The medical journal The Lancet has published interim analysis data from the SUCCESSOR-2 trial, which were presented at the 2026 American Society of Clinical Oncology (ASCO) and the 2026 European Hematology Association (EHA) annual meetings.
As more patients with multiple myeloma receive lenalidomide and anti-CD38 monoclonal antibodies as part of their initial treatment, finding effective options at first relapse has become increasingly challenging. The phase III SUCCESSOR-2 study investigated whether adding mezigdomide—a next-generation cereblon E3 ligase modulator (CELMoD)—to carfilzomib and dexamethasone could improve outcomes compared with carfilzomib and dexamethasone alone.
The study enrolled patients whose myeloma had returned after at least one prior line of therapy and who had previously been treated with both lenalidomide and an anti-CD38 antibody. Most participants had disease that was refractory to these therapies, representing a growing group of patients with significant unmet medical needs.
Researchers found that the three-drug combination of mezigdomide, carfilzomib, and dexamethasone nearly doubled median progression-free survival compared with carfilzomib and dexamethasone alone (18.0 months versus 8.3 months). This means patients receiving the mezigdomide-based regimen were able to live significantly longer without their disease worsening.
While the combination was associated with higher rates of serious side effects—including infections and low white blood cell counts—most adverse events were manageable with supportive care and standard clinical practices.
Why This Study Matters
The treatment landscape for multiple myeloma is rapidly evolving. As patients receive more effective therapies earlier in their disease course, physicians need new options when those treatments stop working. The SUCCESSOR-2 results suggest that mezigdomide may help fill this gap, particularly for patients whose disease has become resistant to both lenalidomide and anti-CD38 therapies.
Importantly, the study demonstrated a substantial improvement in progression-free survival in a patient population that often has limited treatment choices. These findings support mezigdomide-based therapy as a potentially meaningful option as early as first relapse and highlight the continued development of next-generation immune-modulating therapies in myeloma.
To learn more about the study design, patient population, efficacy results, and safety findings, review the full publication.