Tisagenlecleucel Model‐Based Cellular Kinetic Analysis of Chimeric Antigen Receptor–T Cells
Year: 2019
Type: article
Abstract: 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.
DOI: 10.1002/psp4.12388
Institutions: Children's Hospital of Philadelphia, University of Pennsylvania, University of Michigan, Icahn School of Medicine at Mount Sinai, The University of Texas Southwestern Medical Center, University of Southern California, Children's Hospital of Los Angeles, University of Utah, Children's Mercy Hospital, Novartis (United States), Novartis Institutes for BioMedical Research
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
OpenAlex ID: W2921490864