T‐Cell–Redirecting Immunotherapies in Relapsed/Refractory Mantle Cell Lymphoma: Current Evidence, Sequencing, and Future Directions

Relapsed/refractory (R/R) mantle cell lymphoma (MCL) remains a therapeutic challenge, particularly in patients with high‐risk features or prior exposure to Bruton's tyrosine kinase inhibitors (BTKis). The advent of T‐cell–redirecting immunotherapies, including chimeric antigen receptor T‐cell (CAR‐T) therapy and bispecific antibodies (BsAbs), has transformed the treatment landscape. CAR‐T therapies, such as brexu‐cel and liso‐cel, induce high overall response rates and durable remissions, even in heavily pretreated or BTKi‐refractory patients. However, CAR‐T administration is limited by logistical constraints, the need for bridging therapy, and the risk of severe toxicities, including cytokine release syndrome (CRS) and immune effector cell‐associated neurotoxicity syndrome (ICANS). BsAbs, targeting CD20 and CD3, offer an off‐the‐shelf, repeatable immunotherapeutic option suitable for outpatient use, with generally manageable toxicities. Step‐up dosing, corticosteroids, and anti‐IL6 therapy mitigate CRS, while hematologic toxicity and infections require vigilant monitoring. Clinical data indicate that BsAbs are active in both CAR‐T–naïve and post‐CAR‐T settings, providing disease control in patients ineligible for immediate CAR‐T therapy. Emerging evidence supports rational sequencing and combinatorial strategies to optimize outcomes. BsAbs may be employed as a bridge to CAR‐T, or CAR‐T may be used to consolidate BsAb‐induced remissions. Combination regimens, including CAR‐T or BsAbs with BTK inhibitors or other targeted agents, are under investigation to enhance the depth and durability of response. In conclusion, CAR‐T and BsAbs are complementary modalities in R/R MCL. Individualized therapeutic sequencing and rational combinations, tailored to disease biology and patient characteristics, represent the next frontier for improving long‐term outcomes in this historically high‐risk population.