CELMoDs as Holding and Bridging Therapy in Multiple Myeloma

In this segment, Dr. Joseph Mikhael and Dr. Scott Goldsmith explore the potential role of cereblon E3 ligase modulators (CELMoDs) as holding and bridging therapies for patients with multiple myeloma preparing for chimeric antigen receptor (CAR) T-cell therapy. Dr. Mikhael explains that holding therapy is administered before T-cell collection, whereas bridging therapy is given after leukapheresis while the CAR T-cell product is being manufactured. The discussion emphasizes the importance of controlling disease burden during this interval while avoiding treatments that could adversely affect T-cell function or compromise subsequent CAR T-cell therapy. Dr. Goldsmith highlights the potential value of therapies that not only reduce myeloma burden but may also support immune function, including T-cell and natural killer cell activity. The experts discuss how CELMoDs could be investigated before T-cell collection and during bridging therapy, particularly for patients who face delays in accessing specialized CAR T-cell centers. They also consider the importance of selecting treatments that preserve T-cell collection and manufacturing potential. Although these strategies offer a biological rationale for further investigation, clinical evidence is still needed to establish their effects on CAR T-cell manufacturing, safety, and patient outcomes.