Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial.

The aim of this study is to report overall survivalfrom the second interim analysis, with extended follow-up.

本研究旨在报告第二次中期分析的总生存期数据，随访时间延长。

Methods

In the ongoing global, open-label, randomised, phase 3 DREAMM-7 trial done at 142 study centres (research facilities, hospitals, and institutions) in 20 countries across North America, South America, Europe, and the Asia-Pacific region, eligible patients were aged at least 18 years and had confirmed multiple myeloma (according to International Myeloma Working Group criteria), an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and progression on or after at least one previous line of therapy.

在一项正在进行的全球性、开放标签、随机、第三阶段DREAMM-7试验中，该试验在北美、南美、欧洲和亚太地区的20个国家的142个研究中心（研究设施、医院和机构）进行，符合条件的患者年龄至少为18岁，且根据国际骨髓瘤工作组的标准，确诊为多发性骨髓瘤，东部肿瘤协作组（ECOG）表现状态为0-2，且在至少一种先前治疗线后疾病进展。

Patients were randomly assigned (1:1) by use of a central interactive response technology system to receive BVd, which comprised belantamab mafodotin 2·5 mg/kg intravenously every 3 weeks plus bortezomib 1·3 mg/m2 subcutaneously (twice weekly in 21-day cycles, for up to eight cycles) plus dexamethasone 20 mg orally or intravenously (on the day of, and after, bortezomib; for up to eight cycles), or DVd, which comprised daratumumab 16 mg/kg intravenously (21-day cycles; once weekly in cycles 1-3, every 3 weeks in cycles 4-8, and every 4 weeks in cycle 9 and beyond) plus bortezomib and dexamethasone; bortezomib and dexamethasone doses and schedules were the same as those in the BVd group.

患者通过使用中央交互式响应技术系统以1:1的比例随机分配接受BVd治疗，该治疗包括每3周静脉注射2.5 mg/kg的belantamab mafodotin，皮下注射1.3 mg/m2的bortezomib（21天为一个周期，每周两次，最多八个周期）以及口服或静脉注射20 mg的地塞米松（在bortezomib当天及之后，最多八个周期），或者接受DVd治疗，该治疗包括每21天一个周期静脉注射16 mg/kg的daratumumab（第1-3周期每周一次，第4-8周期每3周一次，第9周期及以后每4周一次）以及与BVd组相同的bortezomib和地塞米松剂量和方案；bortezomib和地塞米松剂量和方案与BVd组相同。

Randomisation was stratified by number of previous lines of therapy, previous bortezomib, and Revised International Staging System stage.

随机化根据先前治疗线数、之前是否使用过硼替佐米以及修订版国际分期系统（R-ISS）阶段进行分层。

Treatment assignments were unmasked for study personnel and patients; however, they were masked to the independent review committee.

治疗分配对研究人员和患者是未设盲的；然而，他们对独立评审委员会是设盲的。

Patients received treatment until progressive disease, death, unacceptable toxicity, withdrawal of consent, or loss to follow-up, whichever occurred first.

患者接受治疗直至疾病进展、死亡、出现不可接受的毒性、撤回同意或失访，以先发生者为准。

The primary endpoint was progression-free survival; key secondary endpoints were overall survival, minimal residual disease negativity in patients with a complete response or better, duration of response to treatment, and safety.

主要终点是无进展生存期；关键次要终点包括总生存期、完全缓解或更好患者的微小残留病灶阴性、治疗反应持续时间以及安全性。

Analysis of efficacy endpoints was based on assessments in all patients who were randomly assigned (ie, the intention-to-treatpopulation).

疗效终点的分析基于所有被随机分配的患者（即意向治疗人群）的评估。

The safety population included all randomly assigned patients who received one or more doses of study treatment.

安全性人群包括所有接受了一次或多次研究治疗的随机分配患者。

This trial is registered with ClinicalTrials.gov, NCT04246047, and is ongoing.

该试验已在ClinicalTrials.gov上注册，编号为NCT04246047，并正在进行中。

Results

From May 7, 2020, to June 28, 2021, of 623 patients assessed for eligibility, 494 were randomly assigned to receive BVd (n=243) or DVd (n=251); 272 (55%) were male, and 409 (83%) were White.

从2020年5月7日至2021年6月28日，共有623名患者进行了资格评估，其中494名被随机分配接受BVd（n=243）或DVd（n=251）治疗；272名（55%）为男性，409名（83%）为白人。

The median age of the patients was 64·5 years (IQR 57·0-71·0).

