Tisagenlecleucel Model‐Based Cellular Kinetic Analysis of Chimeric Antigen Receptor–T Cells

Autor: Andrew M. Stein, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith J. August, Bruce L. Levine, Lori Tomassian, Sweta Shah, Mimi Leung, Pai‐Hsi Huang, Rakesh Awasthi, Karen Thudium Mueller, Patricia A. Wood, Carl H. June
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: CPT: Pharmacometrics & Systems Pharmacology, Vol 8, Iss 5, Pp 285-295 (2019)
Druh dokumentu: article
ISSN: 2163-8306
DOI: 10.1002/psp4.12388
Popis: 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.
Databáze: Directory of Open Access Journals
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