Outcomes in Patients with High-Risk Features after Fixed-Duration Ibrutinib plus Venetoclax: Phase II CAPTIVATE Study in First-Line Chronic Lymphocytic Leukemia
- Author(s)
- Allan, JN; Flinn, IW; Siddiqi, T; Ghia, P; Tam, CS; Kipps, TJ; Barr, PM; Elinder Camburn, A; Tedeschi, A; Badoux, XC; Jacobs, R; Kuss, BJ; Trentin, L; Zhou, C; Szoke, A; Abbazio, C; Wierda, WG;
- Details
- Publication Year 2023-07-14,Volume 29,Issue #14,Page 2593-2601
- Journal Title
- Clinical Cancer Research
- Publication Type
- Research 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.
- Publisher
- American Association for Cancer Research
- Keywords
- Humans; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/genetics/mortality; Piperidines/therapeutic use; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use
- Department(s)
- Clinical Haematology
- PubMed ID
- 37282671
- Publisher's Version
- https://doi.org/10.1158/1078-0432.CCR-22-2779
- Open Access at Publisher's Site
https://doi.org/10.1158/1078-0432.Ccr-22-2779- Terms of Use/Rights Notice
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Creation Date: 2023-10-17 06:55:46
Last Modified: 2023-10-17 06:58:32