Mezigdomide for multiple myeloma: a focus on phase 2 trial data

INTRODUCTION: The treatment armamentarium for multiple myeloma (MM) has evolved substantially over the past 20 years. Standard-of-care regimens for newly diagnosed MM and early relapsed/refractory disease (RRMM) include quadruplets and triplets comprising CD38 monoclonal antibodies, proteasome inhibitors, and/or immunomodulatory drugs, plus dexamethasone. Targeted agents and immune-based therapies are being used increasingly early in the treatment algorithm. There is an ongoing need for novel treatment options to improve outcomes with existing therapies and in subsequent lines of treatment. AREAS COVERED: We review preclinical/clinical data on the cereblon E3 ligase modulator mezigdomide, which is in phase 3 investigation in RRMM. We searched the published literature using PubMed, plus congress abstracts from the past 5 years and current records on ClinicalTrials.gov, using the terms 'mezigdomide' or 'CC-92480' and 'myeloma.' EXPERT OPINION: Mezigdomide, which is not currently approved for the treatment of MM, has higher cereblon binding affinity and greater potency for substrate protein degradation than the immunomodulatory drugs, and this is translating into notable clinical efficacy in early-phase trials, including in poor-prognosis settings such as triple-class-refractory disease. It has shown synergistic effects in preclinical studies with standard-of-care therapies and is being evaluated clinically in various combinations, including with/following T-cell engaging therapies for RRMM.