Felzartamab plus lenalidomide-dexamethasone versus lenalidomide-dexamethasone for relapsed or refractory multiple myeloma: an open-label, parallel-controlled, randomised, phase 3 trial.

We aimed to evaluate felzartamab, a novel anti-CD38 monoclonal antibody that retains potent antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis while exhibiting markedly attenuated CDC activity in Chinese patients with relapsed or refractory multiple myeloma.

我们旨在评估felzartamab，一种新型抗CD38单克隆抗体，它保留了强大的抗体依赖性细胞毒性（ADCC）和抗体依赖性细胞吞噬作用（ADCP），同时在对中国复发或难治性多发性骨髓瘤患者的研究中表现出显著减弱的CDC活性。

Methods

In this open-label, parallel-controlled, randomised, phase 3 trial conducted at 41 hospitals in China, adults aged 18 years or older with relapsed or refractory multiple myeloma who had received at least one previous line of systemic therapy, and were not refractory to lenalidomide were enrolled.

在这项在中国41家医院进行的开放标签、平行对照、随机、III期试验中，纳入了18岁或以上的成人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系统性治疗，并且对来那度胺没有耐药性。

Patients were randomly assigned (2:1) through a central interactive web response system, stratified by International Staging System stage, number of previous lines of therapy, and previous lenalidomide exposure, to receive intravenous felzartamab (16 mg/kg on days 1 and 4 during week 1, weekly week 2-12, every 2 weeks week 13-24, and every 4 weeks thereafter) plus once daily lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) and once weekly oral dexamethasone (40 mg for patients aged ≤75 years and 20 mg for those >75 years) or lenalidomide and dexamethasone alone.

患者通过中央互动网络响应系统随机分配（2:1），按国际分期系统阶段、既往治疗线数和既往来那度胺暴露情况进行分层，接受静脉注射felzartamab（第1周第1天和第4天各16 mg/kg，第2-12周每周一次，第13-24周每两周一次，之后每四周一次）加上每日一次口服来那度胺（每28天周期的第1-21天25 mg）和每周一次口服地塞米松（≤75岁的患者40 mg，>75岁的患者20 mg）或仅来那度胺和地塞米松。

The primary endpoint was progression-free survival, defined as the time from randomisation to disease progression or death from any cause, whichever occurred first, assessed by an independent review committee in the full analysis set (all randomly assigned patients who received at least one dose of study treatment).

主要终点是无进展生存期，定义为从随机分组到疾病进展或因任何原因死亡的时间，以先发生者为准，由独立审查委员会在全分析集（所有接受至少一次研究治疗的随机分配患者）中评估。

Safety was assessed in all patients who received at least one dose of study treatment.

所有至少接受过一次研究治疗的患者均进行了安全性评估。

This trial is registered with ClinicalTrials.gov (NCT03952091) and is closed to enrolment.

该试验已在ClinicalTrials.gov注册（NCT03952091），目前不再接受患者入组。

Results

Between March 27, 2019, and Oct 20, 2021, 390 patients were assessed for eligibility, 295 of whom were enrolled and randomly assigned to felzartamab plus lenalidomide-dexamethasone (n=195) or lenalidomide-dexamethasone (n=100).

从2019年3月27日至2021年10月20日，共有390名患者被评估是否符合入组资格，其中295名患者被纳入并随机分配到felzartamab加来那度胺-地塞米松组（n=195）或来那度胺-地塞米松组（n=100）。

The full analysis set included 289 patients (191 in the felzartamab plus lenalidomide-dexamethasone group and 98 in the lenalidomide-dexamethasone group). 185 (64%) of 289 patients were male, 104 (36%) were female, and all were of Asian ethnicity.

