Clinical Summary: 

• Design/Population: In the phase 3 SUCCESSOR-2 trial, patients with relapsed/refractory multiple myeloma who had received at least 1 prior line of therapy, including an anti-CD38 monoclonal antibody and lenalidomide, were randomized to receive either mezigdomide plus carfilzomib and dexamethasone or carfilzomib plus dexamethasone.
• Key Outcomes: Mezigdomide significantly improved progression-free survival and response rates compared with carfilzomib plus dexamethasone. 
• Clinical Relevance: These findings support mezigdomide-based therapy as a potential new standard treatment option for patients with relapsed/refractory multiple myeloma previously exposed to anti-CD38 therapy and lenalidomide.

Results from the phase 3 SUCCESSOR-2 trial demonstrated that mezigdomide plus carfilzomib and dexamethasone significantly improved progression-free survival (PFS) among previously treated patients with relapsed or refractory (R/R) multiple myeloma. 

These results were presented by Paul Richardson, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this study, 479 patients who received at least 1 prior line of therapy that included both an anti-CD38 monoclonal antibody and lenalidomide were randomized 3:2 to receive 56 mg/m² of carfilzomib and 40 mg of dexamethasone once weekly either alone (n = 191) or in combination with 1 mg of mezigdomide on days 1 through 21 in 28-day cycles (n = 288). The primary end point was PFS. Secondary end points included overall 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 dexamethasone arm (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36 to 0.63; P < .0001). The PFS benefit was consistent across prespecified subgroups, including patients with more than 2 prior lines of therapy, high-risk cytogenetics, extramedullary disease, and aged 75 years or older. The ORR was 80.2% in the mezigdomide arm and 53.4% in the dexamethasone arm. Complete response or better was achieved in 26.7% and 8.9% of patients, respectively. 

Grade 3/4 treatment-emergent adverse events were observed in 83.7% of patients in the mezigdomide arm and 26.7% of patients in the dexamethasone arm, and most frequently included neutropenia and infections. Treatment-emergent infections resulted in 5 deaths in the mezigdomide arm and 2 deaths in the dexamethasone arm. Disease progression resulted in 62 deaths and 51 deaths, respectively.

“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 [R/R multiple myeloma] across multiple settings,” concluded Dr Richardson et al. 

Source: 

Richardson P, Fredrik Schjesvold F, Fu C, 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. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA7506.