来那度胺难治性多发性骨髓瘤患者接受西达基奥仑赛或标准治疗后的患者报告结局（CARTITUDE-4）：一项随机、开放标签的3期试验结果

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.

作者信息

Mina Roberto, Mylin Anne K, Yokoyama Hisayuki, Magen Hila, Alsdorf Winfried, Minnema Monique C, Shune Leyla, Isufi Iris, Harrison Simon J, Shah Urvi A, Schecter Jordan M, Vogel Martin, Lendvai Nikoletta, Gries Katharine S, Katz Eva G, Slaughter Ana, Lonardi Carolina, Gilbert Jane, Li Quanlin, Deraedt William, Filho Octavio Costa, Patel Nitin, Florendo Erika, Karlin Lionel, Weisel Katja

机构信息

Division of Hematology, Azienda Ospedaliero Universitaria Cittá della Salute e della Scienza di Torino, Torino, Italy.

Department of Haematology, Rigshospitalet, Copenhagen, Denmark.

出版信息

Lancet Haematol. 2025 Jan;12(1):e45-e56. doi: 10.1016/S2352-3026(24)00320-X.

DOI:10.1016/S2352-3026(24)00320-X

PMID:39756844

Abstract

BACKGROUND

In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes.

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 × 10 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone). 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. 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-treat population) and EuroQol 5-Dimension 5-Level (EQ-5D-5L; intention-to-treat population). This study is registered with ClinicalTrials.gov number NCT04181827 and is ongoing.

FINDINGS

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. MySIm-Q compliance post-baseline was 70 to 81% (cilta-cel) and 79 to 89% (standard of care). 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). Rates of clinically meaningful improvements in GHS and VAS were higher with cilta-cel than with standard of care.

INTERPRETATION

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

FUNDING

Janssen Research & Development, Legend Biotech USA.

摘要

背景

在CARTITUDE-4研究中，与复发、来那度胺难治性多发性骨髓瘤患者的标准治疗相比，西达基奥仑赛（cilta-cel）显著改善了无进展生存期（主要终点；先前已报道）。我们在此报告患者报告的结局。

方法

在正在进行的3期开放标签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随机分配至西达基奥仑赛组（目标剂量，0·75×10 CAR-T细胞/kg）或标准治疗组（达雷妥尤单抗、泊马度胺和地塞米松；泊马度胺、硼替佐米和地塞米松）。符合条件的患者患有复发、来那度胺难治性多发性骨髓瘤，接受过1至3线先前治疗，包括蛋白酶体抑制剂和免疫调节药物，且东部肿瘤协作组（ECOG）体能状态为0或1。此处报告的次要终点包括症状持续恶化时间（多发性骨髓瘤症状与影响问卷[MySIm-Q]；关键次要终点）以及欧洲癌症研究与治疗组织（EORTC）生活质量（QoL）问卷核心C30（意向性治疗人群）和欧洲五维健康量表（EQ-5D-5L；意向性治疗人群）的变化。本研究已在ClinicalTrials.gov注册，注册号为NCT04181827，正在进行中。

研究结果

患者于2020年7月10日至2021年11月17日入组，516例筛查患者中的419例被随机分配（西达基奥仑赛组，n = 208；标准治疗组，n = 211；中位随访时间，15·9个月[IQR 12·4至17·8]）；中位年龄为61岁。西达基奥仑赛组208例患者中的191例（92%）和标准治疗组209例可评估患者中的190例（91%）完成了基线评估。基线后MySIm-Q的依从率为70%至81%（西达基奥仑赛组）和79%至89%（标准治疗组）。西达基奥仑赛组与标准治疗组相比，MySIm-Q症状持续恶化的中位时间分别为23·7个月和18·9个月（HR 0·42；95% CI 0·26至0·68）。EORTC总体健康状况（GHS）的12个月平均变化分别为+10·1（95% CI 7·0至13·1）分和 -1·5（95% CI -5·3至2·3）分，EQ-5D-5L视觉模拟量表（VAS）的变化分别为+8·0（95% CI 5·2至10·7）分和+1·4（95% CI -1·9至4·7）分。西达基奥仑赛组GHS和VAS具有临床意义的改善率高于标准治疗组。