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Ibrutinib Maintenance Following Induction for Untreated MCL: Initial Safety Report

There is evidence to support rituximab maintenance therapy in patients with previously untreated mantle-cell lymphoma (MCL) who undergo induction chemoimmunotherapy followed by autologous stem cell transplant (ASCT). However, although maintenance rituximab has improved progression-free survival (PFS) and overall survival (OS) in this population, the optimal approach for maintenance therapy has not yet been defined.1

Ibrutinib, a selective Bruton’s tyrosine kinase inhibitor, is approved for the treatment of relapsed or refractory MCL. To date, ibrutinib maintenance following induction for patients with treatment-naïve MCL has not been explored. Here, researchers reported the preliminary results of a multicenter phase 2 trial assessing the efficacy and safety of ibrutinib maintenance for MCL after frontline induction.

The study evaluated patients with MCL in complete response (CR) or partial response (PR) to frontline chemoimmunotherapy with or without ASCT. Patients received a daily maintenance dose of 560 mg of ibrutinib for up to 4 years. The primary study objective was 3-year PFS rate, and secondary objectives were PR to CR conversions, median OS of 4 years, and toxicity, with minimal residual disease (MRD) assessments planned as an exploratory end point.

A total of 36 patients with a median age of 60 years were enrolled. Twenty-eight patients had advanced- stage disease and 9 had extranodal disease. Using the Mantle Cell Lymphoma International Prognostic Index, 18 (50%), 7 (19%), and 11 (31%) patients were categorized with low- versus intermediate- versus high-risk disease, respectively. For induction, 17 (47%) patients received bendamustine plus rituximab, 18 (50%) received a cytarabine-based regimen, and 1 received (3%) R-CHOP. Half (N = 18) of enrolled patients received ASCT consolidation prior to enrollment. Thirty-three (92%) patients achieved CR and 3 (8%) achieved PR with induction therapy; there was 1 PR to CR conversion on ibrutinib maintenance.

At a median follow-up of 19 months, two-thirds (24/36) of the patients remained on ibrutinib maintenance (median, 16.5 cycles; range, 1-49). The most commonly reported grade ≥3 treatment-related adverse events were lymphopenia (19%), neutropenia (12%), leukopenia (8%), hypertension (3%), and bleeding (3%). Treatment-related adverse events led to dose reductions or interruptions in 25 (69%) patients, including permanent dose reductions in 7 (19%), and treatment discontinuation in 9 (25%).

This study demonstrates that ibrutinib maintenance is feasible in patients with MCL who respond to front-line chemoimmunotherapy with or without ASCT with manageable toxicities consistent with prior reports of ibrutinib. In follow-up analyses, the researchers will evaluate MRD status correlations with PFS and OS, which is expected to provide further insight on clinical relevance for this approach.

Abstract 7542; Karmali R, et al.

Reference

  1. Hilal T, Wang Z, Almader-Douglas D, et al. Rituximab maintenance therapy for mantle cell lymphoma: a systematic review and meta-analysis. Am J Hematol. 2018;93:1220-1226.
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Last modified: August 30, 2021