Patient-reported outcomes with belantamab mafodotin, bortezomib, and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): results from a phase 3, open-label, randomised controlled trial.

We aimed to evaluate the effect of belantamab mafodotin, bortezomib, and dexamethasone compared with daratumumab, bortezomib, and dexamethasone on health-related quality of life (HRQOL) using various patient-reported outcomes in patients who participated in DREAMM-7.

我们的目标是使用各种患者报告的结果，评估在DREAMM-7研究中参与的患者中，Belantamab mafodotin、硼替佐米和地塞米松与达雷妥尤单抗、硼替佐米和地塞米松相比对健康相关生活质量（HRQOL）的影响。

Methods

This phase 3, open-label, randomised controlled trial, done at 142 hospitals in 20 countries included adult patients aged 18 years or older with relapsed or refractory multiple myeloma who received at least one previous line of therapy and progressed during or after their most recent treatment and had an Eastern Cooperative Oncology Group performance status of 0 to 2.

这项第三阶段、开放标签、随机对照试验在20个国家的142家医院进行，纳入了18岁或以上的成年复发或难治性多发性骨髓瘤患者，这些患者至少接受过一种之前的治疗方案，并在最近一次治疗期间或之后进展，且东部肿瘤协作组（Eastern Cooperative Oncology Group，ECOG）表现状态评分为0至2。

Eligible patients were randomly assigned (1:1) by a central interactive response technology system to receive intravenous belantamab mafodotin (2·5 mg/kg once on day 1 of each 21-day cycle) or intravenous daratumumab (16 mg/kg once a week in cycles 1-3, every 3 weeks in cycles 4-8, and every 4 weeks in cycle 9 and beyond).

符合条件的患者通过中央互动响应技术系统以1:1的比例随机分配，接受静脉注射Belantamab mafodotin（每个21天周期的第1天给予2.5 mg/kg）或静脉注射Daratumumab（第1-3个周期每周一次，第4-8个周期每3周一次，第9个周期及以后每4周一次）。

Patients in both treatment groups also received subcutaneous bortezomib (1·3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles) and oral or intravenous dexamethasone (20 mg on the day of and day after bortezomib administration) for the first 8 cycles.

两组治疗的患者还接受了皮下注射硼替佐米（每21天周期的第1、4、8和11天，剂量为1·3 mg/m2）和口服或静脉注射地塞米松（在硼替佐米给药当天及其后一天，剂量为20 mg），持续8个周期。

Treatment continued until progressive disease, unacceptable toxic effects, withdrawal of consent, or death (whichever occurred first).

治疗将持续进行，直到疾病进展、出现不可接受的毒性反应、撤回同意或死亡（以先发生者为准）。

Patient-reported outcomes were secondary and exploratory objectives.

患者报告的结果是次要和探索性目标。

Secondary patient-reported outcome endpoints were change from baseline in HRQOL, as measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-MY20, and maximum postbaseline score for each item attribute on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

次要患者报告的结果终点是从基线开始的健康相关生活质量的变化，通过欧洲癌症研究与治疗组织（EORTC）QLQ-C30和EORTC QLQ-MY20来测量，以及患者报告的结果版本的不良事件通用术语标准（PRO-CTCAE）中每个项目属性的基线后最大得分。

Exploratory patient-reported outcome endpoints included changes from baseline in symptoms and related effects as measured by Ocular Surface Disease Index (OSDI), change from baseline in FACT-GP5 score, and change from baseline in the EQ-5D VAS.

探索性患者报告的结果终点包括基线时的Ocular Surface Disease Index (OSDI)测量的症状和相关效应的变化、FACT-GP5评分的基线变化，以及EQ-5D VAS的基线变化。

EORTC QLQ-C30, EORTC QLQ-MY20, and FACT-GP5 scores were analysed in the intention-to-treatpopulation, and PRO-CTCAE and OSDI vision-related functioning scores were analysed in the safety population (patients who received at least one dose of treatment).

在意向治疗人群中分析了EORTC QLQ-C30、EORTC QLQ-MY20和FACT-GP5评分，在安全性人群中分析了PRO-CTCAE和OSDI视力相关功能评分（接受至少一次治疗的患者）。

Results were summarised using descriptive statistics.

结果使用描述性统计学进行了总结。

Least-squares mean changes from baseline were estimated using a restricted maximum likelihood-based mixed model.

使用基于限制性极大似然法的混合模型估计了从基线开始的最小二乘均值变化。

This study was registered with ClinicalTrials.gov, NCT04246047, and is ongoing.

