BMS Reports 42-Month Progression-Free Survival with ZENBEXUS Combination in Multiple Myeloma Trial

Bristol Myers Squibb (BMS) has announced positive results from its Phase III EXCALIBER-RRMM study evaluating ZENBEXUS (iberdomide) in combination with daratumumab and dexamethasone (ZDd) for patients with relapsed or refractory multiple myeloma. The combination was compared against the standard-of-care regimen of daratumumab, bortezomib, and dexamethasone (DVd).

Key Clinical Trial Results (EXCALIBER-RRMM)

Progression-Free Survival (PFS): The ZDd combination achieved a median PFS of 42 months, compared to 20 months for the DVd comparator regimen.
Risk Reduction: This improvement represents a statistically significant 51% reduction in the risk of disease progression or death, with a hazard ratio of 0.49 and a p-value of less than 0.000001 (at a median follow-up of 23 months).
Study Scope: The confirmatory PFS analysis encompassed 800 patients, split evenly with 400 participants in each treatment arm.
Minimal Residual Disease (MRD): Earlier results from the study showed an MRD-negative complete response rate of 41.1% for ZDd compared to 20.7% for DVd.

Mechanism and Regulatory Status

ZENBEXUS (Iberdomide): An oral cereblon E3 ligase modulator (CELMoD) designed to target multiple myeloma via cereblon-related mechanisms and modulate immune responses.
Combination Regimen: Integrates iberdomide with daratumumab (a CD38-targeted monoclonal antibody) and dexamethasone (a corticosteroid).
Regulatory Status: ZENBEXUS in combination with daratumumab and hyaluronidase-fihj and dexamethasone received accelerated approval from the U.S. FDA on August 13, 2026, for adults with multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.
Next Steps: BMS plans to present detailed results from the EXCALIBER-RRMM trial at the upcoming 68th Annual Meeting of the American Society of Hematology in New Orleans.