Outcomes in Patients with High-Risk Features after Fixed-Duration Ibrutinib plus Venetoclax: Phase II CAPTIVATE Study in First-Line Chronic Lymphocytic Leukemia
Year: 2023
Type: article
Abstract: PURPOSE: The CAPTIVATE study investigated first-line ibrutinib plus venetoclax for chronic lymphocytic leukemia in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). We report outcomes of fixed-duration ibrutinib plus venetoclax in patients with high-risk genomic features [del(17p), TP53 mutation, and/or unmutated immunoglobulin heavy chain (IGHV)] in CAPTIVATE. PATIENTS AND METHODS: Patients received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day). FD cohort patients (n = 159) received no further treatment. Forty-three MRD cohort patients with confirmed undetectable MRD (uMRD) after 12 cycles of ibrutinib plus venetoclax received randomized placebo treatment. RESULTS: Of 195 patients with known status of genomic risk features at baseline, 129 (66%) had ≥1 high-risk feature. Overall response rates were >95% regardless of high-risk features. In patients with and without high-risk features, respectively, complete response (CR) rates were 61% and 53%; best uMRD rates: 88% and 70% (peripheral blood) and 72% and 61% (bone marrow); 36-month progression-free survival (PFS) rates: 88% and 92%. In subsets with del(17p)/TP53 mutation (n = 29) and unmutated IGHV without del(17p)/TP53 mutation (n = 100), respectively, CR rates were 52% and 64%; uMRD rates: 83% and 90% (peripheral blood) and 45% and 80% (bone marrow); 36-month PFS rates: 81% and 90%. Thirty-six-month overall survival (OS) rates were >95% regardless of high-risk features. CONCLUSIONS: Deep, durable responses and sustained PFS seen with fixed-duration ibrutinib plus venetoclax are maintained in patients with high-risk genomic features, with similar PFS and OS to those without high-risk features. See related commentary by Rogers, p. 2561.
Source: Clinical Cancer Research
Institutions: Weill Cornell Medicine, Sarah Cannon, Tennessee Oncology, City Of Hope National Medical Center, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, The University of Melbourne, Peter MacCallum Cancer Centre, St Vincent's Hospital Melbourne, University of California San Diego, Moores Cancer Center, University of Rochester Medicine, North Shore Hospital, Waitemata District Health Board, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Levine Cancer Institute, Flinders University, Flinders Medical Centre, University of Padua, AbbVie (United States), The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funder: Pharmacyclics
OpenAlex ID: W4379598412