Dr. Joshua Richter, director of Multiple Myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai, recently outlined the potential applications of cerebron E3 ligase modulatory drugs (CELMoDs) such as iberdomide (CC-220) and mezigdomide (CC-92480) in treating multiple myeloma. His insights were based on early clinical trial data, which suggest promising outcomes for these therapies.
Richter indicated that iberdomide may serve as an effective maintenance therapy for patients who have recently undergone CAR T-Cell therapy or autologous stem cell transplants (ASCT). He pointed to early safety data indicating that iberdomide is better tolerated over the long term compared to existing treatments. Notably, data from the phase 2 EMN 26 trial (NCT04564703) revealed that iberdomide achieved minimal residual disease (MRD)–negativity conversion rates of between 30% and 50%, depending on the dosage. In contrast, historical data for lenalidomide show MRD-negativity conversion rates of approximately 10% to 20%. Richter characterized iberdomide as similar to lenalidomide but with a superior myelotoxicity profile.
Promising Early Data on Iberdomide and Mezigdomide
Iberdomide has also demonstrated encouraging results when combined with other therapies. In the phase 1b MagnetisMM-30 trial (NCT06215118), presented at the 2025 Annual Meeting and Exposition, the combination of iberdomide with elranatamab-bcmm (Elrexfio) yielded an impressive objective response rate of 95.5% (95% CI, 77.2%-99.9%) in patients with relapsed or refractory multiple myeloma (n = 22).
Shifting focus to mezigdomide, Richter highlighted its potential as a more potent option among the CELMoDs currently being evaluated. He noted that mezigdomide could be particularly beneficial for patients with multiple myeloma who also present with extramedullary disease (EMD). The phase 1/2 RedirecTT-1 study (NCT04586426), which assessed the combination of talquetamab-tgvs (Talvey) and teclistamab-cqyv (Tecvayli) for treating EMD, showed effectiveness but was deemed impractical for broader application.
Richter emphasized the need for further research, stating that other trials involving the combination of mezigdomide and dexamethasone in patients with EMD have demonstrated the potential for achieving deep remissions. As the landscape of multiple myeloma treatment evolves, the advancement of CELMoDs could represent a significant shift in therapeutic strategies for this challenging disease.