation.

Transcript

Can you discuss the design and the objectives of the phase 2 CAPTIVATE study?

CAPTIVATE was a study that began several years ago. It was a phase 2 study with an interest in exploring the efficacy and safety of putting the 2 most commonly used targeted treatments with small molecule inhibitors together, and that would be ibrutinib and venetoclax. At the time, ibrutinib was the only BTK [Bruton tyrosine kinase] inhibitor available. Of course, now there are additional BTK inhibitors. Venetoclax remains the only BCL2 inhibitor.

We have been using BTK inhibitors a lot in treating CLL patients. They are wonderful in how effective they are. There’s a presentation at this meeting of using a BTK inhibitor as a first-line treatment with ibrutinib, the RESONATE-2 10-plus year follow-up. The majority of patients still have not progressed even 10 years in, so this is an incredibly effective way to treat CLL patients. But with the indefinite treatment is a potential for toxicity. We are becoming more informed on ibrutinib’s toxicities specifically. And then there’s obviously the financial toxicity of having to take a treatment for years.

So, this study [CAPTIVATE] was interested in harnessing the deep responses seen by venetoclax and still involving BTK inhibition and its positive, long-term effects on controlling CLL using the 2 agents together in an all-oral combination that’s given over a defined treatment timeline over the course of 1 year after a 3-month single-agent ibrutinib lead-in.