Document Type
Article
Publication Date
5-2019
Identifier
DOI: 10.1002/psp4.12388; PMCID: PMC6539725
Abstract
Tisagenlecleucel is a chimeric antigen receptor-T cell therapy that facilitates the killing of CD19+ B cells. A model was developed for the kinetics of tisagenlecleucel and the impact of therapies for treating cytokine release syndrome (tocilizumab and corticosteroids) on expansion. Data from two phase II studies in pediatric and young adult relapsed/refractory B cell acute lymphoblastic leukemia were pooled to evaluate this model and evaluate extrinsic and intrinsic factors that may impact the extent of tisagenlecleucel expansion. The doubling time, initial decline half-life, and terminal half-life for tisagenlecleucel were 0.78, 4.3, and 220 days, respectively. No impact of tocilizumab or corticosteroids on the expansion rate was observed. This work represents the first mixed-effect model-based analysis of chimeric antigen receptor-T cell therapy and may be clinically impactful as future studies examine prophylactic interventions in patients at risk of higher grade cytokine release syndrome and the effects of these interventions on chimeric antigen receptor-T cell expansion.
Journal Title
CPT Pharmacometrics Syst Pharmacol
Volume
8
Issue
5
First Page
285
Last Page
295
MeSH Keywords
Adolescent; Adult; Antibodies, Monoclonal, Humanized; Child; Child, Preschool; Clinical Trials, Phase II as Topic; Female; Half-Life; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Male; Models, Theoretical; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell; Young Adult
Keywords
Adolescent; Adult; Antibodies, Monoclonal, Humanized; Child; Child, Preschool; Clinical Trials, Phase II as Topic; Female; Half-Life; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Male; Models, Theoretical; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell; Young Adult
Recommended Citation
Stein AM, Grupp SA, Levine JE, et al. Tisagenlecleucel Model-Based Cellular Kinetic Analysis of Chimeric Antigen Receptor-T Cells. CPT Pharmacometrics Syst Pharmacol. 2019;8(5):285-295. doi:10.1002/psp4.12388
Comments
Grant support
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Publisher's Link: https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/psp4.12388