Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial.

We report here patient-reported outcomes.

我们在这里报告了患者报告的结果。

Methods

In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 106 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone).

在正在进行的、第3阶段、开放标签的CARTITUDE-4研究中，患者从美国、欧洲、亚洲和澳大利亚的81个地点招募，并按1:1的比例随机分配至cilta-cel组（目标剂量为0·75 × 10^6 CAR-T细胞/kg）或标准治疗组（达雷妥尤单抗、泊马度米、地塞米松；泊马度米、硼替佐米和地塞米松）。

Eligible patients had relapsed, lenalidomide-refractory multiple myeloma, received one to three previous treatment lines including a proteasome inhibitor and an immunomodulatory drug, and had an ECOG performance status of 0 or 1.

符合条件的患者有复发性、来那度胺耐药的多发性骨髓瘤，接受了一至三线治疗，包括一种蛋白酶体抑制剂和一种免疫调节药物，并且ECOG表现状态为0或1。

Secondary endpoints reported here include time to sustained worsening of symptoms (Multiple Myeloma Symptom and Impact Questionnaire [MySIm-Q]; a key secondary endpoint) and change in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core C30 (intention-to-treatpopulation) and EuroQol 5-Dimension 5-Level (EQ-5D-5L; intention-to-treatpopulation).

这里报告的次要终点包括症状持续恶化的时间（多重骨髓瘤症状和影响问卷[MySIm-Q]；一个关键的次要终点）以及欧洲癌症研究与治疗组织（EORTC）生活质量（QoL）问卷核心C30（意向治疗人群）和欧洲五维五级健康量表（EQ-5D-5L；意向治疗人群）的变化。

This study is registered with ClinicalTrials.gov number NCT04181827 and is ongoing.

这项研究已在ClinicalTrials.gov上注册，编号为NCT04181827，并正在进行中。

Results

Patients were enrolled from July 10, 2020, to Nov 17, 2021, and 419 of 516 screened patients were randomly assigned (cilta-cel, n=208; standard of care, n=211; median follow-up, 15·9 months [IQR 12·4 to 17·8]); median age was 61 years. 191 (92%) of 208 patients in the cilta-cel group and 190 (91%) of 209 evaluable patients in the standard- of-care group completed baseline assessments.

患者从2020年7月10日至2021年11月17日被纳入研究，516名筛查患者中有419名被随机分配（cilta-cel组，n=208；标准治疗组，n=211；中位随访时间为15.9个月[四分位数间距12.4至17.8]）；中位年龄为61岁。在cilta-cel组的208名患者中，有191名（92%）和在标准治疗组的209名可评估患者中，有190名（91%）完成了基线评估。

MySIm-Q compliance post-baseline was 70 to 81% (cilta-cel) and 79 to 89% (standard of care).

基线后MySIm-Q的依从性为70%至81%（cilta-cel组）和79%至89%（标准治疗组）。

MySIm-Q median time to sustained symptom worsening with cilta-cel versus standard of care was 23·7 versus 18·9 months (HR 0·42; 95% CI 0·26 to 0·68). 12-month mean changes for EORTC global health status (GHS) were +10·1 (95% CI 7·0 to 13·1) and -1·5 (95% CI -5·3 to 2·3) points and were +8·0 (95% CI 5·2 to 10·7) and +1·4 (95% CI -1·9 to 4·7) points for EQ-5D-5L visual analogue scale (VAS).

MySIm-Q 中位时间至持续症状恶化在使用 cilta-cel 与标准治疗组分别为 23.7 个月与 18.9 个月（HR 0.42; 95% 置信区间 0.26 至 0.68）。12个月时，EORTC 全球健康状况（GHS）的平均变化为 +10.1（95% 置信区间 7.0 至 13.1）和 -1.5（95% 置信区间 -5.3 至 2.3）点，而 EQ-5D-5L 视觉模拟量表（VAS）的平均变化为 +8.0（95% 置信区间 5.2 至 10.7）和 +1.4（95% 置信区间 -1.9 至 4.7）点。

Rates of clinically meaningful improvements in GHS and VAS were higher with cilta-cel than with standard of care.

与标准治疗相比，使用 cilta-cel 的患者在 GHS 和 VAS 上达到临床意义改善的比例更高。

interpretation

Health-related QoL improvements and delayed symptom worsening support cilta-cel's clinical efficacy in lenalidomide-refractory disease.

健康相关的生活质量改善和症状恶化延迟支持了cilta-cel在雷利度胺耐药疾病中的临床疗效。

funding

Janssen Research & Development, Legend Biotech USA.

杨森研发，传奇生物美国公司。