Cereblon-Targeting Ligase Degraders in Myeloma Mechanisms of Action and Resistance

CRBN-dependent degraders represent a remarkable class of drugs with a pleotropic mechanisms of action with direct anti -MM as well as immunomodulatory effects. Defining the mechanisms of action and resistance to these molecules allowed the development of next -generation CRBN-dependent degraders (iberdomide, mezigdomide, CFT7455) with enhanced activity and potency compared with first -generation IMiDs. Ongoing explorations of these molecules and the combination of CRBNdependent degraders with other novel anti-myeloma therapeutics with further unravel the pandora box effects of this class of drugs.