嵌合抗原受体 T 细胞治疗后入住重症监护病房（CARTTAS）患者的结局：一项国际多中心观察性队列研究。

Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study.

机构信息

Critical Care Department, APHP, Hôpital Saint-Louis, University of Paris, Paris, France.

Medical Intensive Care Unit, Hospital Clínic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

出版信息

Lancet Haematol. 2021 May;8(5):e355-e364. doi: 10.1016/S2352-3026(21)00060-0.

DOI:10.1016/S2352-3026(21)00060-0

PMID:33894170

Abstract

BACKGROUND

Chimeric antigen receptor (CAR) T-cell therapy can induce side-effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), which often require intensive care unit admission. The aim of this study was to describe management of critically ill CAR T-cell recipients in intensive care.

METHODS

This international, multicentre, observational cohort study was done in 21 intensive care units in France, Spain, the USA, the UK, Russia, Canada, Germany, and Austria. Eligible patients were aged 18 years or older; had received CAR T-cell therapy in the past 30 days; and had been admitted to intensive care for any reason. Investigators retrospectively included patients admitted between Feb 1, 2018, and Feb 1, 2019, and prospectively included patients admitted between March 1, 2019, and Feb 1, 2020. Demographic, clinical, laboratory, treatment, and outcome data were extracted from medical records. The primary endpoint was 90-day mortality. Factors associated with mortality were identified using a Cox proportional hazard model.

FINDINGS

942 patients received CAR T-cell therapy, of whom 258 (27%) required admission to intensive care and 241 (26%) were included in the analysis. Admission to intensive care was needed within median 4·5 days (IQR 2·0-7·0) of CAR T-cell infusion. 90-day mortality was 22·4% (95% CI 17·1-27·7; 54 deaths). At initial evaluation on admission, isolated cytokine release syndrome was identified in 101 patients (42%), cytokine release syndrome and ICANS in 93 (39%), and isolated ICANS in seven (3%) patients. Grade 3-4 cytokine release syndrome within 1 day of admission to intensive care was found in 50 (25%) of 200 patients and grade 3-4 ICANS in 38 (35%) of 108 patients. Bacterial infection developed in 30 (12%) patients. Life-saving treatments were used in 75 (31%) patients within 24 h of admission to intensive care, primarily vasoactive drugs in 65 (27%) patients. Factors independently associated with 90-day mortality by multivariable analysis were frailty (hazard ratio 2·51 [95% CI 1·37-4·57]), bacterial infection (2·12 [1·11-4·08]), and lifesaving therapy within 24 h of admission (1·80 [1·05-3·10]).

INTERPRETATION

Critical care management is an integral part of CAR T-cell therapy and should be standardised. Studies to improve infection prevention and treatment in these high-risk patients are warranted.

FUNDING

Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique.

摘要

背景

嵌合抗原受体（CAR）T 细胞疗法可引发细胞因子释放综合征和免疫效应细胞相关神经毒性综合征（ICANS）等副作用，这些副作用通常需要入住重症监护病房。本研究旨在描述重症 CAR T 细胞受者在重症监护病房的管理情况。

方法

这是一项在法国、西班牙、美国、英国、俄罗斯、加拿大、德国和奥地利的 21 个重症监护病房进行的国际性、多中心、观察性队列研究。纳入标准为：年龄≥18 岁；过去 30 天内接受过 CAR T 细胞治疗；因任何原因入住重症监护病房。研究者回顾性纳入了 2018 年 2 月 1 日至 2019 年 2 月 1 日期间入院的患者，并前瞻性纳入了 2019 年 3 月 1 日至 2020 年 2 月 1 日期间入院的患者。从病历中提取人口统计学、临床、实验室、治疗和结局数据。主要终点为 90 天死亡率。使用 Cox 比例风险模型确定与死亡率相关的因素。

结果

942 例患者接受了 CAR T 细胞治疗，其中 258 例（27%）需要入住重症监护病房，241 例（26%）被纳入分析。CAR T 细胞输注后中位 4.5 天（IQR 2.0-7.0）需要入住重症监护病房。90 天死亡率为 22.4%（95%CI 17.1-27.7；54 例死亡）。入院时初始评估发现，101 例（42%）患者存在单纯细胞因子释放综合征，93 例（39%）患者存在细胞因子释放综合征和 ICANS，7 例（3%）患者存在单纯 ICANS。200 例患者中，50 例（25%）在入住重症监护病房后 1 天内出现 3-4 级细胞因子释放综合征，108 例患者中 38 例（35%）出现 3-4 级 ICANS。30 例（12%）患者发生细菌感染。75 例（31%）患者在入住重症监护病房后 24 小时内接受了救命治疗，其中 65 例（27%）患者使用了血管活性药物。多变量分析显示，90 天死亡率的独立相关因素为虚弱（HR 2.51 [95%CI 1.37-4.57]）、细菌感染（2.12 [1.11-4.08]）和入住重症监护病房后 24 小时内接受救命治疗（1.80 [1.05-3.10]）。