Bristol Myers Squibb (BMY) reported that its investigational drug iberdomide, branded Zenbexus, achieved markedly better outcomes when added to daratumumab and dexamethasone in patients with relapsed or refractory multiple myeloma. The results were disclosed at the 23rd Annual Meeting of the International Myeloma Society in Glasgow and published in The Lancet Oncology.
The phase 3 EXCALIBER‑RRMM trial enrolled 939 participants who had received one or two prior anti‑myeloma therapies. Of these, 420 patients had a median follow‑up of 15.7 months and were evaluated for efficacy and safety. A confirmatory cohort of 800 patients continues to be monitored for progression‑free survival.
In the experimental arm, the triplet regimen of Zenbexus, daratumumab and dexamethasone produced a minimal residual disease‑negative complete response (MRD‑neg CR) rate of 41.1%, compared with 20.7% for the control regimen of daratumumab, bortezomib and dexamethasone. Overall response rates were 88.9% versus 76.1%, and complete response or better was observed in 45.9% of patients versus 24.9% with the comparator.
Safety findings reflected higher hematologic toxicity with the Zenbexus combination. Grade 3 or 4 neutropenia occurred in 84.3% of patients, largely during the first two cycles, versus 11.3% in the control group. Grade 3/4 infections were reported in 39.2% versus 21.6%, and fatal infections in 2.0% versus 1.5%. Conversely, any‑grade peripheral sensory neuropathy was lower with Zenbexus (12.3% versus 42.6%).
The drug received accelerated FDA approval on August 13 for adult multiple myeloma patients who have undergone at least one prior line of therapy that included a proteasome inhibitor and an immunomodulatory agent. Continued approval will depend on verification of clinical benefit in ongoing confirmatory trials.
The data suggest that Zenbexus may offer a more effective treatment option for heavily pre‑treated myeloma patients, though the increased risk of severe neutropenia and infections will require careful management.
