A Novel Insight Into Luspatercept: Therapeutic Implications in Myelodysplastic Syndrome Patients With Elevated Pulmonary Artery Systolic Pressure

ABSTRACT

Luspatercept enhances late‐stage erythroid maturation by sequestering transforming growth factor‐β superfamily ligands and attenuating pathological signaling, with a mechanism highly analogous to that of sotatercept, a breakthrough therapeutic agent for pulmonary hypertension (PH). Despite this solid mechanistic basis, the potential vascular and prognostic effects of luspatercept in PH patients remain largely uncharacterized. This retrospective proof‐of‐concept study aimed to evaluate the impact of luspatercept on pulmonary artery pressure and surrogate prognostic markers, and to explore its novel therapeutic potential in patients with increased pulmonary artery systolic pressure (PASP). We retrospectively analyzed serial echocardiographic parameters among patients with myelodysplastic syndrome (MDS) who received luspatercept treatment, focusing on individuals with elevated baseline PASP. Dynamic changes in cardiopulmonary indicators and laboratory biomarkers were comprehensively compared before and after intervention. A total of five MDS patients with elevated baseline PASP were enrolled in the final analysis. Although formal statistical comparisons failed to reach significance, which was largely attributable to the limited sample size, consistent clinically beneficial improvements were observed after luspatercept treatment. The median PASP decreased from 62.0 (IQR 14) mmHg at baseline to 33.0 (IQR 18.5) mmHg following treatment. Parallel reductions in N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and uric acid levels were identified, accompanied by a mild yet favorable elevation in hemoglobin concentration. In this small cohort of MDS patients with elevated PASP, luspatercept treatment was associated with decreased pulmonary artery pressure, reduced NT‐proBNP and uric acid levels, and improved hemoglobin levels. These preliminary findings suggest novel pleiotropic benefits of luspatercept in improving pulmonary arterial pressure, cardiac function, and anemia status, providing a compelling rationale for further prospective clinical studies to verify its therapeutic value in PH populations.