In vivo CAR T-cell therapy: determinants of response and durability

In vivo chimeric antigen receptor (CAR) T-cell therapy generates engineered lymphocytes inside the patient, bypassing leukapheresis, ex vivo manufacturing and, in many programs, lymphodepletion. Studies in relapsed or refractory multiple myeloma report deep responses with measurable residual disease negativity after B-cell maturation antigen-directed treatment. Because the administered product is a delivery system, cells are shaped by the host environment, which may complicate interpretation of efficacy and safety. This Review summarizes clinical data and defines determinants of response that could be optimized for durable translation. It focuses on multiple myeloma, where clinical experience is most mature, while drawing on autoimmune applications.