T-Cell Fitness and Treatment Sequencing in Multiple Myeloma

In this segment, Dr. Joseph Mikhael and Dr. Scott Goldsmith discuss how T-cell fitness may influence treatment sequencing in multiple myeloma, particularly as chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies become increasingly important treatment options. Dr. Goldsmith explains that prior therapies, including transplant conditioning regimens, alkylating agents, proteasome inhibitors, and corticosteroids, may affect T-cell function. However, the extent and duration of these effects, as well as their implications for subsequent treatment outcomes, remain incompletely understood. The discussion explores the biological rationale for investigating cereblon E3 ligase modulators (CELMoDs) as potential treatment partners for T-cell-redirecting therapies. Dr. Goldsmith outlines several areas of investigation, including CELMoD use before leukapheresis, during the bridging period before CAR T-cell infusion, following CAR T-cell therapy to potentially support persistence, and in combination with bispecific antibodies. The segment highlights emerging translational evidence supporting these approaches while emphasizing the need for further clinical studies to determine optimal sequencing strategies and establish whether these potential immune effects translate into improved outcomes for patients with multiple myeloma.