A Systematic Review and Meta-Analysis of Luspatercept for Anemia Treatment in Low Risk Myelodysplastic Syndrome with Ring Sideroblast Subtype in Phase II and Phase III Clinical Trials

Background: Low-risk Myelodysplastic Syndromes (MDS) patients commonly present with anemia and may become blood transfusions dependent upon progression. Luspatercept, a targeted drug for an activin receptor ligand has emerged as new anemia treatment in MDS for patients with ring sideroblasts and the patients with SF3B1 mutation. This systemic review highlights the efficacy of luspatercept in MDS patients whom erythropoietin stimulating agents (ESA) are not effective. Methods: We conducted a comprehensive literature search using PubMed, Clinical trial.gov, Embase, Cochrane, and Web of science. Our search strategy included MeSH (Medical Subject Headings) terms and keywords for MDS and luspatercept including trade names and generic names from inception to 29 April 2020. Studies were selected according to PRISMA guidelines. The initial screening revealed 240 articles. After excluding review articles, duplicates, and non-relevant articles, finally we included two clinical trials, which reported transfusion independence (TI), an erythroid response (HI-E) in MDS patients with luspatercept. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.0.2) to report the efficacy of luspatercept. We pooled the results of the experimental arms of the two trials using the inverse variance method and logit transformation. Between studies, variance was calculated using DerSimonian-Laird Estimator. Results: A total of 287 patients were enrolled and evaluated in two phases II/III trials. Platzbecker et al and Fenaux et al reported Erythropoietin stimulating agents (ESA) with one median prior line of therapy (n= 148, n=46). Fenaux et al. also reported iron chelation therapy (n=71) as a prior line of therapy. Patients having ring sideroblast positive