Venetoclax Combination Shows Promise in Chronic Lymphocytic Leukemia

The combination of ibrutinib (Imbruvica) plus venetoclax (Venclexta) produced a complete response (CR) and complete response with incomplete bone marrow recovery (CRi) rate of 56% among patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), according to a presentation at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Conference.

Results of the phase 2 CAPTIVATE study showed similar rates of overall survival (OS) and progression-free survival (PFS) with the combination therapy for patients with high-risk features.

"We are encouraged by these promising results, which indicate ibrutinib and venetoclax combined has the potential to serve as an important chemotherapy-free, fixed-duration treatment option for people living with CLL," said Dr. Paolo Ghia, MD, PhD, professor of Medical Oncology at the Università Vita-Salute San Raffaele and CAPTIVATE steering committee member and investigator, in a press release

The primary analysis focused on the fixed-duration cohort of the CAPTIVATE study, with patients receiving 3 cycles of ibrutinib followed by 12 cycles of ibrutinib plus venetoclax. A total of 159 previously untreated patients with CLL/SLL, aged 70 years or younger, with an ECOG performance score of 2 or less were enrolled in the trial.

Among 159 patients enrolled, 147 (92%) completed the 12 cycles of ibrutinib plus venetoclax. The median time on study was 27.9 months (range, 0.8-33.2) with a median treatment duration of 13.8 months (range, 0.5-24.9). The median follow-up was 14.0 months after treatment completion

In patients without del(17p), the CR rate was 56% (95% CI, 48%-64%) with the all-treated population reporting a 55% CR rate. The only exception was observed in the bulky disease category, where patients with bulky disease had a CR rate of 31% (95% CI, 18%-44%).

Among patients with bone marrow or peripheral disease, high rates of undetectable minimal residual disease (uMRD) were observed, including in patients with high-risk disease features.

When examining patients at 24 months, those without del(17p) had a 96% PFS rate (95% CI, 91%-98%) with the combination. For OS, the 24-month rate was 98% (95% CI, 94%-99%) for this patient cohort. The median follow-up time was 27.9 months (range, 0.8-33.2).

The most common any-grade adverse effects (AEs) for the combination treatment were diarrhea (62%), nausea (43%), neutropenia (42%), and arthralgia (33%). Grade 3 or 4 AEs included neutropenia (33%), infections (8%), hypertension (6%), and neutrophil count decrease (5%), and 23% of patients experienced serious AEs, with 1 fatal AE.

The primary end point of the research was investigator-assessed CR/CRi for patients without del(17p), with key secondary end points focusing on overall response rate, duration of response, uMRD rates, progression-free survival, overall survival, tumor lysis syndrome reduction, and safety.

"Combining our novel therapies to deliver a new potential treatment is an example of AbbVie's innovative approach to identify options for difficult-to-treat blood cancers, like CLL," said Mohamed Zaki, MD, PhD, vice president and global head of oncology development, AbbVie, said in a press release. "We are proud to be leading in the development of this combination to continue raising the standards of care for the blood cancer community."

This combination therapy is currently being examined in a complementary older population for the randomized phase 3 GLOW study (NCT03462719), results of which are expected soon.

Reference

CAPTIVATE Study Shows an IMBRUVICA® (ibrutinib) Plus VENCLEXTA®/VENCLYXTO® (venetoclax) Chemotherapy-Free Combination Has Potential to Provide Remission After Fixed-Duration Treatment for Chronic Lymphocytic Leukemia (CLL) [news release]. AbbVie. June 7, 2021. Accessed June 7, 2021.