Immunological response to chimeric antigen receptor T-cell therapy in pediatric relapsed/refractory acute lymphoblastic leukemia: peak of cytokine levels on day 4 post-infusion

Chimeric antigen receptor (CAR) T-cell therapy is associated with specific toxicities related to immunological response to the therapy. The aim of the study was to analyze the kinetics of cytokine responses after CAR T-cell infusion and its correlation with observed toxicities. Data from patients treated with CAR T-cell therapy at a single children oncology center in period from 05.2023 to 08.2024 was analyzed. The data included CAR T-cell count in peripheral blood, hematology laboratory data and proinflammatory biomarkers (IL2, IL4, IL6, IL10, IL17A, TNFα, IFNγ, CRP, ferritin) and observed toxicities. Six patients were treated with CD19 CAR-T cell therapy for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). The expansion of CAR-T cells was observed during the first 14 days following infusion, with the peak occurring between days 6 and 12. Cytokine release syndrome was observed in 5 of 6 analyzed cases, mostly during first week after the infusion. An increase plasma concentration of IL2, IL10, and IFNγ was observed on the fourth day after CAR-T cell infusion. Biphasic peaks were detected in the plasma concentrations of I-4 (on 1 and 4 day), IL6 and IL17a (first days after infusion and day 8 and 9). Day 4 post-infusion was characterized by elevated plasma levels of most of the analyzed cytokines and it was timely related to CRS and ICANS. We also observed an immunological response to the infusion itself, along with CAR-T cell expansion.