患者的中位年龄为64.5岁（四分位数间距57.0-71.0）。

At the updated data cutoff (Oct 7, 2024) and median follow-up (39·4 months [IQR 14·6-42·9]), early, sustained, and significant overall survivalbenefit was observed with BVd versus DVd.

在最近的数据截止日期（2024年10月7日）和中位随访时间（39.4个月，四分位数间距14.6-42.9）时，与DVd相比，BVd显示出早期、持续且显著的总生存获益。

Median overall survivalwas not reached (NR; 95% CI NR-NR) with BVd and NR (41·0 months-NR) with DVd (hazard ratio[HR] 0·58; 95% CI 0·43-0·79; p=0·0002).

中位总生存期未达到（NR; 95% 置信区间 NR-NR）使用BVd治疗，以及NR（41.0个月-NR）使用DVd治疗（风险比[HR] 0.58; 95% 置信区间 0.43-0.79; p=0.0002）。

BVd versus DVd led to greater than double the minimal residual disease-negativity rates in patients with a complete response or better (25% [95% CI 19·8%-31·0%] vs 10% [6·9%-14·8%]) and median duration of response (40·8 months [95% CI 30·5 months-NR] vs 17·8 months [13·8-23·6]).

与DVd相比，使用BVd治疗的患者在完全缓解或更好的情况下，最小残留病灶阴性率超过两倍（25% [95% 置信区间 19.8%-31.0%] 对比 10% [6.9%-14.8%]），以及反应持续时间的中位数（40.8个月 [95% 置信区间 30.5个月-NR] 对比 17.8个月 [13.8-23.6]）。

Analysis of progression-free survival2 showed that the treatment benefit favouring BVd versus DVd was maintained following subsequent antimyeloma therapy; median progression-free survival2 was NR with BVd (95% CI 45·6-NR) versus 33·4 months (95% CI 26·7-44·9) with DVd (HR, 0·59; 95% CI, 0·45-0·77).

无进展生存期2的分析显示，与DVd相比，BVd治疗的益处在随后的抗骨髓瘤治疗后得以维持；BVd组的中位无进展生存期2为未达到（95%置信区间45.6-未达到），而DVd组为33.4个月（95%置信区间26.7-44.9）（风险比，0.59；95%置信区间，0.45-0.77）。

The most common grade 3 or 4 adverse eventwas thrombocytopenia (135 [56%] of 242 with BVd vs 87 [35%] of 246 with DVd).

最常见的3级或4级不良事件是血小板减少症（BVd组242例中有135例[56%]，而DVd组246例中有87例[35%]）。

Serious adverse events occurred in 129 (53%) of 242 patients receiving BVd and 94 (38%) of 246 patients receiving DVd; the most common events were pneumonia (29 [12%] vs 11 [4%]), pyrexia (12 [5%] vs 10 [4%]), and COVID-19 (11 [5%] vs 10 [4%]).

在接受BVd治疗的242名患者中，有129名（53%）和接受DVd治疗的246名患者中有94名（38%）发生了严重不良事件；最常见的事件是肺炎（29名[12%]对比11名[4%]）、发热（12名[5%]对比10名[4%]）和COVID-19（11名[5%]对比10名[4%]）。

Treatment-related serious adverse events that led to death occurred in seven (3%) of 242 patients receiving BVd (pneumonia [n=4], gastrointestinal haemorrhage [n=1], subdural haemorrhage [n=1], or mesenteric vessel thrombosis [n=1]) and two (1%) of 246 receiving DVd (COVID-19 [n=2]).

与治疗相关的导致死亡的严重不良事件发生在接受BVd治疗的242名患者中的七名（3%）（肺炎[n=4]，胃肠道出血[n=1]，硬膜下出血[n=1]，或肠系膜血管血栓形成[n=1]）和接受DVd治疗的246名患者中的两名（1%）（COVID-19 [n=2]）。

interpretation

DREAMM-7 showed significant and clinically meaningful overall survival, progression-free survival, minimal residual disease negativity, and duration of response benefits with BVd versus DVd.

DREAMM-7 研究显示，与 DVd 相比，BVd 在总生存、无进展生存、微小残留病灶阴性以及反应持续时间方面具有显著且具有临床意义的改善。

BVd could be a new standard of care for RRMM.

BVd 可能成为复发/难治性多发性骨髓瘤（RRMM）的新标准治疗方案。

funding

GSK.

葛兰素史克。