Biomarkers for Predicting Cytokine Release Syndrome following CD19-Targeted CAR T Cell Therapy

Abstract Chimeric Ag receptor (CAR) T cell therapy has shown astonishing potency in treating a variety of hematological malignancies in recent years. Along with this lifesaving potential comes the life-threatening toxicities of cytokine release syndrome (CRS) and neurotoxicity. This work seeks to consolidate biomarker candidates with the potential to predict the severity of CRS and neurotoxicity in patients receiving CD19-targeted CAR T cell therapy. In this systematic review, 33 clinical trials were evaluated for biomarkers that can predict the severity of posttreatment CRS and neurotoxicity. CRS and neurotoxicity occurred in 73.4 and 37% of the reviewed patients, respectively. Identified biomarker candidates included tumor burden, platelet count, C-reactive protein, ferritin, IFN-γ, IL-2, IL-6, IL-8, IL-10, IL-15, and TGF-β. Combinatorial algorithms based on cytokine levels and clinical parameters show excellent promise in predicting CAR-T-cell-therapy–associated toxicities, with improved accuracy over the component biomarkers.