FDA Grants Accelerated Approval to Iberdomide Combination for Relapsed Multiple Myeloma
On August 13, 2026, the U.S. Food and Drug Administration (FDA) granted accelerated approval to iberdomide (Zenbexus) in combination with daratumumab, hyaluronidase-fihj, and dexamethasone (ZDd) for adults with multiple myeloma who have received at least one prior line of therapy that included a proteasome inhibitor and an immunomodulatory agent.
The approval introduces the first FDA-approved CELMoD (cereblon E3 ligase modulator) therapy for multiple myeloma, adding a new treatment option that may be used as early as first relapse.
EXCALIBER-RRMM Results Support Approval
The accelerated approval was based on findings from the phase 3 EXCALIBER-RRMM trial, which evaluated ZDd against daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma.
At a median follow-up of 16 months, 41% of patients receiving ZDd achieved minimal residual disease (MRD)-negative complete response, compared with 21% of patients receiving DVd, meeting one of the study’s dual primary endpoints (P < 0.0001).
The FDA’s decision represents the first accelerated approval in relapsed or refractory multiple myeloma based on MRD-negative complete response. The EXCALIBER-RRMM study remains ongoing, with progression-free survival—the trial’s other primary endpoint—still being evaluated.
A New Therapeutic Class in Multiple Myeloma
Iberdomide is a next-generation oral CELMoD agent designed to enhance cereblon-mediated degradation of the transcription factors Ikaros and Aiolos. Its approval expands the role of targeted protein degradation in multiple myeloma and introduces a new therapeutic class into the relapsed disease setting.
The ZDd regimen was associated with a safety profile consistent with its component therapies. Key safety considerations include severe neutropenia and serious infections. ZENBEXUS also carries boxed warnings for embryo-fetal toxicity and venous and arterial thromboembolism, and is contraindicated during pregnancy.
Because the indication was granted under the FDA’s accelerated approval pathway, continued approval may depend on confirmation of clinical benefit in ongoing or future studies.
The approval provides clinicians with another treatment option for patients experiencing multiple myeloma relapse and establishes CELMoD therapy as a new component of the evolving multiple myeloma treatment landscape.
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The Emerging Data for CELMoDs in Multiple Myeloma: Explore the emerging clinical data for CELMoD therapies and their potential role in the evolving multiple myeloma treatment algorithm.
5 Key Multiple Myeloma Trial Updates from EHA 2026: Review five important multiple myeloma trial updates from EHA 2026 and their potential implications for clinical practice.