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Mezigdomide + elranatamab is a combination therapy being developed by Bristol Myers Squibb for the treatment of relapsed/refractory multiple myeloma (RRMM). The regimen consists of mezigdomide, an oral Cereblon E3 Ligase Modulator (CELMoD), and elranatamab, a bispecific T-cell engager targeting B-cell maturation antigen (BCMA) and CD3. Mezigdomide acts as a molecular glue that binds to the Cereblon E3 ligase complex, facilitating the recruitment and subsequent proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). This degradation leads to direct apoptosis of myeloma cells and stimulates immune effector cells. Elranatamab (marketed as Elrexfio) simultaneously binds to BCMA on the surface of multiple myeloma cells and CD3 on T-cells, bridging them to induce T-cell mediated cytotoxicity. The combination is currently being evaluated in the Phase 1b/2a MELT-MM clinical trial (NCT06645678) to establish the recommended dose and assess preliminary efficacy in patients who have received multiple prior lines of therapy.
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