Clinical Pharmacology – Biomolecular
2019 PharmSci 360
Dosing Approaches for Novel Therapeutic Modalities - CAR-T Therapies.
A safe and efficacious dose of chimeric antigen receptor (CAR) T cells is not well defined and varies across CAR-T platforms. How dosing of the CAR-T therapy tisagenlecleucel relates to exposure, efficacy, and safety was explored in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and, diffuse large B-cell lymphoma (DLBCL). Logistic regression models were used to explore the relationship between dose and response and between dose and safety endpoints (incidence of cytokine release syndrome (CRS) and neurological toxicity). Scatter plots and regression was used to explore the relationship between dose and exposure and between dose and product attributes. The results and impact of these analyses will be presented. Recommended dose ranges were established for each indication based on the analyses between dose and exposure, efficacy, and safety endpoints.
Reference: Rakesh Awasthi, Karen Thudium Mueller, Gregory A. Yanik, Constantine S. Tam, Susana Rives, Joseph P. McGuirk, Michael W. Boyer, Ulrich Jäger, André Baruchel, Gary Douglas Myers, Peter Borchmann, Samantha M. Jaglowski, Heather E. Stefanski, Michael R. Bishop, Edward R. Waldron, Jason Hamilton, Mariana Cota, Lida Bubuteishvili Pacaud, Edmund K. Waller. Considerations for Tisagenlecleucel dosing rationale. Poster session presented at: EHA 2018 The 23rd European Hematology Association Congress; 2018 Jun 14-17; Stockholm, Sweden.