Population cellular kinetics and exposure-CSR analysis of CAR-T cells in Chinese patients with relapsed/refractory B-ALL
- 1Department of Pharmacy, The First Affiliated Hospital of Soochow University , ,
- 2Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd , ,
- 3National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University , ,
Abstract
Background: 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.
Objective: 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.
Methods: 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.
Results: 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 × 10 ⁴ 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 × 10 ⁴ copies/μg and 4.962 × 10 ⁵ copies/μg × days, respectively.
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BibTeX
@article{bian2026population,
title = {{Population cellular kinetics and exposure-CSR analysis of CAR-T cells in Chinese patients with relapsed/refractory B-ALL}},
author = {Yicong Bian and Jinjie Yuan and Chenrong Huang and Kaijie Zhang and Ling Xue and Fan Xia and Liqing Kang and Yan Wang and Hua Zhang and Lei Yu and Depei Wu and Liyan Miao},
journal = {Frontiers in pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1878984},
url = {https://europepmc.org/article/PMC/PMC13690635},
note = {CC BY},
}
RIS
TY - JOUR
TI - Population cellular kinetics and exposure-CSR analysis of CAR-T cells in Chinese patients with relapsed/refractory B-ALL
AU - Yicong Bian
AU - Jinjie Yuan
AU - Chenrong Huang
AU - Kaijie Zhang
AU - Ling Xue
AU - Fan Xia
AU - Liqing Kang
AU - Yan Wang
AU - Hua Zhang
AU - Lei Yu
AU - Depei Wu
AU - Liyan Miao
PY - 2026
DA - 2026/10/09
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1878984
UR - https://europepmc.org/article/PMC/PMC13690635
AB - Background: 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. Objective: 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. Methods: 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. Results: 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 × 10 ⁴ 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 × 10 ⁴ copies/μg and 4.962 × 10 ⁵ copies/μg × days, respectively.
SN - 1663-9812
ER -