FDA Approves Iberdomide Combination for Treated Myeloma

The FDA has granted accelerated approval to iberdomide (Zenbexus, Bristol Myers Squibb) with daratumumab and hyaluronidase-fihj and dexamethasone for adults with multiple myeloma after at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. Bristol Myers Squibb said Zenbexus is the first FDA-approved cereblon-modulating protein degrader (CELMoD).The action was based on EXCALIBER-RRMM, a phase 3, multicenter, two-stage, randomized, open-label trial in adults with relapsed or refractory multiple myeloma. Of 939 randomized patients, the primary efficacy population included the first 420 assigned to iberdomide 1mg plus daratumumab and hyaluronidase-fihj and dexamethasone (n=207) or daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone (n=213).

The major efficacy outcome was minimal residual disease (MRD)-negative complete response (CR) at any time. At 16 months’ median follow-up, MRD-negative CR occurred in 41% of patients with the iberdomide regimen and 21% with the comparator.

The prescribing information includes boxed warnings for embryo-fetal toxicity and serious venous and arterial thromboembolism, plus warnings for neutropenia, infections and second primary malignancies. The company reported adverse-reaction discontinuations in 7.8%, neutropenia in 90.2%, infections in 78.9% and fatal adverse reactions in 4.9% of patients receiving the iberdomide regimen. Because of embryo-fetal risk, iberdomide is available only through the Zenbexus Risk Evaluation and Mitigation Strategy.

The recommended dose is iberdomide 1mg orally once daily, with or without food, on days 1 through 21 of each 28-day cycle with daratumumab and hyaluronidase-fihj and dexamethasone; treatment continues until progression or unacceptable toxicity. The review used Project Orbis with Switzerland’s Swissmedic, and FDA granted priority review, breakthrough therapy and orphan drug designations. The trial remains ongoing to assess progression-free survival, and continued approval may depend on confirmatory verification of clinical benefit.

Sources: US Food and Drug Administration. FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma.FDA approval notification. US Food and Drug Administration; August 13, 2026. Accessed August 14, 2026.

Bristol Myers Squibb. U.S. FDA grants accelerated approval to Bristol Myers Squibb’s first CELMoD therapy Zenbexus, in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd), for patients with multiple myeloma, as early as first relapse. Press release. Bristol Myers Squibb; August 13, 2026. Accessed August 14, 2026.