Bristol Myers Squibb reports a 51% lower risk of disease progression or death with iberdomide, with median PFS of 42 months versus 20 months in Phase 3 EXCALIBER-RRMM.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Bristol Myers Squibb (BMS) has announced positive topline results from the Phase 3 EXCALIBER-RRMM study, demonstrating a statistically significant improvement in progression-free survival (PFS) with ZENBEXUS™ (iberdomide), in combination with daratumumab and dexamethasone, compared with daratumumab, bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM).
Announced on October 8, 2026, the results showed median PFS of 42 months with the iberdomide combination (ZDd), compared with 20 months with the comparator regimen (DVd). The hazard ratio (HR) was 0.49, with a p-value of less than 0.000001. According to BMS, this represents a 51% reduction in the risk of disease progression or death. Median follow-up was 23 months.
The findings meet the study’s second dual primary endpoint, PFS, building on previously reported results showing an improvement in minimal residual disease (MRD)-negative complete response with ZDd compared with DVd.
EXCALIBER-RRMM Study Design
EXCALIBER-RRMM (NCT04975997) is a multicentre, two-stage, randomized, open-label Phase 3 study evaluating the efficacy and safety of iberdomide combined with daratumumab and hyaluronidase-fihj and dexamethasone against daratumumab, bortezomib and dexamethasone.
The study enrolled adults with multiple myeloma whose disease had progressed after one or two previous lines of anti-myeloma therapy. BMS reported that the confirmatory PFS analysis included 800 patients, with 400 assigned to ZDd and 400 to DVd. An earlier publication reported 939 patients randomized across the overall study, including its dose-optimization stage. These figures refer to different study populations and should not be conflated.
Treatment in both groups continued until disease progression or unacceptable toxicity.
The dual primary endpoints were PFS and MRD-negative complete response. Secondary endpoints included overall survival, overall response rate, safety and sustained MRD negativity. The study also incorporated a dose-optimization stage to establish the iberdomide dose used in the confirmatory comparison.
Progression-Free Survival Findings
The median PFS difference between the treatment groups was 22 months in favour of ZDd. The HR of 0.49 indicates a lower hazard of disease progression or death with the iberdomide-containing regimen during the analysis period. The reported p-value provides strong statistical evidence of a difference between the groups.
PFS measures the time patients remain alive without their disease progressing. Although the difference in median PFS favoured ZDd, it does not mean that every patient receiving the combination will experience an additional 22 months without progression.
BMS has not yet released the complete dataset from this analysis. Further details will be needed to assess the results across patient subgroups and to evaluate the broader benefit-risk profile of the regimen.
Findings Build on Earlier MRD Results
The latest PFS results build on the previously reported improvement in MRD-negative complete response with ZDd compared with DVd.
In the prespecified MRD analysis, conducted after the first 420 patients had reached the required follow-up, 41.1% of patients receiving ZDd achieved an MRD-negative complete response, compared with 20.7% receiving DVd. The difference was statistically significant, with an odds ratio of 2.75 and a p-value of less than 0.0001.
These results were presented at the International Myeloma Society’s 23rd Annual Meeting in September 2026 and published simultaneously in The Lancet Oncology.
The US Food and Drug Administration (FDA) granted accelerated approval to ZENBEXUS in August 2026, based on the MRD-negative complete response findings. The subsequent PFS result provides additional evidence from the same clinical development programme.
Safety and Regulatory Context
BMS reported that the safety profile of ZENBEXUS in combination with standard therapies remained consistent with previously reported safety findings from EXCALIBER-RRMM. The October 8 topline announcement did not provide a comprehensive new breakdown of adverse events associated with the PFS analysis.
The existing US accelerated approval covers iberdomide in combination with daratumumab and hyaluronidase-fihj and dexamethasone for adults with multiple myeloma who have received at least one previous line of therapy containing a proteasome inhibitor and an immunomodulatory agent.
The approval was based on MRD-negative complete response. Continued approval may depend on verification and description of clinical benefit in confirmatory trials. The newly reported PFS findings do not, by themselves, constitute a new regulatory decision.
Full Results Readout Expected at ASH 2026
BMS plans to present the EXCALIBER-RRMM findings at the 68th Annual Meeting of the American Society of Hematology (ASH) in New Orleans. The company has stated that full study results will be shared.
The complete dataset should provide further information on efficacy and safety, allowing a more comprehensive assessment of the treatment comparison. For patients with RRMM, the reported PFS improvement is an important clinical finding, while the full results will help clarify the magnitude and broader implications of the benefit.
References
ZENBEXUS (iberdomide) in combination with daratumumab and dexamethasone demonstrates superior progression-free survival versus standard of care in relapsed and refractory multiple myeloma in Phase 3 EXCALIBER-RRMM study, Bristol Myers Squibb, October 8, 2026.
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 ID NCT04975997
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.