Dr Berdeja on the Potential Role of CELMoDs in Multiple Myeloma Management

[Both] iberdomide and mezigdomide, in their prospective studies, are showing that when you combine them with our standard treatments, they are much more powerful drugs compared [with] our standard of care. I do think that they are well poised to have a role in replacing some of our standard-of-care options.

Jesús Berdeja, MD, director of Multiple Myeloma Research at Sarah Cannon Research Institute and Tennessee Oncology, discussed the potential role of CELMoDs, including iberdomide (Zenbexus) and mezigdomide (CC-92480), in multiple myeloma management, and why this class could displace some agents in current standard-of-care regimens.

According to Berdeja, CELMoDs are the most exciting class of immunotherapy outside of T-cell–redirecting approaches to emerge in recent years, as much of the field’s attention has centered on CAR T-cell therapies and bispecific antibodies. He explained that CELMoDs are specifically designed to target cereblon, which makes them much more potent than the immunomodulatory drugs (IMiDs), as well as more potent activators of the immune system. Those 2 qualities make CELMoDs powerful drugs, he explained.

In August 2026, the FDA granted accelerated approval to iberdomide plus daratumumab and hyaluronidase-fihj (Darzalex Faspro) and dexamethasone (IberDd) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent. The decision was supported by data from the phase 3 EXCALIBER-RRMM trial (NCT04975997), in which the minimal residual disease (MRD)–negative complete response rate was 41% (95% CI, 34%-48%) with IberDd (n = 207) vs 21% (95% CI, 15%-27%) with daratumumab, bortezomib (Velcade), and dexamethasone (P < .0001).

Findings from the phase 3 SUCCESSOR-2 trial (NCT05552976), presented at the 2026 ASCO Annual Meeting, showed that mezigdomide plus carfilzomib (Kyprolis) and dexamethasone (n = 288) generated a median progression-free survival (PFS) of 18.0 months vs 8.3 months with carfilzomib and dexamethasone alone (n = 191; HR, 0.48; 95% CI, 0.36-0.63; P < .001) in patients with relapsed/refractory multiple myeloma previously treated with lenalidomide (Revlimid) and an anti-CD38 antibody. The overall response rate was 80.2% vs 53.4%, respectively.

Combining a CELMoD with standard backbone therapies has outperformed the existing standard of care in prospective studies, Berdeja noted. As a result, he concluded that CELMoDs are well positioned to take on a role in replacing some current standard-of-care options in multiple myeloma.