Test your knowledge of mezigdomide in triple-class relapsed/refractory multiple myeloma

What is the primary mechanism by which mezigdomide (a CELMoD) exerts its anti-myeloma activity, and how does it differ from prior-generation IMiDs such as lenalidomide or pomalidomide?

Mezigdomide directly inhibits the proteasome to prevent degradation of pro-apoptotic proteins; IMiDs block VEGF-mediated angiogenesis in the bone marrow microenvironment

Mezigdomide binds cereblon with higher affinity than prior-generation IMiDs, achieving 100% closure of the CRL4 (CRBN) E3 ligase complex and resulting in superior degradation of Ikaros and Aiolos, while also retaining activity in IMiD-refractory disease

Mezigdomide acts as a monoclonal antibody targeting BCMA on the surface of plasma cells, triggering antibody-dependent cellular cytotoxicity

Mezigdomide functions as a selective BTK inhibitor that prevents B-cell receptor signaling in myeloma plasma cells, offering superior efficacy over IMiDs

Mr. R. develops grade 3 neutropenia (ANC 0.7 × 10⁹/L) at Day 14 of Cycle 1. What are the expected hematologic toxicities of mezigdomide-based therapy and the recommended management strategies?

Grade 3/4 neutropenia is rare (<10%) with MeziKd and typically resolves without intervention; routine G-CSF prophylaxis is not recommended

The most common hematologic toxicity with mezigdomide is immune-mediated thrombotic microangiopathy, requiring immediate discontinuation of mezigdomide and initiation of plasmapheresis

Grade 3/4 neutropenia is the most common hematologic TEAE and is managed by initiating G-CSF support, dose interruption, and/or dose reduction upon recovery, while monitoring closely for febrile neutropenia and secondary infections

Mezigdomide-based regimens are associated primarily with grade 3/4 peripheral neuropathy and cardiac toxicity; hematologic toxicities are uncommon

Why was the SUCCESSOR-2 Phase 3 trial result considered a landmark in multiple myeloma treatment?

It was the first trial to demonstrate that a BCMA-directed CAR-T cell therapy could be safely re-administered after prior BCMA exposure, achieving durable MRD negativity in triple-class refractory patients, including those with del(17p)

It was the first positive Phase 3 study for mezigdomide, demonstrating that MeziKd provided a statistically significant and clinically meaningful PFS improvement over Kd alone in RRMM

It was the first randomized trial to show that daratumumab re-challenge after prior anti-CD38 exposure was effective, with MeziKd serving as the control arm

It established mezigdomide as a new standard of care for newly diagnosed multiple myeloma by replacing lenalidomide as maintenance post-ASCT