Mezigdomide Regimen Boosts PFS in Relapsed/Refractory Multiple Myeloma

Combining oral mezigdomide with carfilzomib (Kyprolis) and dexamethasone demonstrated a statistically significant and clinically meaningful progression-free survival (PFS) improvement vs carfilzomib/dexamethasone alone among patients with relapsed/refractory multiple myeloma, according to a press release on findings from the phase 3 portion of the SUCCESSOR-2 trial (NCT05552976).¹

The safety data revealed that the profile of mezigdomide was comparable with prior reports of the agent and other components of the combination. Investigators will continue to follow patients for safety and survival.

Developers look to share detailed results from the SUCCESSOR-2 trial at a future medical meeting and discuss their findings with regulatory health authorities.

“It is important for patients to have treatment options that offer enduring disease control. These positive interim data show that adding mezigdomide, a cereblon E3 ligase modulator [CELMoD] specifically optimized for enhanced myeloma cell killing and immune activation compared with immunomodulatory drug [IMiD] agents, to carfilzomib and dexamethasone may provide clinical benefit in earlier relapse,” Meletios-A. (Thanos) Dimopoulos, MD, professor and chairman in the Department of Clinical Therapeutics at Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, stated in the press release.¹

Investigators of the open-label, multicenter phase 2/3 SUCCESSOR-2 trial assessed the safety and efficacy of mezigdomide plus carfilzomib and dexamethasone compared with carfilzomib/dexamethasone alone among those with relapsed/refractory multiple myeloma. The trial’s primary end point was PFS. Secondary end points included overall survival, overall response rate, duration of response, time to progression, time to next treatment, minimal residual disease negativity, and health-related quality of life (HRQOL). HRQOL outcomes were based on changes from baseline in the European Organization for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) and the EORTC Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20).²

Patients 18 years and older with a documented diagnosis of multiple myeloma and measurable disease, marked by an M-protein of at least 0.5 g/dL by serum protein electrophoresis or an M-protein of at least 200 mg per 24-hour urine collection based on urine protein electrophoresis were eligible for enrollment on the trial. If patients did not have measurable disease, a serum free light chain level of more than 100 mg/L involved light chain and an abnormal κ/λ free light chain ratio were required for study entry. Other eligibility criteria included having 1 or more prior lines of anti-myeloma treatment, prior treatment with lenalidomide (Revlimid) plus 2 or more cycles of an anti-CD38 monoclonal antibody, minimal response or better to at least 1 prior anti-myeloma treatment, and documented disease progression on or after the most recent anti-myeloma regimen.

Those with prior treatment with mezigdomide or carfilzomib and prior receipt of allogeneic stem cell transplant at any time or autologous stem cell transplant within 12 weeks of beginning study treatment were ineligible for enrollment on the trial.

“We are excited by these results, which underscore Bristol Myers Squibb’s leadership in treating multiple myeloma and our unwavering commitment to patients living with this persistent and challenging disease,” Cristian Massacesi, executive vice president, chief medical officer, and head of development at Bristol Myers Squibb, the developer of mezigdomide, said in the press release.¹ “Importantly, these findings reinforce the value of our CELMoD program and our targeted protein degradation platform, and strengthen our confidence in bringing forward effective, accessible oral treatment options for patients with difficult-to-treat blood cancers and potentially beyond.”

References

1. Bristol Myers Squibb announces positive phase 3 results from the SUCCESSOR-2 study of oral mezigdomide in relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb. March 9, 2026. Accessed March 9, 2026. https://tinyurl.com/nc2m7cj4
2. A study to evaluate mezigdomide in combination with carfilzomib and dexamethasone (MeziKD) versus carfilzomib and dexamethasone (Kd) in participants with relapsed or refractory multiple myeloma (SUCCESSOR-2) (SUCCESSOR-2). ClinicalTrials.gov. Updated February 11, 2026. Accessed March 9, 2026. https://tinyurl.com/yn74ajkn