FDA Experience on CAR T Cell Pharmacokinetics/Pharmacodynamics and Model‐Based Assessments

Chimeric antigen receptor T cell (CAR T) therapies are genetically modified T cells that are engineered to recognize specific cell surface antigens (e.g., CD19 or B cell maturation antigen (BCMA), expressed on B cells). The objective of this review is to describe FDA experience with assessing the pharmacokinetics (PK), pharmacodynamics (PD) and conducting model-based analyses of FDA-approved CAR T cell products. The seven currently approved CAR T cell products target CD19 or BCMA and have both flat dose and body-weight-based intravenous dosing. The PK (e.g., expansion and persistence) and PD (e.g., B-cell aplasia, cytokine levels, and chemokine levels) data were an integral component of CAR T cell clinical pharmacology assessments. Model-based assessments, including population PK and exposure-response analysis, were conducted to understand PK variability and identify intrinsic/extrinsic factors impacting safety and efficacy outcomes. Continued use of clinical pharmacology tools such as model-based assessment to inform dose selection, dose optimization, and therapeutic individualization is integral to characterizing the effects of CAR T products.