Tisagenlecleucel Model-Based Cellular Kinetic Analysis of Chimeric Antigen Receptor-T Cells.
Andrew M SteinStephan A GruppJohn E LevineTheodore W LaetschMichael A PulsipherMichael W BoyerKeith J AugustBruce L LevineLori TomassianSweta ShahMimi LeungPai-Hsi HuangRakesh AwasthiKaren Thudium MuellerPatricia A WoodCarl H JunePublished in: CPT: pharmacometrics & systems pharmacology (2019)
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.
Keyphrases
- cell therapy
- acute lymphoblastic leukemia
- phase ii
- stem cells
- rheumatoid arthritis
- mesenchymal stem cells
- clinical trial
- young adults
- physical activity
- juvenile idiopathic arthritis
- acute myeloid leukemia
- case report
- rheumatoid arthritis patients
- allogeneic hematopoietic stem cell transplantation
- case control
- randomized controlled trial
- electronic health record
- diffuse large b cell lymphoma
- multiple myeloma
- current status
- big data
- hodgkin lymphoma
- bone marrow
- disease activity
- data analysis
- childhood cancer