FDA Approves Iberdomide Plus Daratumumab/Dexamethasone for R/R Myeloma

The FDA has 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 supported by data from the phase 3 EXCALIBER-RRMM trial (NCT04975997), in which IberDd generated 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 rate at any time of 41% (95% CI, 34%-48%) compared with 21% (95% CI, 15%-27%) among patients treated with daratumumab plus bortezomib (Velcade) and dexamethasone (P < .0001).¹

What was the design of the EXCALIBER-RRMM trial?

The open-label, multicenter, two-stage, randomized phase 3 EXCALIBER-RRMM trial is evaluating 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 were 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

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. 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 July 7, 2026. https://news.bms.com/news/details/2025/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/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