The preplanned interim analysis of the COMMANDS trial showed greater efficacy of luspatercept than epoetin alfa for treating anaemia in erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. In this Article, we report the results of the primary analysis of the trial. COMMANDS is a phase 3, open-label, randomised, controlled trial conducted at 142 sites in 26 countries. Eligible patients were those aged 18 years or older, with myelodysplastic syndromes of very low risk, low risk, or intermediate risk (as defined by the Revised International Prognostic Scoring System), who were ESA-naive and transfusion dependent, and had a serum erythropoietin concentration of less than 500 U/L. Patients were stratified by baseline red blood cell transfusion burden, serum erythropoietin concentration, and ring sideroblast status, and randomly allocated (1:1) to receive luspatercept (1·0–1·75 mg/kg body weight, subcutaneously, once every 3 weeks) or epoetin alfa (450–1050 IU/kg body weight, subcutaneously, once a week; maximum total dose 80 000 IU) for at least 24 weeks. The primary endpoint was red blood cell transfusion independence lasting at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1–24), evaluated in the intention-to-treat population. The safety population included all patients who received at least one dose of treatment. This trial is registered with (; active, not recruiting). Between Jan 2, 2019, and Sept 29, 2022, 363 patients were screened and randomly allocated: 182 (50%) to luspatercept and 181 (50%) to epoetin alfa. Median age was 74 years (IQR 69–80), 162 (45%) patients were female, and 201 (55%) were male. 289 (80%) were White, 44 (12%) were Asian, and two (1%) were Black or African American. 23 (6%) were Hispanic or Latino and 311 (86%) were not Hispanic or Latino. Median follow-up for the primary endpoint was 17·2 months (10·4–27·7) for the luspatercept group and 16·9 months (10·1–26·6) for the epoetin alfa group. A significantly greater proportion of patients in the luspatercept group reached the primary endpoint (110 [60%] 63 [35%]; common risk difference on response rate 25·4% [95% CI 15·8–35·0]; p<0·0001). Median follow-up for safety analyses was 21·4 months (IQR 14·2–32·4) for the luspatercept group and 20·3 months (12·7–30·9) for the epoetin alfa group. Common grade 3–4 treatment-emergent adverse events occurring among luspatercept recipients (n=182) were hypertension (19 [10%] patients), anaemia (18 [10%]), pneumonia (ten [5%]), syncope (ten [5%]), neutropenia (nine [5%]), thrombocytopenia (eight [4%]), dyspnoea (eight [4%]), and myelodysplastic syndromes (six [3%]); and among epoetin alfa recipients (n=179) were anaemia (14 [8%]), pneumonia (14 [8%]), neutropenia (11 [6%]), myelodysplastic syndromes (ten [6%]), hypertension (eight [4%]), iron overload (seven [4%]), and COVID-19 pneumonia (six [3%]). The most common serious treatment-emergent adverse events in both groups were pneumonia (nine [5%] luspatercept recipients and 13 [7%] epoetin alfa recipients) and COVID-19 (eight [4%] luspatercept recipients and ten [6%] epoetin alfa recipients). One death (due to acute myeloid leukaemia) considered to be luspatercept-related was reported at the interim analysis. Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. Significantly more patients had red blood cell transfusion independence and haematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups. Celgene and Acceleron Pharma.

中文翻译：

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Luspatercept 与 epoetin alfa 在未使用红细胞生成刺激剂、输血依赖性、低风险骨髓增生异常综合征 (COMMANDS) 中的比较：一项 3 期、开放标签、随机、对照试验的初步分析


COMMANDS 试验的预先计划中期分析显示，对于未接受红细胞生成刺激剂 (ESA) 的输血依赖性、低风险骨髓增生异常综合征患者的贫血治疗，luspatercept 比阿法依泊汀 (epoetin alfa) 更有效。在本文中，我们报告了试验的初步分析结果。 COMMANDS 是一项 3 期、开放标签、随机对照试验，在 26 个国家的 142 个地点进行。符合条件的患者是年龄 18 岁或以上、患有极低风险、低风险或中等风险（根据修订的国际预后评分系统定义）的骨髓增生异常综合征、未接受过 ESA 且依赖输血且血清促红细胞生成素检测结果的患者。浓度小于500 U/L。根据基线红细胞输注负担、血清促红细胞生成素浓度和环状铁粒幼细胞状态对患者进行分层，并随机分配（1:1）接受luspatercept（1·0–1·75 mg/kg体重，皮下注射，每3次）周）或阿法依泊汀（450-1050 IU/kg 体重，皮下注射，每周一次；最大总剂量 80 000 IU）至少 24 周。主要终点是持续至少 12 周的红细胞输注独立性，同时平均血红蛋白增加至少 1·5 g/dL（第 1-24 周），在意向治疗人群中进行评估。安全人群包括接受至少一剂治疗的所有患者。该试验已注册（；活跃，未招募）。 2019年1月2日至2022年9月29日期间，对363名患者进行了筛查并随机分配：182名患者（50%）接受luspatercept治疗，181名患者（50%）接受阿法依泊汀治疗。中位年龄为 74 岁（IQR 69-80），162 名患者（45%）为女性，201 名患者（55%）为男性。 289 名（80%）是白人，44 名（12%）是亚裔，两名（1%）是黑人或非裔美国人。 23 人 (6%) 是西班牙裔或拉丁裔，311 人 (86%) 不是西班牙裔或拉丁裔。 luspatercept 组主要终点的中位随访时间为 17·2 个月 (10·4–27·7)，而阿法依泊汀组为 16·9 个月 (10·1–26·6)。 luspatercept 组中达到主要终点的患者比例显着增加（110 [60%] 63 [35%]；缓解率的常见风险差异为 25·4% [95% CI 15·8–35·0]；p <0·0001）。 luspatercept 组的安全性分析中位随访时间为 21·4 个月（IQR 14·2–32·4），而阿法依泊汀组为 20·3 个月（12·7–30·9）。 luspatercept 接受者 (n=182) 中发生的常见 3-4 级治疗引起的不良事件包括高血压（19 例 [10%] 患者）、贫血（18 例 [10%]）、肺炎（10 例 [5%]）、晕厥（ 10 例 [5%]）、中性粒细胞减少症（9 例 [5%]）、血小板减少症（8 例 [4%]）、呼吸困难（8 例 [4%]）和骨髓增生异常综合征（6 例 [3%]）；阿尔法依泊汀接受者 (n=179) 中出现贫血 (14 [8%])、肺炎 (14 [8%])、中性粒细胞减少症 (11 [6%])、骨髓增生异常综合征 (10 [6%])、高血压 (八 [4%]）、铁超载（七 [4%]）和 COVID-19 肺炎（六 [3%]）。两组中最常见的严重治疗相关不良事件是肺炎（9 名 [5%] luspatercept 接受者和 13 名 [7%] epoetin alfa 接受者）和 COVID-19（8 名 [4%] luspatercept 接受者和 10 名 [6%] 接受者阿尔法依泊汀接受者）。中期分析中报告了 1 例死亡（由于急性髓系白血病），被认为与 luspatercept 相关。 Luspatercept 代表了一种新的治疗标准，用于治疗未接受过 ESA 的患有输血依赖性、低风险骨髓增生异常综合征的患者。 与阿法依泊汀相比，使用 luspatercept 的患者有明显更多的红细胞输注独立性和血液学改善，并且在患者亚组中观察到了益处。 Celgene 和 Acceleron Pharma。