全分析集包括289名患者（felzartamab联合lenalidomide-dexamethasone组191名和lenalidomide-dexamethasone组98名）。在289名患者中，185名（64%）为男性，104名（36%）为女性，所有患者均为亚洲人种。

At a median follow-up of 34·5 months (IQR 16·8-40·2) in the felzartamab plus lenalidomide-dexamethasone group and 28·7 months (10·8-38·8) in the lenalidomide-dexamethasone group, median progression-free survivalwas 18·9 months (95% CI 13·6-24·0) with felzartamab plus lenalidomide-dexamethasone versus 10·4 months (5·8-13·9) with lenalidomide-dexamethasone (hazard ratio0·62 [95% CI 0·45-0·86]; p=0·0035).

在felzartamab联合lenalidomide-dexamethasone组的中位随访时间为34.5个月（四分位数间距16.8-40.2）和lenalidomide-dexamethasone组的28.7个月（四分位数间距10.8-38.8）时，felzartamab联合lenalidomide-dexamethasone组的中位无进展生存期为18.9个月（95%置信区间13.6-24.0），而lenalidomide-dexamethasone组为10.4个月（5.8-13.9）（风险比0.62 [95%置信区间0.45-0.86]；p=0.0035）。

The most common grade 3-4 adverse events were neutropenia (105 [55%] of 192 vs 22 [23%] of 97), lymphopenia (79 [41%] vs 15 [15%]), leukopenia (74 [39%] vs 11 [11%]), thrombocytopenia (49 [26%] vs 11 [11%]), pneumonia (44 [23%] vs 13 [13%]), anaemia (33 [17%] vs 19 [20%]), hypokalaemia (30 [16%] vs ten [10%]), and upper respiratory tract infection (15 [8%] vs two [2%]).

最常见的3-4级不良事件是中性粒细胞减少症（felzartamab联合lenalidomide-dexamethasone组192名患者中的105名[55%]，lenalidomide-dexamethasone组97名患者中的22名[23%]）、淋巴细胞减少症（79名[41%] vs 15名[15%]）、白细胞减少症（74名[39%] vs 11名[11%]）、血小板减少症（49名[26%] vs 11名[11%]）、肺炎（44名[23%] vs 13名[13%]）、贫血（33名[17%] vs 19名[20%]）、低钾血症（30名[16%] vs 10名[10%]）和上呼吸道感染（15名[8%] vs 2名[2%]）。

The most common serious adverse eventwas pneumonia (42 [22%] vs ten [10%]).

最常见的严重不良事件是肺炎（felzartamab联合lenalidomide-dexamethasone组42名[22%]，lenalidomide-dexamethasone组10名[10%]）。

Treatment-related deaths occurred in 11 (6%) of 192 patients in the felzartamab plus lenalidomide-dexamethasone group (five of unknown cause [possibly related to treatment], two due to pneumonia, one due to febrile infection, one due to cardiac arrest, one due to cerebral infarction, and one due to pneumonitis) and two (2%) of 97 patients in the lenalidomide-dexamethasone group (one due to pneumonia and one due to a fall]).

felzartamab联合lenalidomide-dexamethasone组中有11名（6%）的192名患者发生了与治疗相关的死亡（原因不明[可能与治疗相关]的5名，肺炎2名，发热性感染1名，心脏骤停1名，脑梗死1名，肺炎1名），lenalidomide-dexamethasone组中有2名（2%）的97名患者发生了与治疗相关的死亡（肺炎1名，跌倒1名）。

interpretation

Felzartamab plus lenalidomide-dexamethasone significantly prolonged progression-free survivalcompared with lenalidomide-dexamethasone alone, supporting felzartamab plus lenalidomide-dexamethasone as a potential new treatment option for Chinese patients with relapsed or refractory multiple myeloma.

与单独使用lenalidomide-dexamethasone相比，felzartamab联合lenalidomide-dexamethasone显著延长了无进展生存期，支持felzartamab联合lenalidomide-dexamethasone作为中国复发或难治性多发性骨髓瘤患者的潜在新治疗选择。

funding

TJ Biopharma.

TJ Biopharma。