Management of aggressive lymphoma after CAR T-cell therapy failure

Several recent advances have affected the treatment landscape of diffuse large B-cell lymphoma. Chimeric antigen receptor (CAR) T-cell therapy has transformed the management of chemorefractory disease. Two randomized studies in early relapse disease have expanded the label to provide access to CAR T-cell therapy as early as second line for some patients. Despite the durable remissions that have been achieved, many patients will experience relapse. There is a growing population of patients previously treated with CAR T-cell therapy facing dismal outcomes. We review the prospective studies that inform treatment options in later lines and highlight the limited data examining outcomes with novel therapies after CAR T-cell failure. The treatment landscape is anticipated to continue to evolve with the emergence of bispecific antibodies that appear to be a promising approach, particularly after CAR T-cell therapy, although little is known about overlapping mechanisms of resistance. Enrichment for patients who have received prior CAR T-cell therapy on prospective trials is a critical unmet need to inform the preferred management for these high-risk patients.