Department of Critical Care, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
Clinical Pharmacy Specialist in Critical Care, Division of Pharmacy, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
Crit Care Med. 2022 Jan 1;50(1):81-92. doi: 10.1097/CCM.0000000000005149.
To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome.
Retrospective cohort study.
Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative.
Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019.
Demographics, toxicities, specific interventions, and outcomes were collected.
One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3-4 toxicities (66.7%); 15.2% had grade 3-4 cytokine release syndrome and 64% grade 3-4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64-not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival.
This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.
报告细胞因子释放综合征或免疫效应细胞相关神经毒性综合征后入住 ICU 的成年患者的流行病学、治疗方法和结局。
回顾性队列研究。
美国 9 个参与嵌合抗原受体-ICU 计划的中心。
2017 年 11 月至 2019 年 5 月期间接受嵌合抗原受体 T 细胞治疗并需要 ICU 入院的成年患者。
收集人口统计学、毒性、具体干预措施和结局数据。
在研究期间，105 例接受 axicabtagene ciloleucel 治疗的患者因细胞因子释放综合征或免疫效应细胞相关神经毒性综合征需要入住 ICU。在入住 ICU 时，大多数患者有 3-4 级毒性（66.7%）；15.2%有 3-4 级细胞因子释放综合征，64%有 3-4 级免疫效应细胞相关神经毒性综合征。在 ICU 期间，77.1%的患者出现细胞因子释放综合征，84.8%的患者出现免疫效应细胞相关神经毒性综合征；61.9%的患者同时出现两种毒性。79%的患者在 ICU 期间出现 3 级以上毒性，但血管加压药（18.1%）、机械通气（10.5%）和透析（2.9%）的需求并不常见。免疫效应细胞相关脑病评分小于 3（69.7%）、癫痫发作（20.2%）、癫痫持续状态（5.7%）、运动障碍（12.4%）和脑水肿（7.9%）更为常见。ICU 死亡率为 8.6%，仅有 3 例死亡与细胞因子释放综合征或免疫效应细胞相关神经毒性综合征有关。中位总生存时间为 10.4 个月（95%CI，6.64-未获得 mo）。毒性分级或器官支持对总生存无影响；累积皮质类固醇剂量越高，总生存和无进展生存时间越短。
这是第一项描述接受嵌合抗原受体 T 细胞治疗后因细胞因子释放综合征或免疫效应细胞相关神经毒性综合征而需要入住 ICU 的多中心患者队列的研究。尽管毒性严重，但该患者人群的器官支持和院内死亡率较低。
