Diorio C, Shraim R, Myers R, et al. Comprehensive Serum Proteome Profiling of Cytokine Release Syndrome and Immune Effector Cell–Associated Neurotoxicity Syndrome Patients with B-Cell ALL Receiving CAR T19. Clinical Cancer Research. 2022; (doi: 10.1158/1078-0432.CCR-22-0822).
A recent study identified pre-infusion biomarkers for forecasting severe cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) in children after chimeric antigen receptor T-cell (CAR T) treatment. The findings demonstrate improved sensitivity, specificity, and accuracy compared with the current disease burden benchmark. Researchers used proteomic profiling to evaluate more than 1,400 serum proteins over multiple time periods in patients with B-cell acute lymphoblastic leukemia who were treated with the CD19-targeted CAR T CTL019 in two clinical trials. FMS-like tyrosine kinase 3 (FLT3) and mast cell immunoglobulin-like receptor 1 (MILR1) were identified as pre-infusion predictive biomarkers of severe CRS. The condition was characterized as an interferon gamma-driven process with a protein signature that overlaps hemophagocytic lymphohistiocytosis (HLH), rather than occurring separately. Researchers found interleukin-18 to be a potentially targetable cytokine associated with development of ICANS.