Safety and Efficacy of Ibrutinib in Combination With Rituximab and Lenalidomide in Previously Untreated Follicular and Marginal Zone Lymphoma: An Open Label, Phase 2 Study

Authors

Max J Gordon
Lei Feng
Paolo Strati
Hun Ju Lee
Fredrick B Hagemeister
Jason R Westin
Felipe Samaniego
Mario L Marques-Piubelli
Francisco Vega Vazquez
Edwin R Parra Cuentas
Luisa M Solis-Soto
Wencai Ma
Jing Wang
Linda Claret
Barbara Averill
Karina Ibanez
Luis E Fayad
Christopher R Flowers
Michael R Green
R Eric Davis
Sattva S Neelapu
Nathan H Fowler
Loretta J Nastoupil

Publication Date

3-15-2024

Journal

Cancer

Abstract

Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity-rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study.

Methods: The authors conducted an open-label, phase 2 clinical trial of IRR for previously untreated FL and MZL. The primary end point was progression-free survival (PFS) at 24 months.

Results: This study included 48 participants with previously untreated FL grade 1-3a (N = 38), or MZL (N = 10). Participants received 12, 28-day cycles of lenalidomide (15 mg, days 1-21 cycle 1; 20 mg, cycles 2-12), rituximab (375 mg/m2 weekly in cycle 1; day 1 cycles 2-12), and ibrutinib 560 mg daily. With a median follow-up of 65.3 months, the estimated PFS at 24 months was 78.8% (95% confidence interval [CI], 68.0%-91.4%) and 60-month PFS was 59.7% (95% CI, 46.6%-76.4%). One death occurred unrelated to disease progression. Grade 3-4 adverse events were observed in 64.6%, including 50% with grade 3-4 rash.

Conclusions: IRR is highly active as frontline therapy for FL and MZL. Compared to historical results with lenalidomide and rituximab, PFS is similar with higher grade 3-4 toxicity, particularly rash. The study was registered with ClinicalTrials.gov (NCT02532257).

Keywords

Humans, Rituximab, Lenalidomide, Antineoplastic Combined Chemotherapy Protocols, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Exanthema, Adenine, Piperidines, Non-Hodgkin lymphoma (NHL), indolent lymphoma, targeted therapy

DOI

10.1002/cncr.35114

PMID

37985359

PMCID

PMC10922670

PubMedCentral® Posted Date

3-15-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes