Chimeric antigen receptor T-cell therapy idecabtagene vicleucel (ide-cel) showed significantly improved progression-free survival compared with standard regimens in adults with relapsed and refractory multiple myeloma who had received two to four previous regimens in the ongoing phase 3 KarMMa-3 trial (). This study analysed patient-reported outcomes (PROs), a KarMMa-3 secondary endpoint. In the randomised, open-label, phase 3 KarMMa-3 trial, 386 patients in hospitals (≥18 years of age, with measurable disease and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who had received two to four previous regimens—including an immunomodulatory agent, a proteasome inhibitor, and daratumumab—and had documented disease progression after receiving their last dose of the last therapy) were randomly assigned to ide-cel (n=254) or standard regimens (daratumumab, pomalidomide, and dexamethasone; daratumumab, bortezomib, and dexamethasone; ixazomib, lenalidomide, and dexamethasone; carfilzomib and dexamethasone; or elotuzumab, pomalidomide, and dexamethasone; n=132). Patients were expected to complete the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 Questionnaire (QLQ-C30), Multiple Myeloma Module (QLQ-MY20), EQ 5 dimensions (EQ-5D), and EQ-5D visual analogue scale (VAS) at baseline and follow-up timepoints (data cutoff April 18, 2022). PROs included nine prespecified primary domains: EORTC QLQ-C30 GHS–quality of life (QoL), physical functioning, cognitive functioning, fatigue, and pain; QLQ-MY20 disease symptoms and side effects of treatment; and five-level EQ-5D (EQ-5D-5L) index score and EQ-5D visual VAS. Differences in overall least-squares mean changes from baseline to month 20 were analysed using post-hoc constrained longitudinal data analysis. Time to confirmed improvement or deterioration from baseline was analysed using Cox proportional hazard models. Patients were randomly assigned between May 6, 2019, and April 8, 2022. Overall, the median age was 63 years (IQR 55–68); 151 (39%) patients were female; and 250 (65%) patients were White, 36 (9%) Black or African American, 19 (5%) Hispanic or Latino, 12 (3%) Asian, and seven (2%) of other race. The median follow-up was 18·6 months (IQR 14·0–26·4). PRO compliance was higher than 75% throughout. Overall least-squares mean changes from baseline favoured ide-cel with Hedges’ g effect sizes from 0·3 to 0·7 for most domains. Patients in the ide-cel group showed statistically significant and clinically meaningful improvements across the primary PRO domains of interest, with the exception of QLQ-MY20 disease symptoms, side effects of treatment, and EQ-5D-5L index score, which showed improvement across assessment visits but did not exceed the within-group minimally important difference thresholds. The ide-cel group had shorter times to clinically meaningful improvement than the standard regimens group in QLQ-C30 domains except in role functioning, diarrhoea, and financial difficulties; in QLQ-MY20 domains except body image; and in EQ-5D-VAS. Ide-cel offers improved health-related quality of life compared with standard regimens for patients with relapsed and refractory multiple myeloma after previous lines of therapy. The PRO data highlight the extended QoL benefits of a one-time infusion with ide-cel compared with continuous treatment with standard regimens in the treatment of triple-class exposed patients with relapsed and refractory multiple myeloma. 2seventy bio and Celgene, a Bristol Myers Squibb Company.

中文翻译：

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使用 idecabtagene vicleucel 或标准方案治疗的三级暴露复发难治性多发性骨髓瘤患者的健康相关生活质量：来自 3 期、随机、开放标签 KarMMa-3 临床试验的患者报告结果

嵌合抗原受体 T 细胞疗法 idecabtagene vicleucel (ide-cel) 在正在进行的 3 期 KarMMa-3 试验中，与标准治疗方案相比，在先前接受过两到四种治疗方案的复发性难治性多发性骨髓瘤成人患者中表现出显着改善的无进展生存期()。本研究分析了患者报告的结果 (PRO)，这是 KarMMa-3 的次要终点。在随机、开放标签、3 期 KarMMa-3 试验中，386 名住院患者（年龄≥18 岁，患有可测量疾病，东部肿瘤合作组表现状态评分为 0 或 1，之前接受过 2 至 4 次治疗）方案（包括免疫调节剂、蛋白酶体抑制剂和 daratumumab），并在接受最后一次治疗的最后一剂后记录了疾病进展）被随机分配到 ide-cel (n=254) 或标准方案（daratumumab、pomalidomide 和 daratumumab）。地塞米松；达雷妥尤单抗、硼替佐米和地塞米松；伊沙佐米、来那度胺和地塞米松；卡非佐米和地塞米松；或埃罗妥珠单抗、泊马度胺和地塞米松；n=132)。患者应完成欧洲癌症研究与治疗组织 (EORTC) 生活质量 C30 问卷 (QLQ-C30)、多发性骨髓瘤模块 (QLQ-MY20)、EQ 5 维度 (EQ-5D) 和 EQ-5D基线和随访时间点的视觉模拟量表 (VAS)（数据截止日期为 2022 年 4 月 18 日）。PRO 包括九个预先指定的主要领域：EORTC QLQ-C30 GHS——生活质量 (QoL)、身体功能、认知功能、疲劳和疼痛；QLQ-MY20疾病症状及治疗副作用；以及五级EQ-5D（EQ-5D-5L）指数评分和EQ-5D视觉VAS。使用事后约束纵向数据分析来分析从基线到第 20 个月的总体最小二乘均值变化的差异。使用 Cox 比例风险模型分析确认相对于基线的改善或恶化的时间。患者在2019年5月6日至2022年4月8日之间被随机分配。总体而言，中位年龄为63岁（IQR 55-68）；151 名（39%）患者为女性；250 名（65%）名患者为白人，36 名（9%）名黑人或非裔美国人，19 名（5%）名西班牙裔或拉丁裔患者，12 名（3%）名亚裔患者，以及 7 名（2%）名其他种族患者。中位随访时间为 18·6 个月（IQR 14·0–26·4）。PRO 合规性自始至终高于 75%。总体最小二乘均值相对于基线的变化有利于 ide-cel，对于大多数领域，Hedges 的 g 效应大小从 0·3 到 0·7。ide-cel 组的患者在主要 PRO 感兴趣领域表现出统计学上显着且具有临床意义的改善，但 QLQ-MY20 疾病症状、治疗副作用和 EQ-5D-5L 指数评分除外，这些指标显示各方面均有改善评估访问，但没有超过组内最小重要差异阈值。除角色功能外，ide-cel 组在 QLQ-C30 领域中实现具有临床意义的改善的时间比标准方案组更短。腹泻和经济困难；在 QLQ-MY20 领域（身体图像除外）；以及 EQ-5D-VAS 中。与标准治疗方案相比，Ide-cel 为经过先前治疗的复发性和难治性多发性骨髓瘤患者提供了改善的健康相关生活质量。PRO 数据强调了在治疗三级暴露的复发性难治性多发性骨髓瘤患者中，与标准方案持续治疗相比，一次性输注 ide-cel 具有延长生活质量的益处。2seventy bio 和 Celgene（百时美施贵宝公司）。