Bristol Myers Squibb reported positive Phase 3 SUCCESSOR-2 results showing mezigdomide reduced the risk of progression or death by 52% and doubled progression-free survival in relapsed or refractory multiple myeloma.
Written By: Sana Khan, BPharm
Reviewed By: Pharmacally Editorial Team
Bristol Myers Squibb announced positive late-breaking Phase 3 results from the SUCCESSOR-2 trial evaluating mezigdomide in combination with carfilzomib and dexamethasone (MeziKd) in patients with relapsed or refractory multiple myeloma (RRMM).
Presented at the 2026 ASCO Annual Meeting, the regimen achieved a median progression-free survival (PFS) of 18.0 months versus 8.3 months with carfilzomib and dexamethasone (Kd) alone, translating to a 52% reduction in the risk of disease progression or death (HR 0.48; p<0.0001).
The results mark the first Phase 3 success for mezigdomide and provide important validation for Bristol Myers Squibb’s cereblon-targeting protein degradation platform.
CELMoD Mechanism Targets Resistance
Mezigdomide is an oral cereblon E3 ligase modulator (CELMoD) that induces rapid degradation of the transcription factors Ikaros and Aiolos. This dual mechanism enhances direct myeloma cell killing while stimulating immune activity, offering a differentiated approach for patients whose disease has become resistant to standard therapies.
Multiple myeloma remains an incurable blood cancer characterized by repeated relapses and increasing treatment resistance. Outcomes often worsen with each successive line of therapy, underscoring the need for effective options after early relapse.
Broad Efficacy Across Patient Subgroups
SUCCESSOR-2 (NCT05552976) enrolled 479 patients with a median of two prior lines of therapy. More than 92% of participants were triple-class exposed, reflecting the increasingly complex treatment landscape in relapsed disease. Notably, 85.8% of patients were refractory to an anti-CD38 monoclonal antibody and 75.8% were refractory to lenalidomide.
MeziKd achieved an overall response rate (ORR) of 80.2% compared with 53.4% for Kd, while complete response or better was observed in 26.7% versus 8.9% of patients, respectively. PFS benefit was observed across key predefined subgroups, including patients treated in second- and third-line settings, those with high-risk cytogenetics, and patients previously exposed to anti-CD38 antibodies.
Median overall survival had not yet been reached at the time of analysis, while duration-of-response findings suggested sustained clinical benefit among responders.
Safety Profile Remains Manageable
The safety profile of MeziKd was consistent with previous mezigdomide studies. Grade 3 or 4 treatment-emergent adverse events occurred in 83.7% of patients receiving MeziKd compared with 56.5% in the Kd arm.
Neutropenia and infections were the most notable Grade 3/4 toxicities, occurring more frequently with MeziKd. Despite higher rates of hematologic toxicity, adverse events were generally manageable within the known safety profile of the regimen.
Expert Commentary Highlights Clinical Impact
Paul Richardson, MD, of Dana-Farber Cancer Institute, highlighted the significance of achieving 18 months of disease control in a heavily pretreated population where durable responses become increasingly difficult with each relapse. He noted that the results reinforce the potential role of MeziKd across multiple treatment settings.
Cristian Massacesi, MD, executive vice president, chief medical officer and head of development at Bristol Myers Squibb, said the findings validate cereblon as a critical therapeutic target in multiple myeloma and further support the company’s targeted protein degradation strategy.
Regulatory Outlook and Next Steps
Bristol Myers Squibb plans to submit the SUCCESSOR-2 data to global health authorities to support future regulatory discussions. The company is also advancing mezigdomide in additional Phase 3 studies, including the ongoing SUCCESSOR-1 trial.
If approved, mezigdomide could establish the first Phase 3-validated CELMoD regimen for relapsed or refractory multiple myeloma and expand treatment options for patients whose disease has progressed after current standards of care.
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About the Writer
Sana Jamil Khan (LinkedIn) is a B. Pharm graduate with a strong interest in medical writing and scientific communication. Her work focuses on interpreting clinical research, exploring developments in pharmaceutical science, and presenting complex medical information in a clear and accessible manner. She is particularly interested in topics related to human clinical studies, drug safety observations, and emerging therapeutic research.