Unmet needs in relapsed/refractory mantle cell lymphoma (r/r MCL) post-covalent Bruton tyrosine kinase inhibitor (BTKi): a systematic literature review and meta-analysis

To quantify the clinical unmet need of r/r MCL patients who progress on a covalent Bruton tyrosine kinase inhibitor (BTKi), we conducted a systematic review to identify studies that reported overall survival (OS), progression-free survival (PFS), or response outcomes of patients who received a chemo(immunotherapy) ± targeted agent standard therapy (STx) or brexucabtagene autoleucel (brexu-cel) in the post-BTKi setting. Twenty-six studies (23 observational; three trials) reporting outcomes from 2005 to 2022 were included. Using two-stage frequentist meta-analyses, the estimated median PFS/OS for patients treated with an STx was 7.6 months (95% CI: 3.9-14.6) and 9.1 months (95% CI: 7.3-11.3), respectively. The estimated objective response rate (ORR) was 45% (95% CI: 34-57%). For patients treated with brexu-cel, the estimated median PFS/OS was 14.9 months (95% CI: 10.5-21.0) and 32.1 months (95% CI: 25.2-41.2), with a pooled ORR of 89% (95% CI: 86-91%). Our findings highlight a significant unmet need for patients whose disease progresses on a covalent BTKi.