Venetoclax and ibrutinib induces durable clinical responses in marginal zone lymphoma
- Author(s)
- Handunnetti, SM; Koldej, R; Khot, A; Di Iulio, J; Blombery, P; Burbury, K; Thompson, PA; Ritchie, D; Hicks, RJ; Burke, G; Bressel, M; Westerman, DA; Lade, S; Roberts, AW; Seymour, JF; Tam, CS; Anderson, MA;
- Details
- Publication Year 2026-03-10,Volume 10,Issue #5,Page 1733-1742
- Journal Title
- Blood Advances
- Publication Type
- Research article
- Abstract
- Oral ibrutinib and venetoclax (I+V) demonstrate activity as monotherapy in marginal zone lymphoma (MZL), with low complete response (CR) rates. I+V has shown good clinical activity with acceptable tolerability in other malignancies. We conducted a single-site, phase 2 trial of daily I+V in patients with MZL. Ibrutinib commenced at 560 mg daily; after 4 weeks, venetoclax commenced with weekly dose escalation to 400 mg daily. Combination therapy continued until disease progression or toxicity. The primary end point was week 16 CR. Minimal residual disease (MRD) was assessed by flow cytometry in bone marrow and peripheral blood. Patients achieving eradication of MRD could enter elective treatment interruption (ETI). Fifteen patients with MZL were treated; 14 are included in efficacy analysis, and 15 were evaluable for safety. Overall response was 79% (95% confidence interval [CI], 49-95) by F-fluorodeoxyglucose-positron-emission tomography (CR rate, 43%; 95% CI, 18-71). By computed tomography, 16-week CR rate was 29% (95% CI, 8-58). Best response within 56 weeks was 57% CR (95% CI, 37-80), which is higher than historic ibrutinib-monotherapy control (3% CR; P< .001). MRD clearance at week 56 was 40%. Six MRD-negative CR patients entered ETI, with 4 remaining disease-free at a median of 4 years. With a median follow-up of 5.5 years for the whole cohort, the 5-year progression-free survival estimate was 56% (95% CI, 27-78). I+V is safe and effective for MZL, with higher CR than with ibrutinib. Durable, ongoing CR was observed in MRD-negative patients. This trial was registered at www.clinicaltrials.gov as #NCT02471391.
- Publisher
- American Society of Hematology
- Department(s)
- Haematology; Pathology; Digital and Healthcare Innovation; Office of Cancer Research; Biostatistics and Clinical Trials
- Publisher's Version
- https://doi.org/10.1182/bloodadvances.2025016646
- Open Access at Publisher's Site
https://doi.org/10.1182/bloodadvances.2025016646- Terms of Use/Rights Notice
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Creation Date: 2026-01-20 05:38:39
Last Modified: 2026-03-10 04:07:01