Mezigdomide Plus Carfilzomib and Dexamethasone Significantly Improves Progression-Free Survival in Relapsed or Refractory Multiple Myeloma

Clinical Summary: 

• Design/Population: The phase 3 SUCCESSOR-2 trial randomized patients with relapsed or refractory multiple myeloma to receive mezigdomide plus carfilzomib and dexamethasone or carfilzomib and dexamethasone alone. The primary endpoint was progression-free survival.
• Key Outcomes: Interim analysis demonstrated a statistically significant and clinically meaningful improvement in progression-free survival with the addition of mezigdomide. The combination showed a safety profile consistent with the known toxicities of the individual agents, with no new safety signals observed.
• Clinical Relevance: These findings support mezigdomide plus carfilzomib and dexamethasone as a potential new treatment option for patients with relapsed or refractory multiple myeloma.

Interim results from the phase 3 SUCCESSOR-2 trial showed that adding mezigdomide, an oral cereblon E3 ligase modulator, to carfilzomib and dexamethasone significantly improved progression-free survival (PFS) compared with carfilzomib and dexamethasone alone in patients with relapsed or refractory multiple myeloma.

In this multicenter, open-label trial, patients were randomized to receive either mezigdomide plus carfilzomib and dexamethasone or carfilzomib and dexamethasone alone. The phase 3 primary end point was PFS. Key secondary end points included overall survival (OS), overall response rate (ORR), duration of response, time to progression, time to next treatment, minimal residual disease (MRD) negativity, and health-related quality of life.

At interim analysis, mezigdomide plus carfilzomib and dexamethasone demonstrated a statistically significant and clinically meaningful improvement in PFS compared with carfilzomib and dexamethasone alone. Safety findings were consistent with the known safety profiles of mezigdomide and the combination regimen. No new safety signals were identified.

“While treatment advances have been meaningful, far too many patients with multiple myeloma still relapse or stop responding—making the need for new options urgent,” said Paul Richardson, MD, Dana-Farber Cancer Institute, Boston, Massachusetts.  “These data underscore the potential of [mezigdomide plus carfilzomib and dexamethasone] as an oral regimen that could address a key unmet need for patients previously exposed to anti-CD38 and lenalidomide.”

Investigators plan to present the full data from this phase 3 trial at a future medical meeting. 

Source: 

Bristol Myers Squibb. Bristol Myers Squibb announces positive phase 3 results from the SUCCESSOR-2 study of oral mezigdomide in relapsed or refractory multiple myeloma. Accessed on March 10, 2026. https://news.bms.com/news/corporate-financial/2026/Bristol-Myers-Squibb-Announces-Positive-Phase-3-Results-from-the-SUCCESSOR-2-Study-of-Oral-Mezigdomide-in-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx