Mitigation and Management of Common Toxicities Associated with the Administration of CAR-T Therapies in Oncology Patients.

Abstract

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.