BACKGROUND Patients with anemia and lower-risk myelodysplastic syndromes in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions. Luspatercept, a recombinant fusion protein that binds transforming growth factor β superfamily ligands to reduce SMAD2 and SMAD3 signaling, showed promising results in a phase 2 study. METHODS In a double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients with very-low-risk, low-risk, or intermediate-risk myelodysplastic syndromes (defined according to the Revised International Prognostic Scoring System) with ring sideroblasts who had been receiving regular red-cell transfusions to receive either luspatercept (at a dose of 1.0 up to 1.75 mg per kilogram of body weight) or placebo, administered subcutaneously every 3 weeks. The primary end point was transfusion independence for 8 weeks or longer during weeks 1 through 24, and the key secondary end point was transfusion independence for 12 weeks or longer, assessed during both weeks 1 through 24 and weeks 1 through 48. RESULTS Of the 229 patients enrolled, 153 were randomly assigned to receive luspatercept and 76 to receive placebo; the baseline characteristics of the patients were balanced. Transfusion independence for 8 weeks or longer was observed in 38% of the patients in the luspatercept group, as compared with 13% of those in the placebo group (P<0.001). A higher percentage of patients in the luspatercept group than in the placebo group met the key secondary end point (28% vs. 8% for weeks 1 through 24, and 33% vs. 12% for weeks 1 through 48; P<0.001 for both comparisons). The most common luspatercept-associated adverse events (of any grade) included fatigue, diarrhea, asthenia, nausea, and dizziness. The incidence of adverse events decreased over time. CONCLUSIONS Luspatercept reduced the severity of anemia in patients with lower-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red-cell transfusions and who had disease that was refractory to or unlikely to respond to erythropoiesis-stimulating agents or who had discontinued such agents owing to an adverse event. (Funded by Celgene and Acceleron Pharma; MEDALIST ClinicalTrials.gov number, NCT02631070; EudraCT number, 2015-003454-41.).

中文翻译：

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低风险骨髓增生异常综合征患者的Luspatercept。

背景技术贫血和低危骨髓增生异常综合征患者的红细胞生成刺激剂治疗无效，通常依赖于红细胞输血。Luspatercept是一种重组融合蛋白，可与转化生长因子β超家族配体结合以减少SMAD2和SMAD3信号传导，在2期研究中显示了令人鼓舞的结果。方法在一项双盲，安慰剂对照的3期临床试验中，我们随机分配了具有极低风险，低风险或中风险骨髓增生异常综合症（根据国际预后评分系统定义）的环铁粒母细胞患者接受常规红细胞输注的人每3周皮下注射一次接受luspatercept（每公斤体重1.0至1.75 mg的剂量）或安慰剂。主要终点是在1至24周内连续8周或更长时间的输血独立性，主要次要终点是在12至24周以及1至48周内连续12周或更长时间的输血独立性。结果229纳入研究的患者中，有153名被随机分配接受luspatercept，76名接受安慰剂。患者的基线特征是平衡的。在luspatercept组中，有38％的患者观察到8周或更长时间的输血独立性，而在安慰剂组中则为13％（P <0.001）。luspatercept组达到关键次要终点的患者比例高于安慰剂组（第1至24周分别为28％和8％，第1至48周分别为33％和12％； P <0.001两个比较）。最常见的与luspatercept相关的不良事件（任何级别）包括疲劳，腹泻，乏力，恶心和头晕。不良事件的发生率随时间下降。结论Luspatercept降低了患有环状铁粒母细胞的低风险骨髓增生异常综合症患者的贫血严重程度，这些患者已接受定期红细胞输注，且对促红细胞生成药物难治或不太可能发生反应或已停用此类药物由于不良事件。（由Celgene和Acceleron Pharma资助; MEDALIST ClinicalTrials.gov编号，NCT02631070; EudraCT编号，2015-003454-41。）结论Luspatercept降低了患有环状铁粒母细胞的低风险骨髓增生异常综合症患者的贫血严重程度，这些患者已接受定期红细胞输注，且对促红细胞生成药物难治或不太可能发生反应或已停用此类药物由于不良事件。（由Celgene和Acceleron Pharma资助; MEDALIST ClinicalTrials.gov编号，NCT02631070; EudraCT编号，2015-003454-41。）结论Luspatercept可降低患有环状铁粒母细胞的低危骨髓增生异常综合症患者的贫血严重程度，这些患者已接受定期红细胞输注，并且对促红细胞生成药物难治或不太可能发生反应，或已停用此类药物由于不良事件。（由Celgene和Acceleron Pharma资助; MEDALIST ClinicalTrials.gov编号，NCT02631070; EudraCT编号，2015-003454-41。）NCT02631070；EudraCT号，2015-003454-41。）。NCT02631070；EudraCT号，2015-003454-41。）。