Dive into the Data Supporting the FDA Approval of Iberdomide Plus Daratumumab/Dexamethasone in R/R Myeloma

On August 13, 2026, the FDA granted accelerated approval to iberdomide (Zenbexus) plus daratumumab and hyaluronidase-fihj (Darzalex Faspro) and dexamethasone (IberDd) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.¹

The regulatory decision was backed by data from the phase 3 EXCALIBER-RRMM trial (NCT04975997), which showed that IberDd produced a statistically significant improvement in minimal residual disease (MRD) negativity rates vs daratumumab plus bortezomib (Velcade) and dexamethasone (DVd).^1,2

Findings supporting the approval showed that patients in the IberDd arm (n = 207) achieved an MRD-negative complete response rate at any time of 41% (95% CI, 34%-48%) compared with 21% (95% CI, 15%-27%) among patients treated with daratumumab plus bortezomib and dexamethasone (P < .0001).¹

The accelerated approval marked the first publicly reported data from EXCALIBER-RRMM after it was previously announced in September 2025 tthat the study produced positive topline findings.³

Check out the slideshow above to take a look at the design of EXCALIBER-RRMM, along with key efficacy and safety data supporting the FDA’s accelerated approval.

How was EXCALIBER-RRMM conducted?

The open-label, multicenter, two-stage, randomized phase 3 EXCALIBER-RRMM trial evaluated IberDd vs DVd in patients with relapsed or refractory multiple myeloma who have received 1 to 2 prior lines of antimyeloma therapy.³ Patients who are refractory to CD38-targeted antibody therapy or to bortezomib are excluded.

In stage 1, the dose-optimization phase, patients were randomly assigned 1:1:1:1 to receive iberdomide at 1.0 mg, 1.3 mg, or 1.6 mg plus daratumumab and dexamethasone, or to DVd; the 1.0-mg dose of iberdomide was selected for continued evaluation based on safety, pharmacokinetic, and efficacy data. In stage 2, approximately 664 patients were randomized 1:1 to IberDd in 28-day cycles or DVd in 21- or 28-day cycles. Stratification factors included number of prior lines of therapy (1 vs 2), age (≤ 70 years vs > 70 years), and International Staging System stage at study entry (I or II vs III).

The trial’s dual primary end points comprised MRD negativity and progression-free survival (PFS). Secondary end points included overall survival, overall response rate (ORR), duration of response, time to progression, time to next treatment, and health-related quality of life. The trial remains ongoing, with patients continuing to be evaluated for PFS following the MRD analysis that supported the NDA.^1,2

What safety data were reported for the combination?

Adverse effects (AEs) led to treatment discontinuation in 7.8% of patients treated with IberDd.²

The most common AEs reported in at least 20% of patients treated with IberDd and DVd arms, respectively, were upper respiratory tract infection (54% vs 52%), fatigue (36% vs 33%), musculoskeletal pain (35% vs 33%), pneumonia (34% vs 17%), diarrhea (33% vs 36%), motor dysfunction (26% vs 17%), rash (26% vs 15%), sleep disorder (25% vs 28%), hypogammaglobulinemia (24% vs 12%), COVID-19 (23% vs 16%), and constipation (20% vs 22%).

References

1. FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma. FDA. August 13, 2026. Accessed August 13, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-iberdomide-daratumumab-and-hyaluronidase-fihj-and-dexamethasone
2. 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. News release. Bristol Myers Squibb. August 13, 2206. Accessed August 13, 2026. https://news.bms.com/news/corporate-financial/2026/U-S--FDA-Grants-Accelerated-Approval-to-Bristol-Myers-Squibbs-First-CELMoD-Therapy-ZENBEXUS-in-Combination-with-Daratumumab-and-Hyaluronidase-fihj-and-Dexamethasone-ZDd-for-Patients-with-Multiple-Myeloma-as-Early-as-First-Relapse/default.aspx
3. Lonial S, Dimopoulos MA, Berdeja JG, et al. EXCALIBER-RRMM: a phase III trial of iberdomide, daratumumab, and dexamethasone in relapsed/refractory multiple myeloma. Future Oncol. 2025;21(14):1761-1769. doi:10.1080/14796694.2025.2501920