PRINCETON, N.J. — September 26, 2026
Bristol Myers Squibb announced the first presentation of results from the pivotal Phase 3 EXCALIBER-RRMM trial evaluating ZENBEXUS™ (iberdomide) in combination with daratumumab and dexamethasone (ZDd) in patients with relapsed or refractory multiple myeloma (RRMM). At a median follow-up of 15.7 months, the regimen produced a statistically significant improvement in the trial’s MRD-negative complete response (CR) rate, with 41.1% of evaluable patients receiving ZDd achieving an MRD-negative CR compared with 20.7% receiving daratumumab, bortezomib and dexamethasone (DVd) (p<0.0001; odds ratio 2.75). The results were presented at the International Myeloma Society 2026 meeting in Glasgow and simultaneously published in The Lancet Oncology. The second dual-primary endpoint, progression-free survival (PFS), remains under evaluation.
ZENBEXUS Triplet Delivers Deeper Responses in RRMM
The EXCALIBER-RRMM study enrolled 939 patients, with the primary MRD-negative CR efficacy analysis based on the first 420 randomized patients. Patients had received one to two prior lines of anti-myeloma therapy and were randomized to ZDd or DVd. In addition to the MRD-negative CR benefit, the overall response rate was 88.9% with ZDd versus 76.1% with DVd, while complete response or better was achieved by 45.9% and 24.9% of patients, respectively. According to Bristol Myers Squibb, the treatment effect on MRD-negative CR was consistent across prespecified subgroups, including patients previously exposed or refractory to lenalidomide. The findings support further evaluation of iberdomide-based treatment in patients with relapsed or refractory disease, including those experiencing their first relapse.
Safety Profile Reflects Increased Hematologic Toxicity
Grade 3/4 neutropenia occurred in 84.3% of patients receiving ZDd compared with 11.3% receiving DVd, with the majority of neutropenia occurring during the first two treatment cycles. Bristol Myers Squibb reported that neutropenia was generally managed with G-CSF support and temporary treatment interruptions; ZENBEXUS dose reduction due to neutropenia occurred in 13.2% of patients and discontinuation due to neutropenia in 1.0%. Grade 3/4 infections occurred in 39.2% of patients in the ZDd arm versus 21.6% in the DVd arm, while fatal infections were reported in 2.0% and 1.5%, respectively. In contrast, peripheral sensory neuropathy was less frequent with ZDd, occurring in 12.3% of patients at any grade compared with 42.6% with DVd, while Grade 3/4 events occurred in 2.9% and 5.4%, respectively.
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ZENBEXUS Builds on Accelerated FDA Approval
ZENBEXUS in combination with daratumumab and hyaluronidase-fihj and dexamethasone received accelerated FDA approval 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. The approval was based on MRD-negative CR at any time, with continued approval contingent on verification and description of clinical benefit in confirmatory trial or trials. EXCALIBER-RRMM is designed around dual primary endpoints of MRD-negative CR rate and PFS, and the confirmatory PFS analysis in a cohort of approximately 800 patients remains ongoing. ZENBEXUS is a cereblon E3 ligase modulator (CELMoD) and part of Bristol Myers Squibb’s broader targeted protein degradation strategy in hematologic malignancies. The newly presented MRD results provide additional clinical evidence for the ZENBEXUS-based regimen, while longer-term PFS and other outcomes will further define its clinical benefit.
Source :Bristol Myers Squibb, press release
