Luspatercept Provides Safe, ‘Sustained Clinical Benefit’ in Patients with RS-Positive LR-MDS

By Melissa Badamo - Last Updated: November 1, 2023

Long-term luspatercept treatment of transfusion-dependent anemia in patients with ring sideroblast (RS)-positive lower-risk myelodysplastic syndromes (LR-MDS) provided “sustained clinical benefit with a predictable safety profile,” according to a study published in Leukemia.

The study also determined that red blood cell transfusion independence (RBC-TI) ≥8 weeks, RBC-TI ≥16 weeks, and/or an increase in hemoglobin ≥1.5 g/dl during the first 24 weeks of treatment was associated with improved overall survival (OS).

Led by Uwe Platzbecker, MD, of the University Hospital in Leipzig, this study is a long-term follow-up of the MEDALIST trial (NCT02631070) and presents “over two years of additional safety and efficacy data with concomitant impact on OS for MEDALIST trial patients.” The study includes pooled data from two data cutoffs: November 26, 2020 (MEDALIST final parent protocol data cutoff), and January 15, 2021 (long-term follow-up data cutoff).

MEDALIST, a phase III, double-blind, placebo-controlled trial, evaluated luspatercept treatment for anemia in adults with very low-, low-, or intermediate-risk RS-positive MDS according to the revised International Prognostic Scoring System, who were refractory, intolerant, or unlikely to respond to erythropoiesis-stimulating agents and were receiving regular RBC transfusions.

The MEDALIST trial randomized patients 2:1 into a luspatercept group (n=153) or a placebo group (n=76). Patients in the former group were given luspatercept 1.0 mg/kg up to 1.75 mg/kg every three weeks. A total of 48.4% of patients in the luspatercept cohort and 15.8% of placebo patients experienced RBC-TI ≥8 weeks, while 31.4% of patients receiving luspatercept and 7.9% of placebo patients experienced RBC-TI ≥16 weeks.

The primary endpoint was RBC-TI for ≥8 weeks during the first 24 weeks. Patients who continued to benefit from luspatercept following completion of the study were eligible for long-term follow-up and continued their prior dose and schedule regimen.

In the current analysis, the median cumulative duration of RBC-TI response with luspatercept treatment was 80.7 weeks. These data are consistent with the previous finding that 79% of MEDALIST primary endpoint responders experienced multiple separate response periods of RBC-TI ≥8 weeks.

“Taken together, these data demonstrate that patients continue to benefit from luspatercept beyond the first 24-week assessment period,” researchers concluded.


Platzbecker U, Santini V, Komrokji RS, et al. Long-term utilization and benefit of luspatercept in transfusion-dependent, erythropoiesis-stimulating agent-refractory or -intolerant patients with lower-risk myelodysplastic syndromes with ring sideroblasts. Leukemia. 2023. doi:10.1038/s41375-023-02031-7

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