Neurotoxicity after CTL019 in a pediatric and young adult cohort

ObjectiveTo characterize the incidence and clinical characteristics of neurotoxicity in the month following CTL019 infusion in children and young adults, to define the relationship between neurotoxicity and cytokine release syndrome (CRS), and to identify predictive biomarkers for development of neurotoxicity following CTL019 infusion.MethodsWe analyzed data on 51 subjects, 4 to 22 years old, who received CTL019, a chimeric antigen receptor –modified T‐cell therapy against CD19, between January 1, 2010 and December 1, 2015 through a safety/feasibility clinical trial (NCT01626495) at our institution. We recorded incidence of significant neurotoxicity (encephalopathy, seizures, and focal deficits) and CRS, and compared serum cytokine levels in the first month postinfusion between subjects who did and did not develop neurotoxicity.ResultsNeurotoxicity occurred in 23 of 51 subjects (45%, 95% confidence interval  = 31–60%) and was positively associated with higher CRS grade (p <  0.0001) but was not associated with demographic characteristics or prior oncologic treatment history. Serum interleukin (IL)‐2, IL‐15, soluble IL‐4, and hepatocyte growth factor concentrations were higher in subjects with neurotoxicity than those with isolated CRS. Differences in peak level s of select cytokines including IL‐12 and soluble tumor necrosis factor receptor‐1 within the first 3 days were seen in subjects with neurotoxicity.InterpretationNeurotoxicity is common after...
Source: Annals of Neurology - Category: Neurology Authors: Tags: Research Article Source Type: research