Plasma concentrations of venetoclax and Pharmacogenetics correlated with drug efficacy in treatment naive leukemia patients: a retrospective study.

Autor: Li Y; Department of Pharmacy, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.; School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, China., Wan Q; Department of Pharmacy, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China., Wan J; Department of Pharmacy, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.; School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, China., Xiao X; Department of Pharmacy, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China., Hu J; Department of Pharmacy, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.; School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, China., Yang X; Department of Pharmacy, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.; School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, China., Kong F; Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China., Wang J; Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China., Song B; Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China., Li Z; Department of Pharmacy, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China., Li F; Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China., Ren S; National Center for Clinical Laboratories, Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. rensimei4162@bjhmoh.cn., Peng H; Department of Pharmacy, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. wavypeng1985@126.com.; School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, China. wavypeng1985@126.com.
Jazyk: angličtina
Zdroj: The pharmacogenomics journal [Pharmacogenomics J] 2024 Nov 22; Vol. 24 (6), pp. 37. Date of Electronic Publication: 2024 Nov 22.
DOI: 10.1038/s41397-024-00359-6
Abstrakt: Venetoclax (VEN) was the only Bcl-2 inhibitor approved yet and showed large differences in clinical efficacy. The aim of the study was to explore the relationships between the plasma concentration and efficacy of VEN, and identify potential influencing factors. A retrospective cohort study was conducted and a total of 76 trough (C 0h ) and 91 6 h post-dose plasma concentration (C 6h ) blood concentrations of VEN were collected in 54 patients. C 6h /D concentration of VEN was found to be significantly correlated with treatment efficacy (p = 0.006) in leukemia patients with good or intermediate prognosis stratification. A ROC curve was then established and the cut-off value was calculated as 0.2868 μg/ml (AUC = 0.7097, p = 0.1081). Besides, patients co-administered with triazoles or carrying CYP3A5 rs776746 AA/AG genotypes were prone to induce higher VEN plasma concentration regardless of whether VEN dosage was reduced or not. Through LASSO-logistic regression and nomogram analysis, chemotherapy regimens and neutrophil percentages were identified as the critical elements that may predict drug response. Above all, in addition to identify prognostic stratification, AML patients taken with VEN were suggested to test plasma concentration routinely so as to achieve desired efficacy, especially when co-administered with triazoles or carried with CYP3A5 rs776746 AA/AG.
Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods in this study were carried out in accordance with relevant guidelines and regulations. The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University (IIT 2024190), and all ethical standards and requirements were strictly adhered to. All participants involved in this study signed an informed consent form, and ensured that the privacy and personal information of the participants were fully protected throughout the research process.
(© 2024. The Author(s).)
Databáze: MEDLINE
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