Background

CAR-T cell (chimeric antigen receptor T) therapy has emerged as an effective treatment of refractory hematological malignancies. Intensive care management is intrinsic to CAR-T cell therapy. We aim to describe and to assess outcomes in critically ill CAR-T cell recipients.

Study design and methods

Hospital-wide retrospective study. Consecutive CAR-T cell recipients requiring ICU admission from July 2017 and December 2020 were included.

Results

71 patients (median age 60 years [37–68]) were admitted to the ICU 6 days [4–7] after CAR-T cell infusion. Underlying malignancies included diffuse large B cell lymphoma (n = 53, 75%), acute lymphoblastic leukemia (17 patients, 24%) and multiple myeloma (n = 1, 1.45%). Performance status (PS) was 1 [1–2]. Shock was the main reason for ICU admission (n = 40, 48%). Isolated cytokine release syndrome (CRS) was the most common complication (n = 33, 46%), while 21 patients (30%) had microbiologically documented bacterial infection (chiefly catheter-related infection). Immune effector cell-associated neurotoxicity syndrome was reported in 26 (37%) patients. At ICU admission, vasopressors were required in 18 patients (25%) and invasive mechanical ventilation in two. Overall, 49 (69%) and 40 patients (56%) received tocilizumab or steroids, respectively.

Determinant of mortality were the reason for ICU admission (disease progression vs. sepsis or CRS (HR 4.02 [95%CI 1.10–14.65]), Performance status (HR 1.97/point [95%CI 1.14–3.41]) and SOFA score (HR 1.16/point [95%CI 1.01–1.33]).

Conclusions

Meaningful survival could be achieved in up to half the CAR-T cell recipients. The severity of organ dysfunction is a major determinant of death, especially in patients with altered performance status or disease progression.

中文翻译：

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ICU 资源在 CAR-T 细胞受者中的使用：一项全院范围的研究

背景

CAR-T细胞（嵌合抗原受体T）疗法已成为难治性血液系统恶性肿瘤的有效治疗方法。重症监护管理是 CAR-T 细胞疗法所固有的。我们旨在描述和评估危重 CAR-T 细胞受体的结果。

研究设计和方法

医院范围的回顾性研究。包括从 2017 年 7 月和 2020 年 12 月起需要入住 ICU 的连续 CAR-T 细胞受体。

结果

71 名患者（中位年龄 60 岁 [37-68]）在 CAR-T 细胞输注后 6 天 [4-7] 入住 ICU。潜在的恶性肿瘤包括弥漫性大 B 细胞淋巴瘤 ( n  = 53, 75%)、急性淋巴细胞白血病 (17 例, 24%) 和多发性骨髓瘤 ( n  = 1, 1.45%)。性能状态 (PS) 为 1 [1-2]。休克是入住 ICU 的主要原因（n  = 40, 48%）。孤立性细胞因子释放综合征 (CRS) 是最常见的并发症 ( n = 33, 46%)，而 21 名患者 (30%) 有微生物学记录的细菌感染（主要是导管相关感染）。在 26 名 (37%) 患者中报告了免疫效应细胞相关的神经毒性综合征。入住 ICU 时，18 名患者 (25%) 需要血管加压药，2 名患者需要有创机械通气。总体而言，分别有 49 名 (69%) 和 40 名 (56%) 患者接受了托珠单抗或类固醇治疗。

死亡率的决定因素是入住 ICU 的原因（疾病进展与败血症或 CRS（HR 4.02 [95%CI 1.10–14.65]）、体能状态（HR 1.97/点 [95%CI 1.14–3.41]）和 SOFA 评分（ HR 1.16/点 [95%CI 1.01–1.33]）。

结论

多达一半的 CAR-T 细胞受体可以实现有意义的生存。器官功能障碍的严重程度是死亡的主要决定因素，特别是在体能状态改变或疾病进展的患者中。