FDA Grants Accelerated Approval to Iberdomide Combination for Relapsed or Refractory Multiple Myeloma
Clinical Summary:
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Design/Population: EXCALIBER-RRMM was a multicenter, open-label trial evaluating iberdomide plus daratumumab and hyaluronidase and dexamethasone in adults with relapsed or refractory multiple myeloma who had received 1 or 2 prior lines of therapy.
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Key Outcomes: Iberdomide plus daratumumab and dexamethasone achieved an MRD-negative complete response rate of 41% compared with 21% with daratumumab plus bortezomib and dexamethasone (P < .0001).
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Clinical Relevance: The accelerated approval introduces iberdomide as a new oral immunomodulatory treatment option for previously treated multiple myeloma, with the combination producing substantially deeper responses than a bortezomib-based daratumumab regimen in the pivotal efficacy population.
The US Food and Drug Administration (FDA) granted accelerated approval to iberdomide (Zenbexus; Bristol-Myers Squibb) in combination with daratumumab and hyaluronidase and dexamethasone for adult patients with multiple myeloma who have received at least 1 prior line of therapy that included a proteasome inhibitor and an immunomodulatory agent.
The approval was based on findings from the EXCALIBER-RRMM trial, a multicenter, open-label trial that enrolled 939 adult patients with relapsed or refractory multiple myeloma who had received 1 or 2 prior lines of therapy. Patients with disease refractory to prior anti-CD38 monoclonal antibody therapy or bortezomib were excluded.
In stage 1, 279 patients were randomized to 1 of 3 dose levels of iberdomide in combination with daratumumab and hyaluronidase and dexamethasone or daratumumab and hyaluronidase plus bortezomib and dexamethasone. In stage 2, 660 patients were randomized to 1 mg of iberdomide plus daratumumab and hyaluronidase and dexamethasone or daratumumab and hyaluronidase plus bortezomib and dexamethasone.
The primary efficacy analysis included the first 420 patients randomized to 1 mg of iberdomide plus daratumumab and dexamethasone (n = 207) or daratumumab and hyaluronidase plus bortezomib and dexamethasone (n = 213) across stages 1 and 2. The major efficacy end point was minimal residual disease (MRD)-negative complete response at any time.
The MRD-negative complete response rate was 41% with the iberdomide combination compared with 21% with daratumumab and hyaluronidase plus bortezomib and dexamethasone (P < .0001).
The recommended dose of iberdomide is 1 mg orally once daily on days 1 through 21 of each 28-day cycle, with or without food. Iberdomide is administered with 1800 mg of subcutaneous daratumumab and hyaluronidase on days 1, 8, 15, and 22 during cycles 1 and 2; days 1 and 15 during cycles 3 through 6; and day 1 beginning with cycle 7. Dexamethasone is administered orally at 20 mg or 40 mg on days 1, 8, 15, and 22. Treatment should continue until disease progression or unacceptable toxicity.
The prescribing information for iberdomide includes a boxed warning for embryo-fetal toxicity and serious venous and arterial thromboembolism, as well as warnings and precautions for neutropenia, infections, and secondary primary malignancies. Because of the risk of embryo-fetal toxicity, iberdomide is available only through the ZENBEXUS Risk Evaluation and Mitigation Strategy program.
Source:
US Food and Drug Administration. FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma. Accessed on August 13, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-iberdomide-daratumumab-and-hyaluronidase-fihj-and-dexamethasone
