Luspatercept for patients with lower-risk myelodysplastic syndromes/neoplasms: a systematic review and meta-analysis

Abstract

Luspatercept has emerged as a novel therapy for anemia in transfusion-dependent (TD) lower-risk myelodysplastic syndromes (LR-MDS). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of luspatercept in TD LR-MDS. Six databases were searched through March 2025 to find relevant material. Studies were screened and extracted by 2 independent authors. A total of 20 studies encompassing 3455 patients were included in the analysis. The pooled 8-week transfusion independence (TI) rate was 51.2% (95% confidence interval [CI], 39.9-60.4; I2 = 94.9%), with higher rates observed among ring sideroblast–positive (RS+) patients (57.8%; 95% CI, 47.4-67.7; I2 = 86%) and those with low transfusion burden (LTB; 72.9%; 95% CI, 60.4-82.6; I2 = 0%). The 12-week and 24-week TI rates were 57.0% (95% CI, 48.1-65.5; I2 = 90%) and 35.8% (95% CI, 28.7-43.6; I2 = 82.1%), respectively. Hematologic improvement–erythroid was achieved in 51.3% of patients (95% CI, 41.3%–61.2%; I2 = 93%). The most frequent adverse events were peripheral edema (17.8%; 95% CI, 11.4-26.8), diarrhea (15.6%; 95% CI, 8.2-27.7), and fatigue (11.4%; 95% CI, 5.4-22.6). Serious adverse events occurred in 28.0% of patients (95% CI, 12.8-50.7; I2 = 97.2%). Luspatercept is an effective and well-tolerated treatment for anemia in TD LR-MDS, especially in patients with RS+ and LTB. Its favorable safety profile and high TI rates, particularly in erythropoiesis-stimulating agent–naïve populations, support its use in the frontline setting.