Mantle cell lymphoma outcomes following sequential first-line bendamustine-rituximab and second-line Bruton’s tyrosine kinase inhibitor therapy

Addition of Bruton's tyrosine kinase inhibitor (BTKi) to first-line (1 L) bendamustine-rituximab (BR) improved progression-free survival (PFS) in patients with mantle cell lymphoma (MCL) in the SHINE and ECHO trials. We investigated whether sequential treatment with 1 L BR and second-line (2 L) BTKi can result in similar cumulative PFS compared to BR-BTKi combination therapy, using a multicenter cohort of 755 patients treated with 1 L BR between 2014 and 2020. Event-free survival (EFS), EFS2, and overall survival (OS) were analyzed. By intention-to-treat (ITT), EFS2 was defined as time from 1 L BR start to progression/relapse or retreatment following 2 L BTKi or death. After a median follow-up of 61.4 (95% CI 56.4-65.9) months, the median EFS after 1 L BR was 34.2 (95% CI 31.5-38.4) months. The median EFS2 following 1 L BR and 2 L BTKi by ITT analysis was 64.8 (95% CI 56.7-82.8) months, and the 5-year OS rate after 1 L BR was 57.9% (95% CI 54.1-62.0%), close to SHINE and ECHO results. Patients without high-risk features (high simplified MIPI, high Ki-67, blastoid/pleomorphic morphology, TP53 mutation, or complex karyotype) had more favorable survival outcomes. These results suggest that sequential treatment with 1 L BR and 2 L BTKi remains reasonable for select patients with MCL, particularly those without high-risk features.