Fixed-Duration Ibrutinib, Venetoclax Oral Combination Effective in CLL/SLL

A fixed-duration regimen of first-line ibrutinib plus venetoclax provided deep, durable responses in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), according to results of the phase-2 CAPTIVATE study presented at the 2021 American Society of Clinical Oncology Annual Meeting.

Previous results from the measurable residual disease (MRD) cohort of the study showed that ibrutinib plus venetoclax resulted in undetectable MRD in two-thirds of patients treated with 12 cycles of the combination and a 30-month progression-free survival (PFS) rate of more than 95%.

Paolo Ghia, MD, PhD, professor of medical oncology at Vita-Salute San Raffaele University in Milan, Italy, presented results from the fixed-duration cohort that evaluated three cycles of ibrutinib followed by 12 cycles of ibrutinib plus venetoclax. This cohort included 159 patients with previously untreated CLL/SLL, including 17% of patients who had del17p/TP53 mutation.

“Though the use of continuous treatment with ibrutinib in CLL has been established as the standard of care for patients, including those with high-risk disease, fixed-duration therapy has been considered of interest to provide potential treatment-free periods, decreasing the time on the regimen and the possibility of adverse events and likely preventing the occurrence of resistance to therapy,” Dr. Ghia told ASH Clinical News.

The primary endpoint was the complete response (CR) rate, including CR with incomplete recovery. The median time on study was 27.9 months.

With this fixed-duration regimen, the CR rate was 55% in all patients. Of those who achieved CR, 89% had a durable response lasting one year or longer, the authors noted.

More than half of patients without del17p/TP53 mutation achieved CR (56%). In addition, the undetectable MRD rate in this group was 76% for peripheral blood and 62% for bone marrow.

Dr. Ghia also noted that undetectable MRD rates were similar between patients with and without bulky disease and were higher in patients with unmutated IGHV compared to those with mutated IGHV.

The overall response rate was 96% in the entire cohort.

“The positive results of the CAPTIVATE study underscore that ibrutinib in combination with venetoclax in an all-oral fixed duration delivers a high rate of progression-free survival at two years while enabling treatment-free remission for patients,” Dr. Ghia told ASH Clinical News.

The 24-month PFS rate was 95% in all patients and 96% in patients without del17p. The 24-month overall survival (OS) rate was 98% in both groups. In patients with del17p/TP53 mutations, the estimated 24- month PFS and OS were 84% and 96%, respectively.

Thirty-four patients were considered to be at high risk for tumor lysis syndrome at baseline. Of these, 94% shifted to medium or low risk after ibrutinib lead-in. No tumor lysis syndrome occurred.

The most common grade 3/4 adverse events (AEs) were neutropenia (33%), infection (8%), hypertension (6%), and neutropenia (5%). Eighty-eight percent of patients with AEs leading to dose reduction had resolution of events at the time of analysis, the authors reported.

Taken together, Dr. Ghia said that these results indicate that this “all-oral fixed duration combination may in the future become a possible new option for our patients to enable treatment-free durable remission.”

Study authors report relationships with Pharmacyclics and Janssen, which sponsored this study.


Ghia P, Allan JN, Siddiqi T, et al. Fixed-duration (FD) first-line treatment (tx) with ibrutinib (I) plus venetoclax (V) for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of the FD cohort of the phase 2 captivate study. Abstract #7501. Presented at the 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, 2021.