EHA / Conferences 07/22/2026

The Emerging Data for CELMoDs in Multiple Myeloma

Rahul Banerjee, MD, FACP Oncologist smiling in white coat, highlighting cancer research and treatment expertise, with a bow tie, in a bright medical setting. Rohit Gosain, MD

Key Points

  • Cereblon E3 ligase modulatory drugs (CELMoDs) are a next-generation class of agents that offer more potent activity compared with existing immunomodulatory drugs (IMIDS).
  • The addition of mezigdomide to carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) for patients with relapsed or refractory multiple myeloma in the SUCCESSOR-2 trial.

While the 31st European Hematology Association Annual Congress (EHA 2026) was underway, Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, and Rahul Banerjee, MD, FACP, of Fred Hutchinson Cancer Center, met to discuss emerging data on CELMoDs in multiple myeloma.

CELMoDs are a next-generation class of agents that offer more potent activity than conventional IMiDs, even in patients previously treated with IMiDs. Several agents are in development and under investigation in multiple myeloma trials, although none are yet approved. Two CELMoDs, iberdomide and mezigdomide, are likely to be the first agents in this class to be approved for multiple myeloma. 

CELMoDs both promote T-cell function and provide anti-myeloma activity. Studies have shown that CELMoDs reverse T-cell dysfunction and improve the efficacy of T-cell–directed treatments like bispecific antibodies or chimeric antigen receptor (CAR) T-cell therapies. Dr. Banerjee foresees that CELMoDs will be approved as part of combinations like mezigdomide plus Kd (MeziKd) or iberdomide plus daratumumab and dexamethasone. In real-world practice, however, they may be used flexibly around T-cell–based therapies.

The doctors also discussed data from the phase 3 SUCCESSOR-2 trial presented at EHA 2026. The trial evaluated MeziKd versus Kd in patients with relapsed or refractory multiple myeloma after 1 or more prior lines of therapy including an anti-CD38 monoclonal antibody and lenalidomide. Overall, the median PFS was 18 months (95% CI, 14.5-22.1) with MeziKd and 8.3 months (95% CI, 5.6-10.7) with Kd (HR, 0.48; 95% CI, 0.36-0.63; P < .0001), and the benefit was consistent across subgroups. The objective response rate was 80.2% with MeziKd versus 53.4% with Kd, and the rate of complete responses or better was 26.7% and 8.9%, respectively, according to the report. 

Although bispecifics and CAR T-cell therapies have achieved longer PFS outcomes in previous trials, MeziKd represents an extremely valuable treatment option for patients who can’t receive, or have relapsed after, bispecifics or CAR T-cell therapies, said Dr. Banerjee.