The SUCCESSOR-2 trial evaluated the efficacy and safety of mezigdomide in combination with carfilzomib and dexamethasone versus carfilzomib plus dexamethasone in patients with relapsed or refractory multiple myeloma. Mezigdomide–carfilzomib–dexamethasone significantly improved progression-free survival compared with carfilzomib–dexamethasone, with a median progression-free survival of 18.0 months versus 8.3 months. While the mezigdomide triplet led to a higher incidence of grade 3 or 4 adverse events, these were generally manageable with standard clinical practice and supportive care.
Study
|
Randomized, open-label, phase 3 controlled trial [SUCCESSOR-2, NCT05552976] |
| Relapsed/refractory multiple myeloma who received at least one previous regimen (including anti-CD38 antibodies and lenalidomide) and documented disease progression |
| Mezigdomide+Carfilzomib+Dexamethasone (n=288) vs Carfilzomib+Dexamethasone (n=191)
|
Efficacy
|
CR or better: 27% vs 9% (mezigdomide + Cd vs. Cd alone) |
| VGPR or better: 60% vs 31% |
| ORR: 80% vs 53% |
| mPFS: 18.0 mos [14.5-22.1] vs 8.3 mos [5.6-10.7] (HR 0.48 [0.36-0.63]) |
| mPFS2: 23.6 mos [18.2-NR] vs 13.0 mos [10.8-18.1] (HR 0.53 [0.39-0.72]) |
| mOS: Not reached vs Not reached (HR 0.79 [0.54-1.15])
|
Safety
|
Grade >=3 AE: neutropenia (61% vs 9%), infections (34% vs 16%), thrombocytopenia (39% vs 23%), pneumonia (16% vs 6%), febrile neutropenia (8% vs 0%) |
| Serious AEs: 65% vs 34% |
| Treatment-related deaths: 3% vs 1% |
| Discontinuation due to AE: 10% vs 6%
|
Lancet. Published online June 14, 2026
http://doi.org/10.1016/S0140-6736(26)01088-3
Reviewed by Ulas D. Bayraktar, MD on Aug 13, 2026
