SUCCESSOR-2 data showed MeziKd prolonged progression-free survival in relapsed or refractory multiple myeloma at ASCO 2026.
SUCCESSOR-2 Multiple Myeloma Data Show PFS Benefit
Results presented at ASCO 2026 showed that mezigdomide, carfilzomib, and dexamethasone, known as MeziKd, significantly improved progression-free survival compared with carfilzomib and dexamethasone alone in patients with relapsed or refractory multiple myeloma.
The phase 3 SUCCESSOR-2 trial evaluated MeziKd in a high-risk population with limited treatment options. Eligible adults had received at least one prior line of therapy, including both an anti-CD38 monoclonal antibody and lenalidomide. The study reflects a clinically important treatment setting, as increasing numbers of patients entering second-line treatment have already been exposed to these agents.
SUCCESSOR-2 used a two-stage, inferentially seamless design. In stage 1, patients were randomized to receive one of three mezigdomide doses with carfilzomib and dexamethasone, or carfilzomib and dexamethasone alone. The 1.0 mg dose of mezigdomide was selected for stage 2.
MeziKd Doubles Median Progression-Free Survival
The analysis included 479 patients, comprising 288 patients who received MeziKd with 1.0 mg mezigdomide and 191 who received carfilzomib and dexamethasone alone. Median age was 68 years, and 25.1% of patients were aged 75 years or older. Patients had received a median of two prior lines of therapy, with 92.1% triple-class-exposed, 85.8% refractory to an anti-CD38 monoclonal antibody, and 75.8% refractory to lenalidomide.
MeziKd significantly improved median progression-free survival versus carfilzomib and dexamethasone alone, at 18.0 months compared with 8.3 months. This represented a 52% reduction in the risk of progression or death, with a hazard ratio of 0.48 and a P value below 0.0001.
The progression-free survival benefit was consistent across key subgroups, including patients with more than two prior lines of therapy, prior treatment exposure or refractoriness, high-risk cytogenetics, extramedullary disease, and age 75 years or older.
Response Rates Rise With MeziKd
Overall response rate was higher with MeziKd than with carfilzomib and dexamethasone alone, at 80.2% versus 53.4%. Complete response or better was also more frequent with MeziKd, reported in 26.7% of patients compared with 8.9% in the control arm.
At data cutoff, median follow-up was 10.6 months. More patients remained on treatment with MeziKd than with carfilzomib and dexamethasone alone, at 52.4% versus 31.4%. Median treatment duration was 8.9 months with MeziKd and 6.2 months with carfilzomib and dexamethasone alone.
Safety Profile Requires Monitoring
Grade 3 or 4 treatment-emergent adverse events were more common with MeziKd than with carfilzomib and dexamethasone alone, at 83.7% versus 56.5%. Neutropenia occurred in 61.1% versus 9.1%, and infections occurred in 34.0% versus 15.6%, respectively. Grade 5 infections were uncommon in both groups, reported in 2.4% and 1.1%.
Deaths were reported in 21.5% of patients receiving MeziKd and 26.7% receiving carfilzomib and dexamethasone alone, mostly due to progressive disease. The findings support MeziKd as a potential new standard treatment option for relapsed or refractory multiple myeloma across multiple clinical settings.
Reference
Richardson PG et al. Mezigdomide, carfilzomib, and dexamethasone (MeziKd) vs carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM): Results from the phase 3 SUCCESSOR-2 trial. ASCO Annual Meeting, May 29-June 2, 2026.
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