Luspatercept for Patients with Lower-Risk Myelodysplastic Syndromes/Neoplasms: A Systematic Review and Meta-Analysis Open Access

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 aims to evaluate the efficacy and safety of luspatercept in LR-MDS. We conducted a systematic review and meta-analysis 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 two independent authors. A total of 20 studies encompassing 3,455 patients were included in the analysis. The pooled 8-week transfusion independence (TI) rate was 51.2% (95% CI: 39.9%-60.4%; I² = 94.9%), with higher rates observed among 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 RS⁺ and LTB patients. Its favorable safety profile and higher TI rates, particularly in ESA-naïve populations supports its use in the frontline setting.