Chimeric antigen receptor T-cell therapy in aggressive lymphomas

This review provides the latest update on chimeric antigen receptor (CAR) T-cell therapy in diffuse large B-cell lymphoma (DLBCL), as of April 2025, with a focus on specific patient populations, long-term toxicities, and the optimal sequencing of therapies, particularly in view of emerging treatments such as bispecific antibodies.

Currently, three autologous CAR T-cell therapies targeting CD19 (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) have been approved for third-line treatment of DLBCL, demonstrating durable complete remission rates of up to 40%. More recently, axicabtagene ciloleucel and lisocabtagene maraleucel have been approved for second-line therapy in refractory or early-relapsed DLBCL. Additionally, the emergence of CD20/CD3 bispecific antibodies has expanded therapeutic options for relapsed/refractory DLBCL, raising questions about the optimal sequencing of these therapies. Growing real-world evidence further supports the efficacy of CAR T-cell therapy in specific populations, including elderly patients, patients with transformed indolent B-cell non-Hodgkin lymphoma, and those with Richter's transformation. Finally, extended follow-up periods have allowed for a better characterization of the long-term toxicities associated with CAR T-cell therapy.

Recent data on CAR T-cell therapy in DLBCL provides valuable insights into its benefits for specific populations, the optimization of treatment sequencing, and the management of long-term toxicities.