Princeton, New Jersey, USA, October 8, 2026
Bristol Myers Squibb (BMS) has announced positive Phase 3 results for ZENBEXUS™ (iberdomide) in combination with daratumumab and dexamethasone, demonstrating a significant improvement in progression-free survival (PFS) among patients with relapsed or refractory multiple myeloma. The results from the pivotal EXCALIBER-RRMM clinical trial showed that the investigational combination, referred to as ZDd, outperformed the comparator regimen of daratumumab, bortezomib and dexamethasone (DVd). The study evaluated 800 patients with multiple myeloma, including patients treated as early as their first relapse. After a median follow-up of 23 months, the median progression-free survival was 42 months with ZDd compared with 20 months with DVd, representing a 51% reduction in the risk of disease progression or death. These findings build on earlier results demonstrating improved minimal residual disease (MRD)-negative complete response rates and provide additional evidence supporting the clinical benefit of the ZENBEXUS-based combination. The data are expected to be presented at the 68th Annual Meeting of the American Society of Hematology (ASH) in New Orleans, Louisiana.
Phase 3 EXCALIBER-RRMM Trial Shows Improved Survival Outcomes
The EXCALIBER-RRMM study is a randomized, open-label Phase 3 trial designed to assess the efficacy and safety of ZENBEXUS combined with daratumumab and dexamethasone against the DVd regimen in adults with relapsed or refractory multiple myeloma. The confirmatory progression-free survival analysis included 800 randomized patients, with 400 assigned to each treatment group. The study’s results demonstrated a statistically significant improvement in PFS, with a hazard ratio of 0.49 and a p-value below 0.000001. The 51% reduction in the risk of disease progression or death represents an important finding for patients whose disease has returned or failed to respond adequately to previous therapies. Median PFS of 42 months in the ZDd group compared with 20 months in the DVd group indicates a substantial difference in the time patients remained alive without disease progression. The trial also evaluates overall survival, overall response rate, safety and the durability of MRD-negative responses. These additional measures will help researchers understand the full clinical impact of the treatment combination. Although the PFS results are encouraging, overall survival outcomes and longer-term follow-up remain important considerations in determining the treatment’s broader clinical value.
Iberdomide Combination Builds on MRD Response Findings
ZENBEXUS contains iberdomide, a cereblon E3 ligase modulator (CELMoD) designed to promote the degradation of specific proteins involved in multiple myeloma cell survival. The combination also includes daratumumab, which targets CD38 on plasma cells, and dexamethasone, a corticosteroid used in myeloma treatment. Together, these medicines use complementary mechanisms to target malignant plasma cells and strengthen treatment activity. Earlier EXCALIBER-RRMM findings showed that ZDd achieved a higher rate of MRD-negative complete response than DVd, with results of 41.1% versus 20.7%, respectively. MRD negativity indicates that cancer cells cannot be detected in bone marrow samples using sensitive testing methods and is considered a meaningful measure of treatment depth. The new PFS findings strengthen the evidence that the earlier response improvements translated into a longer period without disease progression. BMS reported that the combination’s safety profile remained consistent with previously reported findings. However, treatment decisions require careful consideration of individual patient factors, possible adverse events and the risks associated with each medicine. The company plans to share the detailed results with the hematology community, providing further information about the regimen’s clinical performance.
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BMS Advances Treatment Options for Multiple Myeloma
Multiple myeloma is a blood cancer that develops from abnormal plasma cells in the bone marrow. Despite advances in treatment, the disease frequently returns, creating a need for additional therapeutic approaches that can provide durable disease control. ZENBEXUS received accelerated U.S. FDA approval in August 2026 in combination with daratumumab and hyaluronidase-fihj and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy that included a proteasome inhibitor and an immunomodulatory agent. The approval was based on MRD-negative complete response findings, while confirmation of clinical benefit through progression-free survival remains important for continued approval. The latest EXCALIBER-RRMM results provide further evidence for the combination in this patient population. BMS continues to evaluate iberdomide in additional clinical settings, including maintenance treatment research. The positive Phase 3 PFS results represent a significant development in multiple myeloma research, although ongoing safety monitoring, regulatory review and additional analyses will remain essential. The findings could help inform future treatment strategies for patients requiring effective options after previous therapies have failed.
Source: Bristol Myers Squibb press release
