Martina Canichella, Elisabetta Abruzzese, Mariagiovanna Cefalo, Valentina Gianfelici, Carla Mazzone, Gentiana Elena Trotta, Roberta Laureana, Luca Cupelli, Maria Ilaria Del Principe
Examines the biological mechanisms underlying post-CAR-T relapse in B-ALL, NHL, and MM and reviews current and emerging strategies to prevent and manage relapse. Discusses consolidation approaches such as allogeneic hematopoietic stem cell transplantation, maintenance with targeted agents, and CAR-T cell reinfusion for relapse prevention, and the use of novel therapeutic agents like bispecific antibodies for relapse management. Notes that current evidence for relapse prevention and management strategies remains largely preliminary and limited by the paucity of randomized prospective trials.
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM); however, a substantial proportion of patients eventually experience disease relapse despite an initial response. This review provides a brief overview of CAR-T cell therapy, including its manufacturing process and associated toxicities, before examining the biological mechanisms underlying post-CAR-T relapse in B-ALL, NHL-particularly large B-cell lymphoma (LBCL)-and MM. We critically review current and emerging strategies to prevent and manage relapse. Strategies for relapse prevention primarily include consolidation approaches, such as allogeneic hematopoietic stem cell transplantation (allo-HSCT), maintenance with targeted agents (e.g., tyrosine kinase inhibitors in Philadelphia chromosome-positive B-ALL), and CAR-T cell reinfusion, whereas relapse management is disease-specific and increasingly incorporates novel therapeutic agents, including bispecific antibodies (BsAbs) and other targeted therapies. However, current evidence remains largely preliminary and is limited by the paucity of randomized prospective trials.