Ibrutinib plus venetoclax produced a complete response and complete response with incomplete bone marrow recovery rate of 56% in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma.
Ibrutinib (Imbruvica) plus venetoclax (Venclexta) produced a complete response (CR) and complete response with incomplete bone marrow recovery (CRi) rate of 56% in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), according to data presented at the 2021 ASCO Annual Meeting.
The phase 2 CAPTIVATE study (NCT02910583) found similarly high rates of overall survival (OS) and progression-free survival (PFS) with the combination therapy for patients overall and with high-risk features.
“The primary end point was met, with a complete response rate of 56% in patients without deletion(17p),” lead author Paolo Ghia, MD, PhD, of the Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele in Milan, Italy, explained in his presentation of the data. “The complete response [rate] was 55% in the all-treated population, and the overall response rate was 96%.”
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.
Of the 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%).
Further, for 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) treated with the combination had a 96% PFS rate (95% CI, 91%-98%). 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%). Twenty-three percent of patients experienced serious AEs, with only 1 fatal AE observed.
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.
“All of these results together support the idea of the combination of ibrutinib plus venetoclax as an all-oral, once daily, chemo[therapy]-free, fixed-duration [treatment] that may achieve deep responses and undetectable MRD in a vast majority of patients,” concluded Ghia in his presentation of the data.
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.