Luspatercept in patients with lower-risk myelodysplastic syndromes (MDS): A systematic review and meta-analysis.

Abstract

e18574 Background: Myelodysplastic syndromes (MDS) are bone marrow disorders often leading to anemia and transfusion dependence (TD). Luspatercept (Lusp) has shown promise in reducing transfusion needs in lower-risk (LR)-MDS patients (pts). This study evaluates the efficacy and safety of Lusp for transfusion-dependent MDS pts. Methods: A systematic review and meta-analysis was conducted (CRD42024574093). Studies published prior to 8/2024 were identified through six databases. Two independent reviewers assessed studies against inclusion and exclusion criteria. The risk of bias was assessed using the Cochran and Downs & Black quality assessment checklists. A random-effects model was used to pool outcomes, and heterogeneity was measured using the I² statistic. Finally, dedicated subgroup analyses were conducted. Results: A total of 693 studies were identified, from which 13 were included, that have 3 clinical trials and 10 cohort studies. These studies collectively included 2,614 pts, from those, 2331 received Lusp, and 1478 were TD before starting treatment. The quality assessment revealed that 6 studies were rated excellent, 3 good, 2 fair, and 1 poor. The results demonstrated the efficacy of Lusp in achieving TI at both 8 and 12 weeks (52.2% and 45.6%, respectively), with a well-tolerated safety profile (Table). The Quality of Adjusted Life Year during Lusp treatment for ESA-refractory pts was 0.721. No statistically significant publication bias was observed regarding any of the study's primary endpoints. Conclusions: The study findings support the use of Lusp, particularly in frontline settings for LR-MDS pts with Ring Sideroblasts. Lusp demonstrated responses in ESA-resistant populations. Baseline Characteristics n K Age (mean) 2614 12 73.5 years Sex (male) 2614 12 57.7% IPSS-R (Very low/Low) 565 5 75.9% SF3B1 617 5 53.7% Outcome n K Pooled Percentage (95% CI; I²) TI at 8 weeks L1&RS+ Refractory to ESA/RS+ Refractory to ESA/RS- Refractory to Lusp/ESA or HTB 1445450443365184 104333 52.2 (39.1 – 65.0; 95%)80.7 (72.7 – 86.9; 65%)42.8 (25.9 – 61.6; 95%)45.2 (33.0 – 57.9; 87%)29.9 (19.8 – 42.3; 74%) TI at 12 weeks L1&RS+ Refractory to ESA/RS+ Refractory to ESA/RS- 809189261321 5222 45.6 (31.7 – 60.2; 95%)67.7 (60.7 – 74.0; 0%)45.9 (32.8 – 59.6; 84%)37.2 (26.1 – 49.8; 90%) Acute Myeloid Leukemia transformation 536 3 2.6 (1.5 – 4.3; 0%) Serious Adverse Events 1058 4 28.1 (13.6 – 49.2; 98%) Peripheral edema 335 2 18.8 (12.8 – 26.6; 81%) Fatigue 443 3 16.8 (8.6 – 30.2; 90%) Back pain 335 2 16.1 (10.8 – 23.2; 79%) Diarrhea 443 3 14.5 (6.0 – 31.0; 90%) Dizziness 418 3 12.4 (6.1 – 23.5; 85%) n: Number of pts; K: number of studies; TI: Transfusion Independence; CI: Confidence Interval; L1: Frontline Setting; RS: Ring Sideroblasts; ESA: Erythropoiesis-Stimulating Agents; Lusp: Luspatercept; HTB: High Transfusion Burden; Refractory: Not responding to or resistant to treatment; I²: Measure of heterogeneity.