CELMoDs After T-Cell–Engaging Therapy in Multiple Myeloma

The second clinical scenario considers a 72-year-old patient with multiple myeloma who is triple-class exposed and has experienced disease progression after a BCMA-directed T-cell-engaging therapy. Dr. Mikhael asks Dr. Goldsmith to discuss the rationale for investigating CELMoDs in this heavily pretreated setting, particularly when an oral treatment option is preferred. Dr. Goldsmith highlights the potential for CELMoDs to provide direct antimyeloma activity while also affecting immune-cell function, including in the context of prior T-cell-engaging therapies. The discussion then considers emerging clinical evidence for mezigdomide, including findings from the SUCCESSOR-2 study evaluating mezigdomide in combination with carfilzomib and dexamethasone. The panel also discusses how treatment intensity may be adapted according to disease burden, treatment goals, and tolerability, and notes the potential role of clinical trials investigating oral CELMoD-based approaches.