EFFICACY AND SAFETY OF LUSPATERCEPT IN MYELODYSPLASTIC SYNDROME/NEOPLASM WITH VERY LOW/LOW/INTERMEDIATE RISK REQUIRED TRANSFUSION: A SYSTEMATIC REVIEW AND SINGLEARM META-ANALYSIS

Abstract

Objective: Myelodysplastic syndrome (MDS) and myeloid neoplasms are hematological disorders characterized by abnormal blood cell production. Patients with very low, low, or intermediate-risk MDS/neoplasms often require regular red blood cell (RBC) transfusions to manage anemia. Luspatercept has been evaluated in several retrospective studies and randomized controlled trials as a promising treatment. However, the results of these studies have shown some discrepancies. Therefore, we conducted a systematic review and a single-arm meta-analysis to consolidate the current evidence on the efficacy and safety of luspatercept in the treatment of patients with very low, low, or intermediate-risk MDS/neoplasms who require regular RBC transfusions. Methods: Following PRISMA guidelines, we performed a systematic literature review and a meta-analysis. Our search strategy encompassed PubMed, Embase, and Cochrane Library databases, utilizing the key terms ’luspatercept’, ’myelodysplastic syndrome’. Efficacy outcomes included achieving transfusion independence for at least 8 weeks or longer (TI≥8) and hematological improvement-erythroid (HI-E) response as defined by the IWG 2006 criteria. Safety outcomes comprised adverse events. Data were summarized using pooled mean for continuous outcomes and pooled proportion for dichotomous outcomes, with 95% confidence intervals. I2 was used to assess heterogeneity. Statistical analyses were performed using R software, version 4.3.2. Results: Out of 940 initially identified studies, 11 were included in the final analysis, comprising a total of 1,069 patients. All patients required regular red blood cell transfusions. The follow-up periods were not specified. The mean age and gender distribution of patients were not mentioned in the given text. The pooled proportion for (TI≥8) was 40.5% (95% CI: 25.49-55.5%; I2 = 98%). The pooled proportion for (HI-E) response was 47.27% (95% CI: 35.21-59.33%; I2 = 90%), In the subgroup analysis, the prevalence of TI≥8 in the RCT group was 51.31% (95% CI: 25.14-77.47%; I2 = 96%), while in the real-world group, it was 28.10% (95% CI: 15.81-40.38, I2 = 81%). Most common AEs by pooled proportion were: gastrointestinal disorders, 11.07% (95% CI, 2.0-20.14%; I2 = 95%); fatigue, 8.85% (95% CI: 3.56-14.15%; I2 = 90%); cardiac events, 8.94% (95% CI: 4.57-13.31%; I2 = 88%); and nervous system disorders, 6.84% (95% CI: 1.43-12.24%; I2 = 86%). Discussion: Luspatercept demonstrated significant benefits in achieving transfusion independence and improving erythroid response, especially in patients for whom traditional stimulating agents were ineffective. However, real-world data indicated lower success rates compared to RCTs, likely due to treatment discontinuation and previous multiple drug use. Common adverse events included fatigue and nervous system, gastrointestinal and cardiac disorders. Despite limitations such as high heterogeneity and small sample sizes in some studies, Luspatercept's favorable safety profile and substantial benefits support its use in MDS patient management. Conclusion: This meta-analysis demonstrates Luspatercept's efficacy and safety in treating transfusion-dependent MDS patients with lower-risk disease. However, significant heterogeneity and differences between RCTs and real-world data necessitate cautious interpretation. Further prospective studies are needed to strengthen the evidence and fully assess Luspatercept's efficacy and safety profile.