Abstract
Purpose
This study aimed to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of ivosidenib in Chinese patients with relapsed or refractory acute myeloid leukemia (R/R AML) carrying the mIDH1 mutation.
Methods
A bridging study (NCT04176393) was conducted involving 29 Chinese patients who received a daily dose of ivosidenib 500 mg in 28-day cycles. Plasma concentrations of ivosidenib and D-2-hydroxyglutarate (2-HG) were measured before and after treatment. Non-compartmental analysis (NCA) was employed to evaluate the PK, and an established population pharmacokinetic (popPK) model developed from non-Chinese patients was externally validated.
Results
The findings revealed comparable PD effects of ivosidenib in Chinese patients with mIDH1 R/R AML. After adjusting for concomitant drug effects, PK characteristics were similar between Chinese and non-Chinese patients. Furthermore, the popPK model offered additional insights into the possible causes of the apparent ethnic difference in PK exposure.
Conclusion
The study indicates that ivosidenib can be used effectively in Chinese patients, and the observed ethnic differences in PK exposure can be explained by concomitant drug effects. The popPK model contributes to a better understanding and optimization of personalized dosing in Chinese patients with mIDH1 R/R AML.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
We would like to thank the patients who participated in this study and their families, as well as the investigators and research staff and their institutions and study coordinators.
Funding
This work was funded by CStone Pharmaceuticals (Suzhou) Co., Ltd.
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Y. S. and A. N. T. contributed to the conception and methodology of the study. Z. Y., C. P., S. W., and Y. S. participated in the study design; Z. Y.: acquisition, analysis, or interpretation of data, drafting of the manuscript. All authors reviewed, revised, and approved of the manuscript.
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Yue, Z., Pan, C., Wang, S. et al. Clinical pharmacokinetics and pharmacodynamics of ivosidenib in Chinese patients with relapsed or refractory IDH1-mutated acute myeloid leukemia. Eur J Clin Pharmacol 80, 105–113 (2024). https://doi.org/10.1007/s00228-023-03591-4
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DOI: https://doi.org/10.1007/s00228-023-03591-4