Dr. Jacobs on the Continued Impact of the CAPTIVATE trial in CLL

Ryan Jacobs, MD, hematologist and medical oncologist, Levine Cancer Institute, Atrium Health, discusses the implications of next-line treatment strategies following long-term data of the phase 2 CAPTIVATE trial (NCT02910583) in chronic lymphocytic leukemia (CLL).

The multi-cohort trial investigated the impact of fixed-duration ibrutinib (Imbruvia) plus venetoclax (Venclexta) on both minimal residual disease (MRD)-guided discontinuation and treatment outcomes in patients with treatment-naïve CLL. A 5-year follow-up analysis was conducted to assess the efficacy and safety of this combination regimen in patients with confirmed MRD. Of the original 164 patients in the MRD cohort, 86 achieved MRD negativity in both peripheral blood and bone marrow. These patients were then randomly assigned to receive either a fixed-duration placebo regimen or ibrutinib monotherapy.

At the time of follow-up, 95% of patients who continued with single-agent ibrutinib remained progression-free, Jacobs states. Patients receiving placebo achieved a progression-free survival (PFS) rate of 88% without additional treatment. However, the difference between PFS rates is not yet statistically significant. Moreover, no significant atrial fibrillation events, which are commonly associated with ibrutinib, occurred in the placebo group after randomization, he notes.

The results associated with these follow-up data indicate that the administration of ibrutinib and venetoclax as a first-line treatment not only led to deep and durable clinical responses, but may also allow patients to safely discontinue treatment while remaining disease free, Jacobs states.

Treatment discontinuation has several advantages, including a reduction in long-term drug-related toxicities and an improvement in quality of life (QOL), Jacobs continues. QOL benefit specifically includes both mental and financial wellness, as many patients struggle to afford maintenance therapies in accordance with the current recommendations, he concludes.