Safety and efficacy of a dexamethasone-sparing regimen with daratumumab and lenalidomide in patients with frailty and newly diagnosed multiple myeloma (IFM2017-03): a phase 3, open-label, multicentre, randomised, controlled trial.

This study evaluated a dexamethasone-sparing regimen of daratumumab plus lenalidomide versus lenalidomide plus dexamethasone in frail patients with newly diagnosed multiple myeloma.

本研究评估了在体弱且新诊断为多发性骨髓瘤患者中，使用达雷妥尤单抗加雷莫司汀与雷莫司汀加地塞米松的节省地塞米松方案的效果。

Methods

In this prospective, randomised, open-label trial, conducted at 61 active Intergroup Francophone of Myeloma centres, patients aged 65 years or older with newly diagnosed multiple myeloma and an Eastern Cooperative Oncology Group proxy frailty score of 2 or more were randomly assigned 2:1 to receive daratumumab (1800 mg subcutaneously) plus oral lenalidomide (25 mg daily for 21 days of a 28 day cycle) and dexamethasone (20mg weekly) for two cycles (dexamethasone-sparing group) or lenalidomide (25 mg daily) and oral dexamethasone (20 mg weekly; control group), with stratification by International Staging System, age, and centre.

在这项前瞻性、随机、开放标签试验中，61个活跃的法语系骨髓瘤中心参与了研究，年龄在65岁或以上的初诊多发性骨髓瘤患者，且东部肿瘤协作组代理虚弱评分达到2分或以上，被随机分配为2:1接受达雷妥尤单抗（皮下注射1800毫克）加上口服雷那度胺（25毫克，28天周期中的21天）和地塞米松（每周20毫克）治疗两个周期（地塞米松减量组）或仅口服雷那度胺（25毫克）和地塞米松（每周20毫克；对照组），按国际分期系统、年龄和中心进行分层。

The primary endpoint was progression-free survival. Efficacy was assessed in the intention-to-treatpopulation and safety was assessed in all patients exposed to at least one dose of randomised intervention.

主要终点是无进展生存期。疗效在意向治疗人群中评估，安全性在所有至少接受一次随机干预的患者中评估。

This trial is registered with ClinicalTrials.gov, NCT03993912, and is complete.

该试验已在ClinicalTrials.gov注册，注册号为NCT03993912，并已完成。

Results

From Oct 18, 2019 to July 20, 2021, 335 patients were screened, of whom 295 patients were randomly assigned (200 to lenalidomide plus daratumumab, 95 to lenalidomide plus dexamethasone).

从2019年10月18日至2021年7月20日，共对335名患者进行了筛选，其中295名患者被随机分配（200名接受来那度胺联合达雷妥尤单抗治疗，95名接受来那度胺联合地塞米松治疗）。

The median age was 81 years (IQR 77-84), with 180 (61%) aged older than 80 years, and 151 (51%) patients were female and 144 (49%) were male.

中位年龄为81岁（四分位数间距77-84岁），其中180名（61%）患者年龄超过80岁，151名（51%）患者为女性，144名（49%）患者为男性。

Median follow-up was 46·3 months (IQR 46·0-52·7).

中位随访时间为46.3个月（四分位数间距46.0-52.7个月）。

Median progression-free survivalwas 53·4 months (95% CI 35·3-not reached) in the dexamethasone-sparing group versus 22·5 months (16·5-39·0) in the control group (hazard ratio[HR] 0·51, 95% CI 0·37-0·70, p<0·0001).

在去地塞米松组中，中位无进展生存期为53.4个月（95%置信区间35.3-未达到），而在对照组中为22.5个月（16.5-39.0个月）（风险比[HR] 0.51，95%置信区间0.37-0.70，p<0.0001）。

The most common grade 3-5 AEs were neutropenia (110 [55%] of 200 patients in the dexamethasone-sparing group vs 23 [24%] of 95 patients in the control group), and infection (38 [19%] vs 20 [21%]).

最常见的3-5级不良事件是中性粒细胞减少症（去地塞米松组200名患者中有110名[55%]，对照组95名患者中有23名[24%]），以及感染（去地塞米松组38名[19%]，对照组20名[21%]）。

Serious adverse events occurred in 126 patients (63%) in the dexamethasone-sparing group and 66 patients (69%) in the control group.

在减少地塞米松组中有126名患者（63%）发生了严重不良事件，在对照组中有66名患者（69%）发生了严重不良事件。

AEs leading to death occurred in 23 patients (12%) in the dexamethasone-sparing group and 12 patients (13%) in the control group, with 4 (2%) and 2 (2%) grade 5 treatment-emergent adverse events, respectively.

导致死亡的不良事件在减少地塞米松组中有23名患者（12%）发生，在对照组中有12名患者（13%）发生，分别有4名（2%）和2名（2%）为5级治疗相关不良事件。

interpretation

In the IFM2017-03 trial, use of lenalidomide plus daratumumab, with dexamethasone limited to the first 2 treatment cycles, reduced the risk of progression or death compared with lenalidomide plus dexamethasone, with no additional safety concerns.

在IFM2017-03试验中，使用来那度胺加达雷妥尤单抗，仅限于前两个治疗周期使用地塞米松，与仅使用来那度胺加地塞米松相比，降低了疾病进展或死亡的风险，且没有额外的安全问题。

Lenalidomide plus daratumumab could therefore be considered as a treatment option for older patients with frailty and newly diagnosed multiple myeloma.

因此，来那度胺加达雷妥尤单抗可以被视为老年虚弱患者和新诊断的多发性骨髓瘤的治疗选择。

funding

The study was funded by Johnson & Johnson.

该研究由强生公司资助。