First-line treatment with ibrutinib plus venetoclax has been shown to confer high rates of undetectable minimal residual disease (uMRD) in peripheral blood and bone marrow in patients with chronic lymphocytic leukemia (CLL).1 The ongoing CAPTIVATE study evaluates whether time-limited treatment with ibrutinib plus venetoclax will allow for treatment-free remission in patients with CLL. Researchers presented primary results from the trial evaluating whether treatment with ibrutinib plus venetoclax allows for treatment-free remission for patients with uMRD.
The multicenter phase 2 CAPTIVATE study enrolls patients with previously untreated CLL/small lymphocytic lymphoma (SLL) into 2 cohorts: minimal residual disease (MRD) and fixed duration. Patients in both cohorts receive ibrutinib for 3 cycles followed by combination treatment with ibrutinib plus venetoclax for at least 12 cycles. Patients in the MRD cohort are then randomized by MRD status to receive placebo or further treatment.
Following the initial treatment with 3 cycles of ibrutinib and 12 cycles of ibrutinib plus venetoclax, patients with confirmed uMRD are randomized to receive placebo or ibrutinib. Patients who do not meet criteria for uMRD are randomized to receive open-label treatment with ibrutinib or continued combination therapy with ibrutinib and venetoclax.
A total of 164 patients were enrolled in the MRD cohort, with a median age of 58 years.2 High-risk features of enrolled patients included 17p deletion (16%), 11q deletion (17%), and TP53 mutation (20%). Complex karyotype was present in 19% of patients and unmutated IGHV in 60%.
Of the 164 patients enrolled in the MRD cohort, 149 completed the prerandomization treatment of 3 cycles of ibrutinib lead-in followed by 12 cycles of combined ibrutinib plus venetoclax. Of the patients randomized, 86 (58%) had confirmed uMRD in peripheral blood and bone marrow. In the confirmed uMRD group, the 1-year disease-free survival rate was not significantly different for patients randomized to placebo (95%) versus ibrutinib (100%).
Confirmed uMRD was not achieved in 63 (42%) randomized patients. For patients receiving ibrutinib, uMRD rates improved from 32% to 42% in the bone marrow and remained at 45% in the peripheral blood. For patients receiving ibrutinib plus venetoclax, uMRD rates improved from 31% to 66% in the bone marrow and 50% to 69% in the peripheral blood. In all groups, 30-month progression-free survival rates were greater than 95%.
Adverse events were primarily grade 1/2. These mostly occurred in early cycles of treatment with ibrutinib plus venetoclax. Only modest differences were noted between randomized treatment groups. The safety profile of ibrutinib plus venetoclax was consistent with known adverse events for ibrutinib and venetoclax, and no new safety signals were observed.
Following treatment with ibrutinib plus venetoclax, patients receiving placebo and those continuing ibrutinib had similar 1-year disease-free survival rates. In addition, the 30-month progression-free survival rate was 95% or greater across all treatment arms. Researchers concluded that these findings support a fixed-duration treatment that can offer treatment-free remission for patients with CLL/SLL.
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