The last decade has seen much needed progress in the development of novel therapies against Mantle cell lymphoma (MCL). The licensing of the Bruton’s tyrosine kinase inhibitor (BTKi) Ibrutinib for relapsed/refractory MCL was a significant therapeutic milestone in the management of this condition and represents a highly effective, novel oral therapy in a disease characterised by progressive development of chemo-resistance. However, patients invariably progress on Ibrutinib. Multiple studies have demonstrated limited efficacy of subsequent therapies and poor outcomes post-Ibrutinib. In addition, patients with MCL displaying high-risk features such as blastoid morphology and/or TP53 mutations, are now widely recognised as a subset that are particularly challenging to manage. Brexucabtagene-autoleucel (Brexu-Cel) is a novel chimeric antigen receptor (CAR) T-cell therapy that was recently approved for management of patients relapsing on Ibrutinib. This approval was based on the ZUMA-2 study, which demonstrated impressive activity of Brexu-Cel in relapsed/refractory MCL, including in patients with high-risk features. Brexu-Cel is however not without toxicity and is associated with a moderate incidence of severe cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Importantly these adverse events are both manageable and acceptable for a therapy that holds the promise of providing long-term remissions from MCL. This review examines CAR-T therapy in MCL including the implementation of Brexu-Cel therapy in the routine management of MCL, and discusses some of the other novel cellular therapy approaches currently being evaluated in this disease.
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