FDA Approves Bristol Myers' First CELMoD for Myeloma

FDA granted accelerated approval on 13 August 2026 to iberdomide, sold as Zenbexus by Bristol Myers Squibb, opening up a new drug class for multiple myeloma. Used with daratumumab, hyaluronidase-fihj, and dexamethasone, it is the first approved cereblon E3 ligase modulator, or CELMoD, and the first drug in that class cleared for patients as early as their first relapse.

A new mechanism, not a new entrant

Multiple myeloma already has a crowded field of immunomodulatory drugs, but CELMoDs are mechanistically distinct from the lenalidomide-and-pomalidomide generation that came before them, engineered for more selective degradation of the transcription factors that drive myeloma cell survival. Iberdomide's approval is the first time FDA has cleared a drug in that class for marketing, which makes Zenbexus a reference point rather than a follow-on: how FDA frames its labeling, safety monitoring requirements, and post-marketing commitments here will likely shape what sponsors of the next CELMoD candidates in development are asked to show.

Where it fits in the treatment line

The approved indication is for adults with multiple myeloma who have received at least one prior line of therapy that included both a proteasome inhibitor and an immunomodulatory agent — putting the ZDd regimen in play as early as a patient's first relapse, rather than reserved for later, more heavily pretreated lines. That positioning matters for how quickly the regimen can be adopted into treatment algorithms and how directly it competes with existing early-relapse standards, including the DVd regimen it was measured against in the pivotal trial.

The evidence, and the strings attached

EXCALIBER-RRMM is a two-stage, randomized, multicenter, open-label phase 3 trial in adults with relapsed or refractory multiple myeloma who had received one or two prior lines of therapy, comparing ZDd against DVd. An interim analysis showed the ZDd arm achieving higher rates of minimal residual disease negativity — a marker of depth of response that FDA accepted as the basis for accelerated approval rather than waiting for mature overall-survival or progression-free-survival data. As with every accelerated approval, that acceptance comes with a condition: FDA's approval announcement states that continued marketing authorization may depend on confirmatory trials verifying that the MRD-negativity benefit translates into the clinical outcomes accelerated approval is meant to predict.