SUCCESSOR-2 phase III: MeziKd vs Kd for RRMM

Results from the phase III, multicenter, randomized, open-label SUCCESSOR-2 trial (NCT05552976), evaluating mezigdomide + carfilzomib + dexamethasone (MeziKd; n = 288) vs carfilzomib and dexamethasone (Kd; n = 191) for the treatment of adults with relapsed/refractory multiple myeloma (RRMM), were presented by Meletios A. Dimopoulos at the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE. Eligible patients had lenalidomide (Len)- and anti-CD38 monoclonal antibody (mAb)-exposed RRMM with progressive disease after ≥1 prior line of therapy. The primary endpoint was progression-free survival (PFS) per independent review committee (IRC), with overall survival (OS) as a key secondary endpoint. 

Key data: At a median follow-up of 10.6 months, median PFS was 18.0 months with MeziKd vs 8.3 months with Kd (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.63; p < 0.0001); this PFS benefit was maintained across all prespecified subgroups. The overall response rate (ORR) was 80.2% (complete response or better [≥CR], 26.7%) with MeziKd vs 53.4% (≥CR, 8.9%) with Kd; 12-month duration of response (DoR) was 72% vs 54%, respectively. Second PFS (PFS2) was also improved with MeziKd (23.6 months vs 13.0 months; HR, 0.53; 95% CI, 0.39–0.72), while OS was immature but favored MeziKd (HR, 0.79; 95% CI, 0.54–1.15). Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 83.7% with MeziKd vs 56.5% with Kd; no new safety signals were observed. 

Key learning: MeziKd significantly improved PFS and response rates vs Kd alone in Len- and anti-CD38 mAb-exposed RRMM, with PFS benefit in all prespecified subgroups, supporting MeziKd as a potential new standard of care across treatment settings, including community practice.