10.04.22

Biomarkers of Severe CRS and ICANS in B-ALL patients

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 new study found preinfusion biomarkers predictive of severe cytokine release syndrome (CRS) in patients being treated for B-cell acute lymphoblastic leukemia (B-ALL). Researchers studied a sample of pediatric trial participants with B-ALL for clues about CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) — complications that can arise after chimeric antigen T-cell (CAR T) immunotherapy. The children had been treated with CAR T CTL019, which targets CD19, as part of two clinical investigations. Using comprehensive proteomic profiling, researchers measured more than 1,400 serum proteins at different time intervals. From this data, they identified fms-like tyrosine kinase 3 (FLT3) and mast cell immunoglobulin-like receptor 1 (MILR1) as preinfusion biomarkers that can predict severe CRS with a previously unseen level of sensitivity, specificity, and accuracy. A further discovery clarifying the role of the IFNy pathway in CRS had important implications for treatment. Additionally, the work suggested that IL18 plays a part in ICANS and that exploring the value of IL18 inhibitors in clinical trials is worthwhile.


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