Real-World Data Support Luspatercept vs ESAs for Anemia in Lower-Risk MDS

First-line luspatercept may offer significant advantages over erythropoiesis-stimulating agents (ESAs) for anemia in patients with lower-risk myelodysplastic syndromes (LR-MDS), according to a real-world study presented at the 2025 American Society of Clinical Oncology annual meeting.1

The study, which evaluated interim data from an ongoing retrospective review of medical records, supports earlier clinical trial findings of luspatercept’s efficacy. The FDA approved luspatercept in August 2023 based on findings from the COMMANDS trial (NCT03682536), in which 58.5% of patients with LR-MDS at risk of anemia were able to forego transfusions for 12 weeks vs 31.2% of patients receiving an ESA.2

The findings support the use of luspatercept as the first-line standard of care for anemia treatment in patients with MDS. | Image Credit: wanchalerm - stock.adobe.com

"LR-MDS patients receiving ESAs for anemia often experience treatment resistance or relapse," the authors wrote.1 "Evidence from the COMMANDS trial led to luspatercept’s US FDA approval in August 2023 as first-line treatment for anemia in patients with LR-MDS. This is the first study assessing real-world characteristics and outcomes in patients with LR-MDS receiving first-line luspatercept or ESA after first-line luspatercept approval."

First-line treatment for anemia in patients with MDS has traditionally relied on ESAs, such as epoetin alfa or darbepoetin, which stimulate red blood cell production.3 Luspatercept, a recombinant fusion protein, enhances late-stage erythropoiesis.

The new real-world analysis included 103 patients with LR-MDS based on International Prognostic Scoring System (IPSS) or revised IPSS (IPSS-R) criteria who received either luspatercept (n = 46) or ESAs (n = 57) as first-line therapy between August 2023 and July 2024. Patient data were retrospectively reviewed between October and December 2024.

At a median follow-up of 7.9 months in the luspatercept cohort and 8.4 months in the ESA cohort, 89.1% of patients receiving luspatercept experienced a hemoglobin increase of at least 1.5 g/dL within the first 6 months, compared with 56.1% in the ESA group. Sustained improvement, defined as a 1.5 g/dL or greater hemoglobin increase maintained for at least 8 weeks, was also more common in the luspatercept group (80.4% vs 47.4%).

Patients in the luspatercept cohort also experienced faster and more sustained red blood cell transfusion independence. Among those who were transfusion-dependent at baseline, 91.7% of luspatercept-treated patients were transfusion independent within the 3 months vs 71.4% in the ESA group. Patients receiving luspatercept also reached independence more quickly, with a median of 0.8 months vs 1.9 months in the ESA group, and were more likely to remain transfusion independent for at least 12 weeks (91.7% vs 64.3%).

The study also showed a greater mean hemoglobin gain over 6 months in the luspatercept cohort vs the ESA cohort (1.7 g/dL vs 1.0 g/dL, respectively) and a greater proportion of patients whose transfusion needs reduced by 50% or more (75% vs 42.9%).

"During the first 6 months of treatment, a higher proportion of patients receiving first-line luspatercept showed improvement in [hemoglobin] and a reduced need for RBC compared to those receiving first-line ESA," the authors concluded. "This analysis corroborates the results of the COMMANDS trial and demonstrates the favorable real-world effectiveness of first-line luspatercept vs first-line ESA for anemia treatment in LR-MDS."

The findings support the use of luspatercept as the first-line standard of care for anemia treatment in patients with MDS, the authors wrote. They also inform real-world anemia management in patients with LR-MDS in routine clinical practice.

References

1. Amanam IU, Agu C, Korgaonkar S, et al. Real-world (RW) outcomes of patients (pts) with lower-risk myelodysplastic syndrome (LR-MDS) receiving first-line (1L) luspatercept (LUSPA) or 1L erythropoiesis-stimulating agents (ESA) in the US. J Clin Oncol. 2025;43(suppl 17):Abstract 6570. doi:10.1200/JCO.2025.43.16_suppl.6570

2. Munz K. FDA approves luspatercept as first-line anemia treatment in patients with lower-risk MDS. AJMC®. August 29, 2023. Accessed June 4, 2025. https://www.ajmc.com/view/fda-approves-luspatercept-as-first-line-anemia-treatment-in-patients-with-lower-risk-mds

3. Meunier M, Park S. Lower-risk myelodysplastic syndromes: Current treatment options for anemia. EJHaem. 2022;3(4):1091-1099. doi:10.1002/jha2.523