Immune Effects and Clinical Translation of CELMoDs in Multiple Myeloma

The discussion turns to the immunomodulatory effects of CELMoDs in multiple myeloma, with Dr. Goldsmith describing preclinical evidence suggesting that CELMoDs can enhance T-cell and NK-cell activity through effects on cytokine signaling and immune-mediated mechanisms. The panel also discusses neutropenia as an important on-target adverse effect associated with cereblon-mediated degradation of Ikaros and Aiolos, which have roles in neutrophil maturation. Dr. Richardson highlights the potential for CELMoDs to complement other treatment approaches by engaging both tumor-cell biology and the immune system, while also describing clinical observations linking the pharmacodynamic effects seen in laboratory studies with changes observed in patients. The conversation then connects these findings with activity observed in heavily pretreated multiple myeloma, including patients previously exposed to IMiD-based therapy. Dr. Mikhael summarizes how the mechanistic rationale has supported continued clinical development of iberdomide and mezigdomide, setting the stage for discussion of emerging clinical data, including the SUCCESSOR-2 study.