EXCALIBER-RRMM: Iberdomide in Relapsed/Refractory Multiple Myeloma

Dr. Joshua Richter reviews the EXCALIBER-RRMM study evaluating iberdomide in combination with daratumumab and dexamethasone in patients with relapsed/refractory multiple myeloma. He discusses the mechanism of CELMoDs, including cereblon-mediated degradation of Ikaros and Aiolos, as well as their direct antimyeloma and immune-modulating effects. The panel reviews the study design, patient population, dosing, and use of MRD-negative complete response as the primary endpoint. The discussion highlights the higher rate of MRD-negative CR with iberdomide, daratumumab, and dexamethasone compared with daratumumab, bortezomib, and dexamethasone, while emphasizing the importance of interpreting MRD findings within the context of the study population and comparator. Faculty also discuss the relevance of the comparator in contemporary relapsed/refractory multiple myeloma practice. Safety considerations include neutropenia, infection risk, and thromboembolic events, with discussion of growth factor support, dose interruptions, and dose modifications as approaches to managing treatment-related toxicity.