Cytokines could predict risk of CAR T neurotoxicities

In a paper published in Cancer Discovery, researchers at the Fred Hutchinson Cancer Research Center and colleagues found that the IL-6 and monocyte chemoattractant protein-1 (MCP-1; CCL2) cytokines could act as early biomarkers along with high fever to determine which patients treated with chimeric antigen receptor (CAR) T therapies will develop life-threatening neurotoxicities.

In a Phase I/II trial in 133 patients with relapsed/refractory, CD19-positive B cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL) who were receiving lymphodepletion chemotherapy and CD19 CAR T cells, 53 patients developed neurotoxicity within 28 days, with 7 patients developing neurotoxicity of grade 4 or higher. The researchers analyzed the patients' characteristics to identify factors associated with an increased risk of neurotoxicity and found that grade >4 neurotoxicity occurred in all patients displaying a fever of 38.9°C or higher, elevated serum IL-6 levels, and elevated MCP-1 levels within 36 hours of CAR T cell infusion. The predictive model had a sensitivity of 100% and specificity of 94%...