Long-term efficacy and safety of luspatercept for the treatment of anaemia in patients with transfusion-dependent β-thalassaemia (BELIEVE): final results from a phase 3 randomised trial.

Here, we report long-term follow-up data from the phase 3 BELIEVE trial of luspatercept for transfusion-dependent β-thalassaemia.

在这里，我们报告了针对输血依赖性β-地中海贫血的luspatercept的3期BELIEVE试验的长期随访数据。

Methods

BELIEVE was a phase 3, randomised, double-blind, placebo-controlledstudy performed at 65 sites in 15 countries.

BELIEVE 是一项在15个国家的65个地点进行的3期、随机、双盲、安慰剂对照研究。

The trial included adults with transfusion-dependent β-thalassaemia or haemoglobin E/β-thalassaemia and Eastern Cooperative Oncology Group score of 0-1.

该试验包括了需要输血的成人β-地中海贫血或血红蛋白E/β-地中海贫血患者，以及东部肿瘤协作组评分为0-1分的患者。

Patients were randomly assigned (2:1) using integrated response technology stratified by region to luspatercept (1·0-1·25 mg/kg) or placebo administered subcutaneously once every 21 days.

患者通过集成响应技术按2:1的比例随机分配，按地区分层，接受每21天皮下注射一次的luspatercept（1·0-1·25 mg/kg）或安慰剂治疗。

After study unblinding, patients could receive luspatercept in the open-label extension phase (crossover allowed).

研究揭盲后，患者可以在开放标签扩展阶段接受luspatercept治疗（允许交叉）。

The primary endpoint results (proportion of patients with reduction in transfusion burden of ≥33% and ≥2 RBC units during weeks 13-24) are described elsewhere; herein we present an update to the primary endpoint analysis consequent to late-reported transfusion events.

主要终点结果（在第13至24周期间，减少输血负担≥33%且减少≥2单位红细胞的患者比例）已在其他地方描述；在这里，我们提供了主要终点分析的更新，这是由于晚期报告的输血事件所致。

We also report long-term efficacy (intention-to-treatpopulation) and safety data (safety population) for patients followed up for approximately 3 years.

我们还报告了长期疗效（意向治疗人群）和安全性数据（安全性人群），这些数据来自于大约3年随访的患者。

This trial is registered on ClinicalTrials.gov (NCT02604433) and is completed.

该试验已在ClinicalTrials.gov上注册（NCT02604433），并已完成。

Results

Between May 2, 2016, and May 16, 2017, 336 patients were randomly assigned to luspatercept (n=224) or placebo (n=112).

在2016年5月2日至2017年5月16日期间，336名患者被随机分配接受luspatercept治疗（n=224）或安慰剂（n=112）。

The median age of patients was 30 years (IQR 23-40); 195 (58%) were female and 141 (42%) male.

患者的中位年龄为30岁（四分位数间距23-40岁）；其中195名（58%）为女性，141名（42%）为男性。

As of Jan 5, 2021, the median duration of treatment in the luspatercept group was 153·6 weeks (IQR 81·0-171·0) and median study follow-up was 163·1 weeks (140·5-176·2).

截至2021年1月5日，luspatercept组的中位治疗持续时间为153.6周（四分位数间距81.0-171.0周），中位研究随访时间为163.1周（140.5-176.2周）。

Due to the difference in treatment duration between the luspatercept and placebo groups, no comparative analyses between the two groups were performed after week 96.

由于卢斯帕特塞普组和安慰剂组治疗持续时间的差异，96周后两组之间未进行比较分析。

Patients in the luspatercept group showed a sustained reduction in RBC transfusion burden from baseline through week 192, with mean decreases of 6·2 RBC units (SD 5·7) during weeks 97-144 and 6·4 RBC units (4·3) during weeks 145-192.

卢斯帕特塞普组的患者从基线到第192周显示出红细胞输注负担的持续减轻，第97-144周平均减少6.2个红细胞单位（标准差5.7），第145-192周平均减少6.4个红细胞单位（标准差4.3）。

In the luspatercept group, a 33% or greater reduction in transfusion burden from baseline was observed in 173 (77%) patients over any 12-week interval and in 116 (52%) patients over any 24-week interval. The median total duration of 33% or greater transfusion burden reduction response during any period of at least 12 weeks was 586·0 days (IQR 264·0-1010·0).

在使用luspatercept的组别中，有173名（77%）患者在任何12周间隔期间观察到从基线起输血负担减少33%或更多，而在任何24周间隔期间有116名（52%）患者观察到输血负担减少33%或更多。在任何至少持续12周的期间内，33%或更多输血负担减少反应的总持续时间的中位数为586.0天（四分位数间距264.0-1010.0）。

The most common grade 3 or worse treatment-emergent adverse events (TEAEs) among all patients who received luspatercept (n=315, including 92 patients who crossed over after study unblinding) were anaemia (nine [3%]), increased liver iron concentration (seven [2%]), and bone pain (seven [2%]); serious TEAEs occurred in 71 (23%) patients.

所有接受luspatercept治疗的患者（n=315，包括92名在研究解盲后交叉治疗的患者）中最常见的3级或更严重的治疗后不良事件（TEAEs）是贫血（九例[3%]）、肝铁浓度增加（七例[2%]）和骨痛（七例[2%]）；有71名（23%）患者发生了严重的TEAEs。

No treatment-related deaths occurred in any group during the study.

在研究期间，任何组别中均未发生与治疗相关的死亡事件。

interpretation

These long-term results affirm luspatercept's efficacy in addressing key unmet needs of patients with transfusion-dependent β-thalassaemia with a manageable safety profile.

这些长期结果证实了luspatercept在解决输血依赖性β-地中海贫血患者的关键未满足需求方面的有效性，并具有可管理的安全性特征。

funding

Celgene and Acceleron Pharma.

赛尔基因和加速制药公司。