该研究已在ClinicalTrials.gov上注册，编号为NCT04246047，并正在进行中。

Results

Between May 7, 2020, and June 28, 2021, 494 patients were included in the intention-to-treatpopulation of the DREAMM-7 study (median follow-up 28·2 months, IQR 14·6-31·4) and were randomly assigned to either belantamab mafodotin, bortezomib, and dexamethasone (n=243) or daratumumab, bortezomib, and dexamethasone (n=251). 222 (45%) of 494 patients were female and 272 (55%) were male.

在2020年5月7日至2021年6月28日期间，共有494名患者被纳入DREAMM-7研究的意向治疗人群（中位随访时间为28.2个月，四分位数间距为14.6-31.4个月），并随机分配到belantamab mafodotin、bortezomib和地塞米松组（n=243）或daratumumab、bortezomib和地塞米松组（n=251）。在494名患者中，222名（45%）为女性，272名（55%）为男性。

The mean age in the total study population was 64·0 years (SD 9·80).

研究总体的平均年龄为64.0岁（标准差9.80）。

Most patients were White (409 [83%] of 494), Asian (61 [12%]), or Black or African American (20 [4%]).

大多数患者为白人（494名中的409名，占83%），亚洲人（61名，占12%），或黑人或非裔美国人（20名，占4%）。

Patients in both groups had stable mean EORTC QLQ-C30 and QLQ-MY20 scores over time.

两组患者的EORTC QLQ-C30和QLQ-MY20平均得分随时间保持稳定。

At each timepoint, most patients reported stable or improved scores in the global health status/quality of life (64 [56%] of 115 patients to 85 [75%] of 114 patients in the belantamab mafodotin group and 105 [51%] of 207 patients to 156 [65%] of 240 patients in the daratumumab group), role functioning (103 [53%] of 196 patients to 77 [68%] of 114 patients in the belantamab mafodotin group and 99 [50%] of 197 patients to 92 [69%] of 134 patients in the daratumumab group), and physical functioning domains (132 [66%] of 201 patients to 101 [77%] of 131 patients in the belantamab mafodotin group and 115 [58%] of 197 patients to 102 [76%] of 134 patients in the daratumumab group) of the EORTC QLQ-C30 and of the disease symptom domain scores of the EORTC QLQ-MY20 (79 [72%] of 109 patients to 95 [83%] of 115 patients in the belantamab mafodotin group and 126 [66%] of 190 patients to 164 [74%] of 221 patients in the daratumumab group).

在每个时间点，大多数患者报告全球健康状况/生活质量（belantamab mafodotin组从115名患者中的64名[56%]到114名患者中的85名[75%]，daratumumab组从207名患者中的105名[51%]到240名患者中的156名[65%]）、角色功能（belantamab mafodotin组从196名患者中的103名[53%]到114名患者中的77名[68%]，daratumumab组从197名患者中的99名[50%]到134名患者中的92名[69%]）和身体功能领域（belantamab mafodotin组从201名患者中的132名[66%]到131名患者中的101名[77%]，daratumumab组从197名患者中的115名[58%]到134名患者中的102名[76%]）的EORTC QLQ-C30以及疾病症状领域得分的EORTC QLQ-MY20（belantamab mafodotin组从109名患者中的79名[72%]到115名患者中的95名[83%]，daratumumab组从190名患者中的126名[66%]到221名患者中的164名[74%]）稳定或有所改善。

Most patients in the belantamab mafodotin group (155 [77%] of 202 to 79 [96%] of 82) and the daratumumab group (155 [86%] of 181 to 60 [100%] of 60) reported being "not at all," "a little," or "somewhat" bothered by treatment side-effects at each visit, as determined by the FACT-GP5.

在belantamab mafodotin组中，202名患者中有155名（77%），在daratumumab组中，181名患者中有155名（86%），在每次随访时，大多数患者报告称治疗副作用“一点也不”、“有一点”或“有些”困扰，这是通过FACT-GP5确定的。

interpretation

HRQOL was generally maintained or improved over time with belantamab mafodotin, bortezomib, and dexamethasone treatment.

随着时间的推移，belantamab mafodotin、硼替佐米和地塞米松治疗通常维持或改善了健康相关生活质量（HRQOL）。

Our findings, in conjunction with previously reported clinical benefits, support the use of belantamab mafodotin as a potential new standard of care in relapsed or refractory multiple myeloma.

我们的发现，结合先前报告的临床益处，支持将belantamab mafodotin作为复发或难治性多发性骨髓瘤的潜在新治疗标准。

funding

GSK.

GSK公司。

translations

For the Polish and Spanish translations of the abstract see Supplementary Materials section.

摘要的波兰语和西班牙语翻译请参见补充材料部分。