Mezigdomide Plus Carfilzomib and Dexamethasone Improves PFS in R/R Multiple Myeloma

Key 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 end point was progression-free survival.
• Key Outcomes: The interim analysis demonstrated a statistically significant improvement in progression-free survival with the addition of mezigdomide. Safety findings were consistent with known profiles, with no new safety signals reported.
• Clinical Relevance: These results suggest that mezigdomide-based therapy may provide a new treatment option for patients with relapsed or refractory multiple myeloma. Ongoing follow-up will further clarify overall survival and long-term safety outcomes.

Interim results from the phase 3 SUCCESSOR-2 trial demonstrate that mezigdomide, a novel oral cereblon E3 ligase modulator, combined with carfilzomib and dexamethasone significantly improved progression-free survival (PFS) compared with carfilzomib and dexamethasone alone among patients with relapsed/refractory (R/R) multiple myeloma (MM).

In this multicenter, open-label study, 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 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