Understanding and addressing resistance to IMiDs immunomodulatory compounds in multiple myeloma

IMiDs are fundamental multiple myeloma treatments, though therapeutic resistance inevitably develops, posing a major clinical challenge. This review examines diverse resistance mechanisms, specifically cereblon-dependent genetic mutations, epigenetic silencing, and immune microenvironment dysregulation. It details strategies to overcome these hurdles, highlighting potent next-generation CELMoDs and novel combination therapies involving immunotherapies and epigenetic resensitizers to enhance patient outcomes.