Early detection of chimeric antigen receptor-T-associated neurotoxicity via cytokine monitoring in serum.

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common and life-threatening complication of chimeric antigen receptor (CAR) T-cell therapy, with early detection being critical for timely intervention and improved outcomes. Cytokines such as interleukin-6 (IL-6) are key mediators of the inflammatory cascade underlying ICANS pathogenesis, but prospective clinical evidence establishing whether serial IL-6 elevations precede ICANS onset remains limited. Here we quantify IL-6 levels in a prospective cohort of 40 CAR-T patients (270 serum samples), using a simple in-house microfluidic bead immunoassay. IL-6 levels measured by our assay were significantly associated with next-day ICANS onset. In a generalized estimating equation model adjusted for concurrent cytokine release syndrome grade, each ∼3.4-fold increase in IL-6 levels was linked to a 76% increase in the odds of ICANS onset the following day, independent of other clinical variables. Overall, we show the temporal association of IL-6 with next-day ICANS onset, demonstrate the potential of frequent cytokine measurement to guide CAR-T patient management and develop a simple experimental method to perform such monitoring.