Renninger Jonathan, Kurz Lisa, Stein Heather
GSK Safety Evaluation and Risk Management, Global Safety, Philadelphia, PA, USA.
GSK Safety Evaluation and Risk Management, Global Safety, Upper Providence, PA, USA.
Drug Saf. 2025 Mar 19. doi: 10.1007/s40264-025-01538-5.
Chimeric antigen receptor T-cell (CAR-T) therapies are one of the main approaches among targeted cellular therapies. Despite the potential benefit and durable responses observed in some patients receiving CAR-T therapies, serious and potentially fatal toxicities remain a major challenge. The most common CAR-T-associated toxicities include cytokine release syndrome (CRS), neurotoxicity, cytopenias, and infections. While CRS and neurotoxicity are generally managed with tocilizumab and corticosteroids, respectively, high-grade toxicities can be life-threatening. Close postinfusion monitoring and assessment of clinical laboratory parameters, patient-related and clinical risk factors (e.g., age, tumor burden, comorbidities, baseline laboratory parameters, and underlying abnormalities), and therapy-related risk factors (e.g., CAR-T type, dose, and CAR-T-induced toxicity) are effective strategies to mitigate the toxicities. Clinical laboratory parameters, including various cytokines, have been identified for CRS (interleukin [IL]-1, IL-2, IL-5, IL-6, IL-8, IL-10, C-reactive protein [CRP], interferon [IFN]-γ, ferritin, granulocyte-macrophage colony-stimulating factor [GM-CSF], and monocyte chemoattractant protein-1), neurotoxicity (IL-1, IL-2, IL-6, IL-15, tumor necrosis factor [TNF]-α, GM-CSF, and IFN-γ), cytopenias (IL-2, IL-4, IL-6, IL-10, IFN-γ, ferritin, and CRP), and infections (IL-8, IL-1β, CRP, IFN-γ, and procalcitonin). CAR-T-associated toxicities can be monitored and treated to mitigate the risk to patients. Assessment of alterations in clinical laboratory parameter values that are correlated with CAR-T-associated toxicities may predict development and/or severity of a given toxicity, which can improve patient management strategies and ultimately enable the patients to better tolerate these therapies.
嵌合抗原受体T细胞(CAR-T)疗法是靶向细胞疗法的主要方法之一。尽管在一些接受CAR-T疗法的患者中观察到了潜在益处和持久反应,但严重且可能致命的毒性仍然是一个重大挑战。最常见的与CAR-T相关的毒性包括细胞因子释放综合征(CRS)、神经毒性、血细胞减少和感染。虽然CRS和神经毒性通常分别用托珠单抗和皮质类固醇进行处理,但高级别毒性可能危及生命。输注后密切监测和评估临床实验室参数、患者相关和临床风险因素(如年龄、肿瘤负荷、合并症、基线实验室参数和潜在异常)以及治疗相关风险因素(如CAR-T类型、剂量和CAR-T诱导的毒性)是减轻毒性的有效策略。临床实验室参数,包括各种细胞因子,已被确定与CRS(白细胞介素[IL]-1、IL-2、IL-5、IL-6、IL-8、IL-10、C反应蛋白[CRP]、干扰素[IFN]-γ、铁蛋白、粒细胞-巨噬细胞集落刺激因子[GM-CSF]和单核细胞趋化蛋白-1)、神经毒性(IL-1、IL-2、IL-6、IL-15、肿瘤坏死因子[TNF]-α、GM-CSF和IFN-γ)、血细胞减少(IL-2、IL-4、IL-6、IL-10、IFN-γ、铁蛋白和CRP)以及感染(IL-8、IL-1β、CRP、IFN-γ和降钙素原)相关。与CAR-T相关的毒性可以进行监测和治疗,以降低对患者的风险。评估与CAR-T相关毒性相关的临床实验室参数值的变化可能预测特定毒性的发生和/或严重程度,这可以改善患者管理策略,并最终使患者能够更好地耐受这些疗法。
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