In follow-up data from the phase II CAPTIVATE study, ibrutinib plus venetoclax demonstrated a “favorable benefit-risk profile” in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).
The study was presented at the 2022 American Society of Hematology (ASH) Annual Meeting and Exhibition by John N. Allan, MD, of Weill Cornell Medicine in New York and colleagues.
The CAPTIVATE study is an international, multicenter phase II study evaluating first-line ibrutinib plus venetoclax in patients with previously untreated CLL/SLL who have indication for treatment.
After completion of ibrutinib plus venetoclax, patients with confirmed undetectable minimal residual disease (uMRD) were randomized to receive placebo or continue ibrutinib.
In primary analysis results presented at the 2021 ASH Annual Meeting and Exhibition, disease-free survival (DFS) rates were similar in patients from these two arms (95% and 100%, respectively) two years after randomization.
The new efficacy and safety results (see TABLE 1) represented a median follow-up of 56 months (range, 25–68; median 41 months post randomization).
A total of 164 patients were enrolled to receive combined ibrutinib plus venetoclax treatment; after completion, 86 patients with confirmed uMRD were randomly assigned to the placebo arm or single-agent ibrutinib arm (n=43 each).
TABLE 1: CAPTIVATE Study Efficacy Outcomes
|Efficacy outcomes, % (95% CI)||All treated placebo (N=43)||All treated ibrutinib (N=43)||High-risk* placebo (N=6)||High-risk ibrutinib (N=20)|
|DFS (three-year)||85 (69-93)||93 (80-98)||100 (100-100)||95 (70-99)|
|Progression-Free Survival (four-year)||88 (74-95)||95 (82-99)||100 (100-100)||95 (70-99)|
|Overall survival (four-year)||100 (100-100)||98 (84-100)||100 (100-100)||100 (100-100)|
*“High-risk” includes patients with del(17p), TP53, or complex karyotype.
“Efficacy outcomes in high-risk subgroups were consistent with the total population although low sample size in the [placebo] arm limits interpretation,” the authors wrote. “Together with the safety data, these results demonstrate a favorable benefit-risk profile with fixed duration [ibrutinib plus venetoclax].”
Allan J, Siddiqi T, Kipps T, et al. Treatment outcomes after undetectable MRD with first-line ibrutinib (Ibr) plus venetoclax (Ven): fixed duration treatment (placebo) versus continued Ibr with up to 5 years median follow-up in the CAPTIVATE study. Abstract #92. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.