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.