Clinical Summary: 

• Design/Population: The phase 3 SUCCESSOR-2 trial randomized heavily pretreated patients with relapsed or refractory multiple myeloma to receive either mezigdomide plus carfilzomib and dexamethasone or carfilzomib and dexamethasone.
• Key Outcomes: Mezigdomide plus carfilzomib and dexamethasone significantly improved progression-free survival and response compared with carfilzomib and dexamethasone, with an increased but manageable toxicity profile. 
• Clinical Relevance: These findings support mezigdomide-based therapy as a potential new treatment option following anti-CD38 and lenalidomide exposure.

Results from the phase 3 SUCCESSOR-2 trial demonstrated that mezigdomide plus carfilzomib and dexamethasone significantly improved outcomes compared with carfilzomib and dexamethasone alone among heavily pretreated patients with relapsed or refractory multiple myeloma.  

These results were presented by Meletios Dimopoulos, MD, National and Kapodistrian University, Athens, Greece, at the 2026 European Hematology Association (EHA) Congress in Stockholm, Sweden. 

In this study, 479 patients with who received at least 1 prior line of therapy, including an anti-CD38 monoclonal antibody and lenalidomide, were randomized to receive 56 mg/m² of once weekly carfilzomib and  40 mg of once weekly dexamethasone either alone (n = 191) or with 1 mg of mezigdomide, on days 1 through 21 of each 28-day cycle. The primary end point was progression-free survival (PFS). Key secondary end points included objective response rate (ORR) and safety. 

At a median follow-up of 10.6 months, median PFS was 18 months in the mezigdomide arm and 8.3 months in the control arm (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36 to 0.63; P < .0001). The PFS benefit was consistent across clinically relevant subgroups, including patients with more than 2 prior lines of therapy, high-risk cytogenetics, extramedullary disease, and age 75 years or older. The ORR was 80.2% in the mezigdomide arm and 53.4% in the control arm. Complete response or better was achieved in 26.7% and 8.9% of patients, respectively.

The median treatment duration was 8.9 months in the mezigdomide arm and 6.2 months in the control arm, with 52.4% and 31.4% of patients still on study treatment. 

Grade 3/4 treatment-emergent adverse events were reported in 83.7% of patients in the mezigdomide arm and 56.5% of patients in the control arm. The most frequently reported grade 3/4 events included neutropenia (61.1% vs 9.1%) and infections (34% vs 15.6%). Treatment-related infections led to death in 2.4% and 1.1% of patients, respectively. Progressive disease led to death in 21.5% of patients in the mezigdomide arm and 26.7% of paitents in the control arm. 

“These data support [mezigdomide], a potent oral treatment with a predictable and manageable safety profile, as a readily accessible, potential new standard of care for [relapsed or refractory multiple myeloma] across multiple settings,” concluded Dr Dimopoulos. 

Source: 

Dimopoulos MA, Schjesvold F, Fu C, et al. Mezigdomide, carfilzomib, and dexamethasone (MeziKd) vs carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myelma (RRMM): Results from the phase 3 SUCCESSOR-2 trial. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-7170.