FDA Accepts NDA for Iberdomide Combination in R/R Multiple Myeloma

The FDA has accepted a new drug application (NDA) seeking approval for iberdomide plus daratumumab (Darzalex) and dexamethasone as a treatment for patients with relapsed/refractory multiple myeloma, according to a press release from the developer, Bristol Myers Squibb.¹

The agency has assigned a Prescription Drug User Fee Act date of August 17, 2026, for approving the iberdomide regimen. Additionally, the FDA conferred breakthrough therapy designation and priority review for this indication.

Supporting data for the NDA came from the phase 3 EXCALIBER-RRMM trial (NCT04975997) evaluating iberdomide plus daratumumab/dexamethasone vs daratumumab plus bortezomib (Velcade) and dexamethasone (DVd) among those with relapsed/refractory multiple myeloma. Specifically, the filing was supported by findings from a planned analysis of minimal residual disease (MRD) negativity rates.

In September 2025, developers announced that the iberdomide-based regimen yielded a statistically significant MRD negativity rate improvement vs the control arm.² Based on a recommendation from a data monitoring committee, the study was to continue without any modifications to assess patients for end points including progression-free survival (PFS), overall survival, and safety. At the time of the analysis, the safety profile of the iberdomide regimen was comparable with previous reports of each agent.

“The FDA’s acceptance of this application is a testament to the potential of iberdomide, in combination with anti-CD38 monoclonal antibodies, as a novel, potent, oral treatment option, with a manageable safety profile, for patients with multiple myeloma,” Cristian Massacesi, executive vice president and chief medical officer at Bristol Myers Squibb, stated in the press release.¹ “Furthermore, our filing for iberdomide based on the MRD end point, underscores our commitment to pioneering new ways of advancing life-saving therapies for patients living with cancer.”

As part of the 2-stage, multicenter, open-label EXCALIBER-RRMM trial, patients were randomly assigned to receive daratumumab plus iberdomide and dexamethasone across 3 dosing levels or DVd.³ Patients in the experimental arm received iberdomide at 1.0, 1.3, or 1.6 mg on days 1 to 21 of each 28-day cycle.

The trial’s primary end points were PFS and MRD-negative complete responses at any time. Secondary end points included OS, sustainability of MRD negativity, ORR, time to response, duration of response, time to progression, time to next treatment, PFS2, safety, quality of life per European Organization for Research and Treatment of Cancer - Quality of Life C30 Questionnaire, and time to maximum plasma concentration.

Patients 18 years and older with multiple myeloma and measurable disease, 1 to 2 prior lines of treatment, and documented disease progression during or after the most recent line of treatment were eligible for enrollment on the trial. Having an ECOG performance status of 0 to 2 was another requirement for study entry.

Having any condition that confounded the ability to interpret study data; plasma cell leukemia, Waldenström macroglobulinemia, or clinically significant amyloidosis; or known central nervous stem involvement with multiple myeloma was grounds for exclusion from trial enrollment. Patients were also unable to enroll if they had prior therapy with iberdomide.

“This result builds on our significant experience in both targeted protein degradation and developing new treatment options for patients living with multiple myeloma. Iberdomide represents the first of a novel class of medicines, called CELMoDs, which has the potential to create a new foundation for multiple myeloma treatment that may be combined with other therapies,” Anne Kerber, senior vice president, head of Development, Hematology, Oncology and Cell Therapy at Bristol Myers Squibb, said in a press release related to earlier findings from the EXCALIBER-RRMM study.²

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. News release. Bristol Myers Squibb. February 17, 2026. Accessed February 17, 2026. https://tinyurl.com/4c8mb6ex
2. Bristol Myers Squibb announces phase 3 EXCALIBER-RRMM study evaluating iberdomide in combination with standard therapies demonstrated a significant improvement in minimal residual disease negativity rates in relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb. September 23, 2025. Accessed February 17, 2026. https://tinyurl.com/5n9768k5
3. Open-label study comparing iberdomide, daratumumab and dexamethasone (IberDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma (RRMM) (EXCALIBER-RRMM). ClinicalTrials.gov. Updated July 10, 2025. Accessed February 17, 2026. https://tinyurl.com/mstweynn