Population cellular kinetics and exposure-CSR analysis of CAR-T cells in Chinese patients with relapsed/refractory B-ALL.

Authors

Yicong Bian, Jinjie Yuan, Chenrong Huang, Kaijie Zhang, Ling Xue, Fan Xia, Liqing Kang, Yan Wang, Hua Zhang, Lei Yu, Depei Wu, Liyan Miao

Published in

Frontiers in pharmacology. Volume 17. Pages 1878984. Epub Oct 09, 2026.

Abstract

CD19-targeting chimeric antigen receptor (CAR)-T cells have demonstrated great efficacy in treating relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL). Despite the high objective response rate of CAR-T cell therapy, high-risk adverse event of cytokine-release syndrome occur unexpectedly.
As living gene-modified cells, CAR-T cells exhibit unique kinetics. This study aimed to explore the relationship between CAR-T therapy-related CRS and the kinetics of CAR-T cells.
In this study, data for 2184 CAR-transgene copies from 131 B-ALL patients treated with IL-6 knockdown CD19-targeting CAR-T cells were included to characterize the cellular kinetics using a nonlinear mixed-effects (NLME) model. The extrinsic and intrinsic factors that may impact the kinetics of CAR-T cells were also evaluated.
The CD4⁺/CD8⁺ ratio of CAR-T cell products was shown to be significantly positively correlated with T_max, suggesting that a higher CD4⁺/CD8⁺ ratio may lead to a delay in reaching the maximum expansion, while other candidate covariates including tumor burden, CAR-T doses and comedication were not significantly associated with the kinetics of CAR-T cells. The estimated values of the cellular kinetic parameters C_max, T_max and Fold_x were 4.696 × 10⁴ copies/μg, 13.0 days, and 127.5, respectively. The estimated AUC_0-28d and AUC_0-90d accounted for only 13.0% and 18.5% of AUC_0-inf, respectively, indicating that there was long-term persistence of memory CAR-T cells in vivo. In addition, the incidence of CRS was investigated to be correlated with the early kinetics of CAR-T cells, and the optimal cutoff values of C_max and AUC_0-28d for severe CRS were 6.951 × 10⁴ copies/μg and 4.962 × 10⁵ copies/μg × days, respectively.

PMID:
42920606
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.

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