Effective Tumor Debulking with Ibrutinib Before Initiation of Venetoclax: Results from the CAPTIVATE Minimal Residual Disease and Fixed-Duration Cohorts
- Author(s)
- Barr, PM; Tedeschi, A; Wierda, WG; Allan, JN; Ghia, P; Vallisa, D; Jacobs, R; O'Brien, S; Grigg, AP; Walker, P; Zhou, C; Ninomoto, J; Krigsfeld, G; Tam, CS;
- Details
- Publication Year 2022-10-14,Volume 28,Issue #20,Page 4385-4391
- Journal Title
- Clinical Cancer Research
- Publication Type
- Research article
- Abstract
- PURPOSE: The phase II CAPTIVATE study investigated first-line treatment with ibrutinib plus venetoclax for chronic lymphocytic leukemia in two cohorts: minimal residual disease (MRD)-guided randomized treatment discontinuation (MRD cohort) and fixed duration (FD cohort). We report tumor debulking and tumor lysis syndrome (TLS) risk category reduction with three cycles of single-agent ibrutinib lead-in before initiation of venetoclax using pooled data from the MRD and FD cohorts. PATIENTS AND METHODS: In both cohorts, patients initially received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day). RESULTS: In the total population (N = 323), the following decreases from baseline to after ibrutinib lead-in were observed: percentage of patients with a lymph node diameter >/=5 cm decreased from 31% to 4%, with absolute lymphocyte count >/=25 x 109/L from 76% to 65%, with high tumor burden category for TLS risk from 23% to 2%, and with an indication for hospitalization (high TLS risk, or medium TLS risk and creatinine clearance <80 mL/minute) from 43% to 18%. Laboratory TLS per Howard criteria occurred in one patient; no clinical TLS was observed. CONCLUSIONS: Three cycles of ibrutinib lead-in before venetoclax initiation provides effective tumor debulking, decreases the TLS risk category and reduces the need for hospitalization for intensive monitoring for TLS.
- Keywords
- Adenine/analogs & derivatives; Antineoplastic Combined Chemotherapy Protocols/adverse effects; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use; Creatinine/therapeutic use; Cytoreduction Surgical Procedures; Humans; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/pathology; Neoplasm, Residual/drug therapy; Piperidines; Sulfonamides; *Tumor Lysis Syndrome/drug therapy/etiology
- Department(s)
- Clinical Haematology
- PubMed ID
- 35939599
- Publisher's Version
- https://doi.org/10.1158/1078-0432.CCR-22-0504
- Open Access at Publisher's Site
https://doi.org/10.1158/1078-0432.Ccr-22-0504- Terms of Use/Rights Notice
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Creation Date: 2024-09-26 05:45:32
Last Modified: 2024-09-26 05:48:04