Dr Richter on Where CELMoDs Could Fit in the Myeloma Treatment Paradigm

“[Potentially], mezigdomide is going to be for the really bad stuff, [such as EMD], and iberdomide may be a great long-term maintenance strategy.”

Joshua Richter, MD, director of Multiple Myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai and an associate professor of medicine at The Tisch Cancer Institute, broke down the potential roles for the cerebron E3 ligase modulatory drugs (CELMoDs) iberdomide (CC-220) and mezigdomide (CC-92480) for patients with multiple myeloma, based on early clinical trial data for the respective agents.

Richter began by noting that iberdomide could serve as a maintenance therapy for patients with multiple myeloma who have recently received CAR T-Cell therapy or autologous stem cell transplant (ASCT), explaining that early safety data point to iberdomide being better tolerated long term.

Richter highlighted data from the phase 2 EMN 26 trial (NCT04564703), where iberdomide was evaluated in patients with multiple myeloma who had recently undergone ASCT. Richter added that iberdomide demonstrated minimal residual disease (MRD)–negativity conversion rates of 30% to 50% in the trial, depending on the dose, whereas some of the best historical lenalidomide data have MRD-negativity conversion rates ranging from approximately 10% to 20%. Iberdomide is similar to lenalidomide except with a better myelotoxicity profile, according to Richter.

Moreover, iberdomide has shown promising data when combined with other drugs like elranatamab-bcmm (Elrexfio) in the phase 1b MagnetisMM-30 trial(NCT06215118),which was presented at the 2025 Annual Meeting and Exposition. Findings showed the combination yielded an objective response rate of 95.5% (95% CI, 77.2%-99.9%) in patients with relapsed or refractory multiple myeloma (n = 22).

Richter shifted to mezigdomide, noting that it is the more potent drug out of the two CELMoDs under evaluation and how it is suitable for different scenarios. Richter outlined patients with multiple myeloma and extramedullary disease (EMD) could be optimal patients to receive mezigdomide. The phase 1/2 RedirecTT-1 study (NCT04586426), which evaluated the combination of talquetamab-tgvs (Talvey) and teclistamab-cqyv (Tecvayli) as a treatment for EMD, showcased the combination as effective but impractical, Richter said. Richter then added that other trials evaluating the combination of mezigdomide and dexamethasone in EMD have displayed deep remissions.