CELMoDs With CAR T-Cell Therapy and Bispecific Antibodies in Multiple Myeloma

In this segment, Dr. Joseph Mikhael and Dr. Scott Goldsmith discuss the potential role of cereblon E3 ligase modulators (CELMoDs) following chimeric antigen receptor (CAR) T-cell therapy and in combination with bispecific antibodies for multiple myeloma. Dr. Goldsmith reviews preclinical and translational findings suggesting that mezigdomide may reduce T-cell exhaustion, enhance T-cell activation, and support CAR T-cell persistence. Experimental findings, including increased CAR T-cell persistence in vitro and prolonged survival in mouse models, provide a rationale for further investigation, but their clinical relevance remains to be established. The experts consider whether CELMoDs could eventually be used as maintenance therapy after CAR T-cell infusion to sustain treatment activity. They also explore the potential for combining CELMoDs with bispecific antibodies, particularly in patients with challenging disease features such as extramedullary involvement. The discussion highlights the possibility that CELMoDs could complement immune-based therapies through their direct antimyeloma activity and effects on immune function. However, Dr. Mikhael and Dr. Goldsmith emphasize the need for additional translational research and clinical trials to determine the safety, efficacy, and optimal use of these strategies in multiple myeloma.