From the Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Anesth Analg. 2019 Aug;129(2):434-441. doi: 10.1213/ANE.0000000000004201.
Cancer immunotherapy has entered a new era with the recent introduction of genetically engineered T-cells that express chimeric antigen receptors (CARs) capable of recognizing and destroying tumor cells. Several clinical trials in patients with relapsed or refractory B-cell malignancies have demonstrated complete remission rates ranging from 50% to 90%, with long-term data suggestive of a possible curative response. CAR T-cell therapy is currently under investigation for earlier use in these disease processes and in various other solid and liquid tumors. CAR T-cell therapy is associated with a unique postinfusion toxicity profile including cytokine-release syndrome and neurotoxicity. These toxicities are usually reversible but can be fatal, requiring close vigilance and prompt treatment often in an intensive care unit (ICU) setting. CAR T-cell therapy is currently restricted to designated centers possessing expertise in acute toxicity management, but wider use is likely if early therapeutic successes are replicated. As perioperative and critical care physicians, anesthesiologists may encounter such patients in the perioperative or ICU setting and should become familiar with this unique and novel therapeutic modality capable of causing extreme cardiovascular and respiratory compromise. This review will describe the immunobiology of CAR T-cells, their relevance to cancer treatment, clinical aspects of their therapeutic use in cancer chemotherapy, toxicities related to CAR T-cell use, and their therapeutic management.
癌症免疫疗法已经进入了一个新时代,最近引入了经过基因工程改造的 T 细胞,这些 T 细胞能够表达嵌合抗原受体 (CAR),从而能够识别和摧毁肿瘤细胞。几项针对复发或难治性 B 细胞恶性肿瘤患者的临床试验表明,完全缓解率在 50%至 90%之间,长期数据表明可能有治愈反应。目前正在研究 CAR T 细胞疗法,以便更早地用于这些疾病过程以及各种其他实体瘤和液体瘤。CAR T 细胞疗法与独特的输注后毒性特征相关,包括细胞因子释放综合征和神经毒性。这些毒性通常是可逆的,但可能是致命的,需要密切监测并及时治疗,通常在重症监护病房 (ICU) 环境中进行。CAR T 细胞疗法目前仅限于拥有急性毒性管理专业知识的指定中心,但如果早期治疗成功得到复制,其使用范围可能会更广。作为围手术期和重症监护医生,麻醉师可能会在围手术期或 ICU 环境中遇到此类患者,并且应该熟悉这种能够引起极端心血管和呼吸系统损害的独特新型治疗方式。本文将描述 CAR T 细胞的免疫生物学、它们在癌症治疗中的相关性、它们在癌症化疗中的治疗用途的临床方面、与 CAR T 细胞使用相关的毒性以及它们的治疗管理。