All-Oral, Chemo-Free Regimen Provides Durable Response in Frontline CLL Setting

Three-year follow-up data from the phase II CAPTIVATE trial showed clinically meaningful progression-free survival (PFS) in patients with chronic lymphocytic leukemia (CLL) receiving frontline fixed-duration ibrutinib plus venetoclax. The results were presented at the 2022 ASCO Annual Meeting.

The multicenter, international study included 159 patients (median age, 60 years) aged ≤70 years with untreated CLL/small lymphocytic leukemia (SLL) who received first-line treatment with three cycles of ibrutinib followed by 12 cycles of ibrutinib 420 mg orally daily plus venetoclax 400 mg orally daily.

Among the cohort, 17% of patients had del(17p)/TP53 mutations, 56% had unmutated immunoglobulin heavy chain gene (IGHV), and 19% had complex karyotype. Most patients (n=147; 92%) completed treatment with ibrutinib and venetoclax.

Primary analysis data were previously reported, and after another year of follow-up (median time on study, 39 months; range, 1-41 months), the overall response rate (ORR) was 96%. The ORR was consistent regardless of high-risk patient features: 96% in patients with del(17p)/TP53 mutations and 97% in patients with unmutated IGHV. Overall, 57% experienced a complete response (CR; primary endpoint). Among those in CR, 93% experienced durable responses extending more than 12 months post-treatment. The 36-month PFS and overall survival were 88 months and 98 months, respectively.

A total of 85 patients had undetectable minimal residual disease (MRD) in peripheral blood three months after treatment, and of those patients, 78% (n=66) maintained undetectable MRD through 12 months post-treatment.

No new safety signals were observed since the primary analysis. Adverse events occurring in more than 30% of patients included arthralgia, diarrhea, nausea, and neutropenia. Median time to onset of common adverse events was four months, and median time to resolution or improvement ranged from 16.5 days to 42.5 days.

All patients are now off treatment. As of April 2022, 12 patients who progressed after fixed-duration treatment were retreated with single-agent ibrutinib following disease progression, with nine achieving partial response (PR), one achieving PR with lymphocytosis, and one achieving stable disease.

“Ibrutinib plus venetoclax represents an efficacious, all-oral, once-daily, chemotherapy-free, fixed-duration regimen for previously untreated patients with CLL/SLL,” the authors concluded.

The study was sponsored by Pharmacyclics LLS, an AbbVie Company.

Reference

Wierda WG, Barr PM, Siddiqi T, et al. Fixed-duration (FD) ibrutinib (I) + venetoclax (V) for first-line (1L) treatment (tx) of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Three-year follow-up from the FD cohort of the phase 2 CAPTIVATE study. Abstract #7519. Presented at the 2022 American Society of Clinical Oncology Annual Meeting, June 3-7, 2022.