ABSTRACT

Introduction

Chimeric antigen receptor (CAR)-T-cell therapy is a new treatment for patients with hematologic malignancies in which other therapies have failed.

Areas covered

The review provides an overview for recognizing and managing the most acute toxicities related to CAR-T cells.

Expert opinion

The development of immune-mediated toxicities is a common challenge of CAR-T therapy. The mechanism that determines this toxicity is still unclear, although an unfavorable tumor microenvironment and a pro-inflammatory state put patients at risk. The monitoring, diagnosis, and treatment of post-CAR-T toxicities must be determined and based on international guidelines and internal clinical practice. It is urgent to identify biomarkers that can identify patients at greater risk of developing complications. The adoption of consistent grading criteria is necessary to improve toxicity management strategies continually. The first-line therapy consists of supportive care and treatment with tocilizumab or corticosteroids. An early start of cytokine blockade therapies could mitigate toxicity. The plan will include cytokine release prophylaxis, a risk-adapted treatment, prevention of on-target/off-tumor effect, and a switch on/off CAR-T approach.

中文翻译：

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识别和管理 CAR-T 细胞介导的毒性：代表意大利 CAR-T 多学科团队

摘要

介绍

嵌合抗原受体 (CAR)-T 细胞疗法是一种新的治疗方法，用于治疗其他疗法失败的恶性血液病患者。

涵盖的领域

该综述概述了识别和管理与 CAR-T 细胞相关的最急性毒性。

专家意见

免疫介导毒性的发展是 CAR-T 疗法的共同挑战。尽管不利的肿瘤微环境和促炎状态使患者处于危险之中，但决定这种毒性的机制仍不清楚。CAR-T 后毒性的监测、诊断和治疗必须根据国际指南和内部临床实践来确定。迫切需要确定能够识别出并发症风险更大的患者的生物标志物。采用一致的分级标准对于不断改进毒性管理策略是必要的。一线治疗包括支持治疗和托珠单抗或皮质类固醇治疗。细胞因子阻断疗法的早期开始可以减轻毒性。该计划将包括细胞因子释放预防，