Venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed or refractory multiple myeloma (BELLINI): final overall survival results from a randomised, phase 3 study.

However, venetoclax showed increased early mortality.

然而，venetoclax显示出早期死亡率增加。

Here, we report the final overall survivalanalysis.

在这里，我们报告了最终的总生存分析。

Methods

The randomised, double-blind, multicentre, phase 3 BELLINI study enrolled patients aged 18 years or older with relapsed or refractory multiple myeloma, Eastern Cooperative Oncology Group performance status of 2 or less, and one to three previous therapies, across 90 hospitals in 16 countries.

随机、双盲、多中心的第三阶段BELLINI研究招募了18岁或以上的患者，这些患者患有复发或难治性多发性骨髓瘤，Eastern Cooperative Oncology Group表现状态为2或更差，并且接受过一到三次的先前治疗，研究在16个国家的90家医院进行。

Eligible patients were centrally randomly assigned (2:1, stratified by previous proteasome inhibitor exposure and number of previous lines of therapies) via interactive response technology system (block size 3) to once-daily venetoclax (800 mg orally) or placebo with bortezomib (1·3 mg/m2 subcutaneously or intravenously) and dexamethasone (20 mg orally), administered in 21-day cycles for initial eight cycles, followed by 35-day cycles until discontinuation.

符合条件的患者通过交互式响应技术系统（阻塞大小为3）进行中央随机分配（2:1，按先前蛋白酶体抑制剂暴露和先前治疗线数分层），每天一次口服800毫克的维奈克拉或与硼替佐米（皮下或静脉注射1.3 mg/m2）和地塞米松（口服20 mg）联合使用安慰剂，初始八个周期为21天，随后直到停药为35天周期。

The primary endpoint was progression-free survivalas assessed by an independent review committee in the intention-to-treatpopulation; this analysis reports overall survivaland investigator-assessed progression-free survivalin the intention-to-treatpopulation.

主要终点是独立评审委员会评估的无进展生存期，在意向治疗人群中；本分析报告了意向治疗人群中的总生存期和研究者评估的无进展生存期。

Safety analyses were done in patients who received at least one dose of the study drug.

在至少接受过一次研究药物治疗的患者中进行了安全性分析。

This study is registered with ClinicalTrials.gov (NCT02755597) and is completed.

该研究已在ClinicalTrials.gov注册（注册号NCT02755597），研究已完成。

Results

From July 19, 2016, to Oct 31, 2017, 291 patients were assigned to venetoclax (n=194) or placebo (n=97); 33 patients (28 in the venetoclax group and five in the placebo group) remained on treatment at the time of this analysis.

从2016年7月19日至2017年10月31日，共有291名患者被分配到维奈克拉组（n=194）或安慰剂组（n=97）；在本分析时点，有33名患者（维奈克拉组28人，安慰剂组5人）仍在接受治疗。

Of the 291 patients, 152 (52%) were men and 139 (48%) were women. 87 (30%) of 291 patients were Asian, 12 (4%) were Black or African American, 190 (65%) were White, and 32 (11%) were Hispanic or Latino.

在291名患者中，152名（52%）为男性，139名（48%）为女性。291名患者中有87名（30%）为亚洲人，12名（4%）为黑人或非裔美国人，190名（65%）为白人，32名（11%）为西班牙裔或拉丁裔。

At 45·6 months (IQR 43·6-48·3) median follow-up, median overall survivalwas not reached in the venetoclax group (not reached [NR] [95% CI 44·4-not estimable]) or in the placebo group (NR [95% CI 44·0-not estimable]; HR 1·19 [95% CI 0·80-1·77]); p=0·39).

在中位随访时间为45.6个月（四分位数间距43.6-48.3）时，维奈克拉组和安慰剂组的中位总生存期均未达到（维奈克拉组未达到[95%置信区间44.4-无法估计]，安慰剂组未达到[95%置信区间44.0-无法估计]；风险比1.19[95%置信区间0.80-1.77]；p=0.39）。

Median progression-free survivalwas 23·4 months (95% CI 16·2-26·4) with venetoclax versus 11·4 months (95% CI 9·5-14·6) with placebo (HR 0·58 [95% CI 0·43-0·78]; p=0·00026).

维奈克拉组的中位无进展生存期为23.4个月（95%置信区间16.2-26.4），而安慰剂组为11.4个月（95%置信区间9.5-14.6）（风险比0.58[95%置信区间0.43-0.78]；p=0.00026）。

The most common grade 3 or 4 adverse events were thrombocytopenia (51 [26%] of 193 in the venetoclax group vs 38 [40%] of 96 in the placebo group]) and neutropenia (58 [30%] of 193 vs eight [8%] of 96 patients).

最常见的3级或4级不良事件是血小板减少症（193名接受维奈克拉组患者中有51名[26%]，而96名接受安慰剂组患者中有38名[40%]）和中性粒细胞减少症（193名中有58名[30%]，而96名中有8名[8%]患者）。

Treatment-related adverse events led to death in four (2%) of 193 patients in the venetoclax group (two patients with pneumonia, one with death, and one with both multiple organ dysfunction syndrome and septic shock) and none in the placebo group.

与治疗相关的不良事件导致维奈克拉组193名患者中有4名（2%）死亡（2名患者死于肺炎，1名死于死亡，1名同时死于多器官功能衰竭和败血性休克），而安慰剂组无患者死亡。

interpretation

Final overall survivalanalysis in the BELLINI study showed overall survivalfavouring placebo over venetoclax and progression-free survivalfavouring venetoclax over placebo, indicating venetoclax usage should be avoided in the general relapsed or refractory multiple myeloma population.

BELLINI研究的最终总生存分析显示，与维奈克拉相比，安慰剂组的总生存期更长，而与安慰剂相比，维奈克拉组的无进展生存期更长，这表明在一般复发或难治性多发性骨髓瘤患者中应避免使用维奈克拉。

funding

AbbVie and Genentech.

AbbVie和Genentech。