Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial

医学 红细胞生成 中期分析 艾博汀阿尔法 骨髓增生异常综合症 贫血 国际预后积分系统 补血的 促红细胞生成素 临床试验 内科学 外科 骨髓
作者
Uwe Platzbecker,Matteo Giovanni Della Porta,Valeria Santini,Amer M. Zeidan,Rami S. Komrokji,Jake Shortt,David Valcárcel,Anna Jonášová,Sophie Dimicoli‐Salazar,Ing Soo Tiong,Chien‐Chin Lin,Jiahui Li,Jennie Zhang,Ana Carolina Giuseppi,Sandra Kreitz,Veronika Pozharskaya,Karen L. Keeperman,Shelonitda Rose,Jeevan K. Shetty,Sheida Hayati,Sadanand Vodala,Thomas Prébet,Andrius Degulys,Stefania Paolini,Thomas Cluzeau,Pierre Fenaux,Guillermo Garcia‐Manero
出处
期刊:The Lancet [Elsevier]
卷期号:402 (10399): 373-385 被引量:68
标识
DOI:10.1016/s0140-6736(23)00874-7
摘要

Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with lower-risk myelodysplastic syndromes. In this study, we report the results of a prespecified interim analysis of luspatercept versus epoetin alfa for the treatment of anaemia due to lower-risk myelodysplastic syndromes in the phase 3 COMMANDS trial.The phase 3, open-label, randomised controlled COMMANDS trial is being conducted at 142 sites in 26 countries. Eligible patients were aged 18 years or older, had a diagnosis of myelodysplastic syndromes of very low risk, low risk, or intermediate risk (per the Revised International Prognostic Scoring System), were ESA-naive, and required red blood cell transfusions (2-6 packed red blood cell units per 8 weeks for ≥8 weeks immediately before randomisation). Integrated response technology was used to randomly assign patients (1:1, block size 4) to luspatercept or epoetin alfa, stratified by baseline red blood cell transfusion burden (<4 units per 8 weeks vs ≥4 units per 8 weeks), endogenous serum erythropoietin concentration (≤200 U/L vs >200 to <500 U/L), and ring sideroblast status (positive vs negative). Luspatercept was administered subcutaneously once every 3 weeks starting at 1·0 mg/kg body weight with possible titration up to 1·75 mg/kg. Epoetin alfa was administered subcutaneously once a week starting at 450 IU/kg body weight with possible titration up to 1050 IU/kg (maximum permitted total dose of 80 000 IU). The primary endpoint was red blood cell transfusion independence for at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), assessed in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. The COMMANDS trial was registered with ClinicalTrials.gov, NCT03682536 (active, not recruiting).Between Jan 2, 2019 and Aug 31, 2022, 356 patients were randomly assigned to receive luspatercept (178 patients) or epoetin alfa (178 patients), comprising 198 (56%) men and 158 (44%) women (median age 74 years [IQR 69-80]). The interim efficacy analysis was done for 301 patients (147 in the luspatercept group and 154 in the epoetin alfa group) who completed 24 weeks of treatment or discontinued earlier. 86 (59%) of 147 patients in the luspatercept group and 48 (31%) of 154 patients in the epoetin alfa group reached the primary endpoint (common risk difference on response rate 26·6; 95% CI 15·8-37·4; p<0·0001). Median treatment exposure was longer for patients receiving luspatercept (42 weeks [IQR 20-73]) versus epoetin alfa (27 weeks [19-55]). The most frequently reported grade 3 or 4 treatment-emergent adverse events with luspatercept (≥3% patients) were hypertension, anaemia, dyspnoea, neutropenia, thrombocytopenia, pneumonia, COVID-19, myelodysplastic syndromes, and syncope; and with epoetin alfa were anaemia, pneumonia, neutropenia, hypertension, iron overload, COVID-19 pneumonia, and myelodysplastic syndromes. The most common suspected treatment-related adverse events in the luspatercept group (≥3% patients, with the most common event occurring in 5% patients) were fatigue, asthenia, nausea, dyspnoea, hypertension, and headache; and none (≥3% patients) in the epoetin alfa group. One death after diagnosis of acute myeloid leukaemia was considered to be related to luspatercept treatment (44 days on treatment).In this interim analysis, luspatercept improved the rate at which red blood cell transfusion independence and increased haemoglobin were achieved compared with epoetin alfa in ESA-naive patients with lower-risk myelodysplastic syndromes. Long-term follow-up and additional data will be needed to confirm these results and further refine findings in other subgroups of patients with lower-risk myelodysplastic syndromes, including non-mutated SF3B1 or ring sideroblast-negative subgroups.Celgene and Acceleron Pharma.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
寻道图强应助踏实的寒烟采纳,获得30
1秒前
2秒前
体贴幼晴发布了新的文献求助10
3秒前
ALDXL完成签到,获得积分10
3秒前
4秒前
海子发布了新的文献求助10
4秒前
5秒前
5秒前
妮妮你完成签到,获得积分10
7秒前
大模型应助Wshtiiiii采纳,获得10
7秒前
8秒前
罗是一发布了新的文献求助10
8秒前
8秒前
8秒前
9秒前
彭于晏应助林夏采纳,获得10
10秒前
沉默水风发布了新的文献求助10
10秒前
11秒前
11秒前
12秒前
薰硝壤应助元谷雪采纳,获得10
12秒前
qkdwwz发布了新的文献求助10
14秒前
14秒前
lishan发布了新的文献求助10
15秒前
15秒前
15秒前
高一完成签到,获得积分10
16秒前
高高涵梅关注了科研通微信公众号
17秒前
18秒前
852应助武坤采纳,获得10
18秒前
19秒前
英俊鼠标发布了新的文献求助10
19秒前
19秒前
20秒前
20秒前
20秒前
21秒前
陈秋发布了新的文献求助10
22秒前
23秒前
luo完成签到,获得积分10
24秒前
高分求助中
Sustainability in Tides Chemistry 2800
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
Rechtsphilosophie 1000
Bayesian Models of Cognition:Reverse Engineering the Mind 888
Le dégorgement réflexe des Acridiens 800
Defense against predation 800
Very-high-order BVD Schemes Using β-variable THINC Method 568
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3136013
求助须知:如何正确求助?哪些是违规求助? 2786835
关于积分的说明 7779716
捐赠科研通 2443045
什么是DOI,文献DOI怎么找? 1298822
科研通“疑难数据库(出版商)”最低求助积分说明 625232
版权声明 600870