Comparative pharmacokinetic derivations for axicabtagene ciloleucel and brexucabtagene autoleucel in the treatment of B cell malignancies

Axicabtagene ciloleucel (axi-cel) and brexucabtagene autoleucel (brexu-cel) are autologous anti-CD19 chimeric antigen receptor (CAR) T cell products originally approved in the pivotal ZUMA-1 and ZUMA-2 clinical studies for the treatment of relapsed/refractory (r/r) large B cell lymphoma (r/r LBCL) and r/r mantle cell lymphoma (MCL), respectively. The pharmacokinetics (PKs) of axi-cel and brexu-cel are well characterized to associate with safety and efficacy. Methods for deriving molecular PKs to quantify CD19 CAR T cell levels in clinical trials and real-world settings vary widely, lack standardization, and often do not consistently account for cellular composition. This study evaluated three distinct PK derivation methods for axi-cel and brexu-cel, utilizing either quantitative polymerase chain reaction (qPCR) or droplet digital PCR (ddPCR), with corresponding units: (1) qPCR (CAR T cells/μL of blood), (2) ddPCR standard (CAR copies/μg of DNA), and (3) ddPCR normalized (CAR T cells/μL of blood). This study further examined correlations between PK and clinical outcomes in ZUMA-1 and ZUMA-2. Across the methods, qPCR and ddPCR normalized were more tightly associated, whereas ddPCR standard poorly correlated with qPCR and ddPCR normalized. qPCR and ddPCR normalized strongly correlated with objective responses and toxicity compared to ddPCR standard . The findings provide a framework for axi-cel and brexu-cel PK derivations to facilitate longitudinal CAR T cell monitoring.