BACKGROUND Elotuzumab plus lenalidomide and dexamethasone has shown improved progression-free and overall survival versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. We aimed to assess these regimens in patients with newly diagnosed multiple myeloma who are ineligible for haematopoietic stem-cell transplantation (HSCT). METHODS ELOQUENT-1 is an open-label, multicentre, randomised, phase 3 trial conducted at 185 hospitals, oncology practices, and research centres in 19 countries. Eligible patients were aged 18 years or older with newly diagnosed, untreated, symptomatic myeloma and not candidates for high-dose therapy plus HSCT, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower. Patients were randomly assigned (1:1) to receive elotuzumab plus lenalidomide and dexamethasone or lenalidomide and dexamethasone using an interactive voice response system, stratified by the International Staging System (ISS; stage I-II vs III), age (<75 years vs ≥75 years), and ECOG performance status (0 vs 1-2). Patients in the elotuzumab plus lenalidomide and dexamethasone group received elotuzumab administered intravenously at 10 mg/kg on days 1, 8, 15, and 22 during cycles 1 and 2, days 1 and 15 during cycles 3-18, and then at 20 mg/kg on day 1 for subsequent cycles. In both treatment groups, patients received 25 mg lenalidomide orally on days 1-21 of each cycle and 40 mg dexamethasone on days 1, 8, 15, and 22 of each cycle. The primary endpoint was progression-free survival, as per the primary definition from European Society for Blood and Marrow Transplantation criteria in all randomly assigned patients (intention-to-treat population). This study is registered with ClinicalTrials.gov, NCT01335399 (completed). FINDINGS Between Aug 4, 2011, and June 19, 2014, 748 patients were randomly assigned (374 in each treatment group) and 742 patients received treatment (333 (90%) of 371 in the elotuzumab plus lenalidomide and dexamethasone group vs 339 (91%) of 371 in the lenalidomide and dexamethasone group discontinued treatment). The median age of patients was 73·0 years (IQR 69·0-78·0), 294 (39%) patients were 75 years or older. Most patients were White (711 [95%]) and male (412 [55%]). At a minimum follow-up of 65·3 months, the median progression-free survival was not significantly different between the groups: 31·4 months (95% CI 26·2-36·8) in the elotuzumab plus lenalidomide and dexamethasone group versus 29·5 months (23·5-34·3) in the lenalidomide and dexamethasone group (HR 0·93, 95·71% CI 0·77-1·12; stratified log-rank p=0·44). The median follow-up was 70·6 months (IQR 35·1-79·2). The most common grade 3-4 treatment-related adverse event was neutropenia (64 [17%] of 371 vs 79 [21%] of 371). Study drug toxicity was the reported cause of death in five (1%) versus four (1%) patients. INTERPRETATION Elotuzumab plus lenalidomide and dexamethasone did not significantly improve progression-free survival versus lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for HSCT. Although these data contribute to the treatment landscape, further research is needed to find ways to improve treatments in the front-line setting. FUNDING Bristol Myers Squibb.

中文翻译：

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将 elotuzumab 添加到来那度胺和地塞米松治疗新诊断的不适合移植的多发性骨髓瘤 (ELOQUENT-1) 患者：一项开放标签、多中心、随机的 3 期试验。

背景 在复发或难治性多发性骨髓瘤患者中，与来那度胺和地塞米松相比，Elotuzumab 加来那度胺和地塞米松已显示出改善的无进展生存期和总生存期。我们的目的是在新诊断的不适合造血干细胞移植 (HSCT) 的多发性骨髓瘤患者中评估这些方案。方法 ELOQUENT-1 是一项开放标签、多中心、随机、3 期试验，在 19 个国家的 185 家医院、肿瘤学实践和研究中心进行。符合条件的患者年龄在 18 岁或以上，新诊断、未治疗、有症状的骨髓瘤，不适合大剂量治疗加 HSCT，东部肿瘤协作组 (ECOG) 体能状态为 2 或更低。患者被随机分配（1：1) 使用交互式语音应答系统接受 elotuzumab 加来那度胺和地塞米松或来那度胺和地塞米松，按国际分期系统（ISS；I-II 期 vs III 期）、年龄（<75 岁 vs ≥75 岁）和 ECOG 分层表现状态（0 vs 1-2）。elotuzumab 加来那度胺和地塞米松组的患者在第 1 和第 2 周期的第 1、8、15 和 22 天，在第 3-18 周期的第 1 天和第 15 天，以 10 mg/kg 静脉内给药 elotuzumab，然后以 20 mg/kg 的剂量静脉给药。在第 1 天为后续周期的 kg。在两个治疗组中，患者在每个周期的第 1-21 天口服 25 mg 来那度胺，在每个周期的第 1、8、15 和 22 天口服 40 mg 地塞米松。主要终点是无进展生存期，根据欧洲血液和骨髓移植学会标准的主要定义，所有随机分配的患者（意向治疗人群）。该研究已在 ClinicalTrials.gov 注册，NCT01335399（已完成）。结果 2011 年 8 月 4 日至 2014 年 6 月 19 日期间，748 名患者被随机分配（每个治疗组 374 名），742 名患者接受了治疗（埃罗妥珠单抗加来那度胺和地塞米松组 371 名患者中的 333 名（90%）与 339 名（91 %）来那度胺和地塞米松组 371 人停止治疗）。患者的中位年龄为 73·0 岁（IQR 69·0-78·0），294 名（39%）患者年龄在 75 岁或以上。大多数患者是白人 (711 [95%]) 和男性 (412 [55%])。在至少 65·3 个月的随访中，各组之间的中位无进展生存期没有显着差异：elotuzumab 加来那度胺和地塞米松组为 31·4 个月 (95% CI 26·2-36·8)，而来那度胺和地塞米松组为 29·5 个月 (23·5-34·3) (HR 0·93, 95·71% CI 0·77-1·12；分层对数秩 p=0·44)。中位随访时间为 70·6 个月（IQR 35·1-79·2）。最常见的 3-4 级治疗相关不良事件是中性粒细胞减少症（371 例中的 64 例 [17%] 对 371 例中的 79 例 [21%]）。据报道，研究药物毒性是五名（1%）和四名（1%）患者的死亡原因。解释 与来那度胺和地塞米松相比，在不适合 HSCT 的新诊断多发性骨髓瘤患者中，Elotuzumab 加来那度胺和地塞米松未显着改善无进展生存期。尽管这些数据有助于治疗前景，需要进一步研究以找到改善一线治疗的方法。资助百时美施贵宝。