Unveiling the promising potential of luspatercept in transfusion-dependent lower-risk myelodysplastic syndromes: A systematic review and meta-analysis.

Abstract

e18580 Background: Myelodysplastic syndromes (MDS) are characterized by ineffective blood cell production. Luspatercept (Reblozyl) is a recently approved therapy for transfusion-dependent, lower-risk MDS patients who do not respond to erythropoietin-stimulating agents (ESAs). However, a comprehensive meta-analysis of its efficacy across available trials is lacking. This systematic review and meta-analysis aims to fill this gap by evaluating the efficacy of luspatercept in patients with MDS. Methods: We conducted a comprehensive search of PubMed, Embase, ClinicalTrials.gov, Cochrane Library, and Scopus from inception to date, adhering to PRISMA guidelines. After rigorously screening 3000 studies, we identified four relevant clinical trials involving 700 patients. Using R, we applied the inverse variance method to pool proportions, with a restricted maximum-likelihood estimator for tau² and the Q-profile method for confidence intervals of tau² and tau. We used a random-effects model to analyze untransformed proportions and performed sub-group analyses, estimating heterogeneity using I², Q statistics, and tau². Results: Our analysis revealed that 61% (95% CI: 47%-74%, I²=91%) of patients achieved Hematological Improvement Erythroid (HI-E) for at least 8 weeks. Nearly half (49%, 95% CI: 19%-80%, I²=97%) achieved transfusion independence for at least 8 weeks (TI ≥8). Subgroup analysis based on transfusion burden showed a higher prevalence of TI ≥8 in patients with low transfusion burden (LTD, <4 units per 8 weeks (78%, 95% CI: 68%-87%, I²=0%) compared to high transfusion burden (HTD, > four units per 8 weeks (21%, 95% CI: 15%-28%, I²=0%). Additionally, 53% (95% CI: 47%-59%, I²=0%) of patients had a hemoglobin improvement of ≥1 g/dl. Finally, 48% (95% CI: 9%-87%, I²=98%) achieved transfusion independence for at least 12 weeks (TI ≥12). Conclusions: This study demonstrates that luspatercept has promising potential for improving hematological outcomes in patients with MDS. Almost two-thirds achieved HI-E for at least 8 weeks, and nearly half became transfusion-independent for at least 12 weeks. Given the recent approval of luspatercept, further long-term studies with larger sample sizes are warranted to confirm these findings and comprehensively evaluate its long-term safety and efficacy profile.