FDA Accepts Application for Iberdomide in Multiple Myeloma Treatment

The U.S. Food and Drug Administration (FDA) has accepted a new drug application for iberdomide combined with Darzalex (daratumumab) and dexamethasone (IberDd) for the treatment of patients with relapsed or refractory multiple myeloma.

Bristol Myers Squibb, the developer of the therapy, announced that the FDA has granted a Prescription Drug User Fee Act (PDUFA) date of Aug. 17, 2026, for this indication. This move follows the FDA's decision to grant breakthrough therapy designation to iberdomide, which is part of an investigational new class of medicines called cereblon E3 ligase modulator (CELMoD) agents.

Main data that support treatment with iberdomide

The application for iberdomide is based on results from a planned analysis of minimal residual disease (MRD) negativity rates from the Phase 3 EXCALIBER-RRMM study. MRD refers to the small number of cancer cells that may remain in the body of a patient with cancer after treatment. These cells are often undetectable by conventional diagnostic methods, but modern tools such as next-generation sequencing can identify one malignant cell among 100,000 to 1,000,000 normal cells.

In the treatment of multiple myeloma, MRD assessment is a highly sensitive and clinically meaningful tool. While reaching MRD negativity does not necessarily mean all cancer cells have been eliminated, it may predict improved clinical outcomes, including longer periods of remission and survival. Because of its precision, MRD is increasingly used as a surrogate endpoint for progression-free survival (PFS) in clinical trials.

The iberdomide application is also being reviewed under the FDA’s Project Orbis initiative. This program enables the concurrent review of the drug by health authorities in several other countries, aiming to expedite access to new therapies for patients.

Phase 3 EXCALIBER-RRMM trial details

The Phase 3 EXCALIBER-RRMM trial is a multicenter, two-stage, randomized, open-label study. It was designed to evaluate the efficacy and safety of the iberdomide combination (IberDd) against a standard treatment regimen of Darza;ex, Velcade (bortezomib) and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma.

The study utilizes dual-primary endpoints:

• Minimal residual disease (MRD) negativity: Measuring the absence of remaining cancer cells at high sensitivity levels.
• Progression-free survival (PFS): Measuring the length of time patients live without their cancer getting worse.

Secondary endpoints for the trial include overall survival, overall response rate, duration of response, time to progression, time to next treatment and health-related quality of life. During stage 1 of the study, researchers identified 1.0 mg as the optimal dose of iberdomide based on safety, efficacy and how the drug moves through the body (pharmacokinetics). In stage 2, approximately 664 patients were randomized to receive either the IberDd or DVd treatment. While the current filing is based on MRD data, the trial is ongoing, and patients continue to be evaluated for progression-free survival.

Safety of iberdomide

Clinical data from the EXCALIBER-RRMM study indicate that iberdomide, when used in combination with anti-CD38 monoclonal antibodies, offers a manageable safety profile for patients with multiple myeloma. As a CELMoD agent, iberdomide is part of a research platform called targeted protein degradation. This approach is designed to degrade specific proteins that were previously considered "undruggable" by traditional means.

The 1.0 mg dose used in the phase 3 trial was specifically selected during the first stage of the study to balance efficacy with safety and pharmacokinetics. By leveraging this modality, researchers aim to provide a potent oral treatment option that effectively modulates targets within the body. Bristol Myers Squibb continues to monitor the safety of patients involved in the ongoing EXCALIBER study as they evaluate the long-term impact of this investigational protein degrader.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

References

1. “U.S. Food and Drug Administration Accepts Bristol Myers Squibb's New Drug Application for Iberdomide in Patients with Relapsed or Refractory Multiple Myeloma,”by Bristol Myers Squibb. News release; Feb. 17, 2026.

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