肿瘤患者 CAR-T 治疗给药相关常见毒性的减轻与管理

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]- , 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]- , GM-CSF, and IFN- ), cytopenias (IL-2, IL-4, IL-6, IL-10, IFN- , ferritin, and CRP), and infections (IL-8, IL-1 , CRP, IFN- , 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. Chimeric antigen receptor T-cell (CAR-T) therapies are used in the treatment of various aggressive blood cancers. These therapies use a patient s immune cells (T cells) that are genetically modified to fight cancer.

In this article, we focus on the adverse effects associated with CAR-T therapies and discuss how they can be managed. The most common CAR-T-associated adverse effects include cytokine release syndrome (a rapid release of signaling proteins [cytokines] from affected immune cells), neurotoxicity (toxic effects on the nervous system), cytopenias (lower-than-normal blood cell levels), and infections.

Patients receiving CAR-T therapies need to be closely monitored for signs of any adverse effects. Some of these effects can be prevented or treated with medications.

However, current efforts focus on making the adverse effects less severe, and on identifying risk factors that may predict the likelihood and onset of a potential adverse effect. When an adverse effect occurs, the levels of certain molecules in the blood change. These changes can help physicians determine the type of adverse effect and select the best treatment to combat it. Some patient features (e. g.

, age, medical conditions, the size and spread of the tumor, and levels of certain molecules in the blood) and treatment-related factors (e. g. , therapy type and dose) should be considered before starting a CAR-T therapy. Adverse effects are monitored and treated to reduce the risk to patients. Evaluating the levels of certain parameters in the blood can improve patient management strategies and help patients better tolerate CAR-T therapies.