Venetoclax and ibrutinib induces durable clinical responses in marginal zone lymphoma
- Author(s)
- Handunnetti, SM; Khot, A; Blombery, P; Burbury, K; Thompson, PA; Ritchie, D; Hicks, RJ; Burke, G; Koldej, RM; Bressel, M; Di Iulio, JL; Westerman, DA; Lade, S; Roberts, AW; Seymour, JF; Tam, CS; Anderson, MA;
- Journal Title
- Blood Advances
- Publication Type
- Dec 11
- Abstract
- Oral ibrutinib (I) and venetoclax (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 560mg daily, after 4 weeks venetoclax commenced with weekly dose escalation to 400mg 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). 15 patients with MZL were treated, 14 are included in efficacy analysis and 15 evaluable for safety. Overall response was 79% (95% CI 49-95) by FDG PET (43% (95% CI 18-71) CR rate). By CT 16-week CR rate was 29% (95% CI 8-58). Best response within 56 weeks was 57% (95% CI 37-80) CR, which is higher than historic ibrutinib monotherapy control (3% CR) (p < 0.001). MRD clearance at week 56 was 40%. Six MRD negative CR patients entered ETI with 4 remaining disease-free at median 4 years. With median follow up 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. Trial registered at www.clinicaltrials.gov as NCT02471391.
- Publisher
- ASH
- Research Division(s)
- Blood Cells and Blood Cancer
- PubMed ID
- 41380113
- Publisher's Version
- https://doi.org/10.1182/bloodadvances.2025016646
- Open Access at Publisher's Site
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Creation Date: 2025-12-15 09:44:04
Last Modified: 2025-12-15 09:44:10