CELMoDs for Multiple Myeloma — Microlearning Activity 1 with Dr Paul G Richardson

·24 min·2 clips

Dr. Paul Richardson explains why CELMoDs are like 'CAR-T in a pill' for destroying multiple myeloma cells.

This episode is part one of a microlearning activity hosted by Dr. Neil Love, featuring Dr. Paul Richardson from Dana-Farber Cancer Institute. Dr. Richardson provides an overview of CELMoDs, specifically iberdomide and mezidamide, which modulate the cereblon E3 ligase complex to degrade proteins like Icaros and Aiolos. He describes mezidamide as closing the complex by 100%, compared to 15-20% for older drugs like lenalidomide. A patient case illustrates mezidamide's rapid effect, eliminating ALOS protein in a week. Clinical trial data shows mezidamide with dexamethasone achieved response rates above 40% in over 160 heavily pretreated patients, including 50% in BCMA-exposed patients and 30% in extramedullary disease. Iberdomide showed around 28% response rates. The drugs are being tested in combinations with agents like bortezomib, carfilzomib, and daratumumab, with response rates as high as 80%. Dr. Richardson discusses extramedullary disease, noting its prevalence and difficulty to treat, especially after immunotherapy failure. He highlights mezidamide's tissue penetration as key for targeting this. Central nervous system involvement is mentioned as a challenge, with drugs like pomalidomide and selinexor crossing the blood-brain barrier. Side effects include neutropenia and fatigue, but the drugs lack neuropathy, thromboembolism, and may have lower second cancer risks. Dr. Richardson expresses hope for FDA approval this year, emphasizing their community-based utility compared to hospital-dependent therapies like bispecifics and CAR-T.

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