P1442: DYNAMIC LANDSCAPE OF PLASMA PROTEOME AND METABOLOME IN B-ALL PATIENTS DURING CAR-T CELL THERAPY

Abstract

Background: Poor understanding of plasma proteomic and metabolomic features during chimeric antigen receptor (CAR) T cell therapy may affect the exploitation of therapeutic potential in the management of hematological malignancies. Aims: This word was designed to illustrate the dynamic landscape of plasma proteome and metabolome in B-ALL patients during CAR-T cell therapy and detailed the kinetics of proteins and metabolites during cytokines storm. Methods: In this study, we performed proteomic and metabolomic profiling of plasma from 20 patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) on CAR-T cell therapy and 22 healthy controls. Results: We identified molecular changes in the plasma of B-ALL patients compared to healthy controls. Many of the changes involved actin cytoskeleton organization, acute-phase responses, autophagy, branched-chain amino acid, and lipid metabolism (Figure A). Furthermore, CAR-T cell therapy reshaped plasma proteome and metabolome with discrete kinetics, as represented by upregulated acute-phase response and triglycerides metabolism and downregulated actin cytoskeleton organization, axon extension, retrograde endocannabinoid signaling, autophagy, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis during the therapy (Figure B). Moreover, we identified sets of covarying molecules involved in the acute inflammatory response, epithelial-mesenchymal transition, glutathione metabolism, and tryptophan metabolism and change in concert with the dynamics of circulating IL-6 in patients with cytokines storm (Figure C). Subgroup analysis further revealed numerous prognostic biomarkers, such as proteins related to allograft rejection, which were down-regulated in patients who achieved stable complete remission. Image:Summary/Conclusion: This study provided a dynamic landscape of plasma proteome and metabolome in B-ALL patients during CAR-T cell therapy and offered novel insights into the pathogenesis of B-ALL and CAR-T cell therapy-related toxicities.