Clinical pharmacokinetics and pharmacodynamics of ivosidenib in Chinese patients with relapsed or refractory IDH1-mutated acute myeloid leukemia

PurposeThis 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.MethodsA 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.ResultsThe 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.ConclusionThe 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.

Automated summary

This study aimed to evaluate the pharmacokinetics and pharmacodynamics of ivosidenib in Chinese patients with relapsed or refractory acute myeloid leukemia carrying the mIDH1 mutation. The results showed comparable pharmacodynamics effects of ivosidenib in Chinese patients with mIDH1 R/R AML. After adjustment for concomitant drug effects, PK characteristics were similar between Chinese and non-Chinese patients. The population pharmacokinetic model contributed to a better understanding and optimization of personalized dosing in Chinese patients with mIDH1 R/R AML.