Long-Term Updates From Phase 3 MEDALIST Trial

Long-Term Updates From Phase 3 MEDALIST Trial

The MEDALIST trial evaluated luspatercept in patients with lower-risk MDS who were red blood cell transfusion–dependent and largely refractory to ESAs. Patients were randomly assigned 2:1 to luspatercept or placebo, administered every 3 weeks, with the primary end point being transfusion independence for 8 weeks or more during weeks 1 to 24. Secondary end points included longer periods of transfusion independence and hematologic improvement. Recent long-term updates with a median follow-up of 39 months demonstrated durable efficacy. Nearly half of patients achieved at least 8 weeks of transfusion independence, with about one-third maintaining independence for 16 weeks or more. Among responders, the median duration of benefit extended beyond 1 year, with some achieving transfusion independence lasting over 2 years.

Safety data from extended follow-up remained reassuring. Grade 3-4 treatment-related adverse events occurred in under 10% of patients, most commonly fatigue and gastrointestinal adverse effects such as diarrhea. Roughly 15% of patients discontinued treatment due to adverse events. Cardiac events, including hypertension, were observed in approximately one-third of patients, but thromboembolic complications were rare and occurred at rates similar to placebo. The absence of new safety signals supports the long-term tolerability of luspatercept, although the cardiac events highlight the need for vigilant monitoring, especially in older patients with preexisting comorbidities.

Panelists discuss the clinical nuances of managing patients on luspatercept, particularly regarding variable periods of transfusion independence. They emphasize the importance of distinguishing true loss of response from transient setbacks caused by stressors such as infections or hospitalizations, noting that rechallenging luspatercept may recapture benefit in some cases. Debate also centers on cardiovascular management in this older population. The experts recommend close collaboration with primary care and cardiology departments, proactive blood pressure control, and individualized use of preventive strategies such as aspirin, balancing cardiovascular risk with bleeding concerns. Importantly, as survival improves for patients with lower-risk MDS, optimization of comorbid conditions and holistic patient care become increasingly critical alongside disease-directed therapy.