Pharmacokinetic/Pharmacodynamic Evaluation of Ivosidenib or Enasidenib Combined With Intensive Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed IDH1/2-Mutant Acute Myeloid Leukemia.

ABSTRACT: Mutant isocitrate dehydrogenase 1/2 (mIDH1/2) proteins catalyze production of the oncometabolite D-2-hydroxyglutarate (2-HG). Ivosidenib and enasidenib are oral inhibitors of mIDH1 and mIDH2, respectively. An open-label phase 1 study is evaluating the safety and efficacy of ivosidenib or enasidenib combined with intensive induction and consolidation chemotherapy in adult patients with newly diagnosed mIDH1/2 acute myeloid leukemia (AML; NCT02632708). In this population, we characterized the pharmacokinetics (PK), pharmacodynamics (PD), and PK/PD relationships for ivosidenib and enasidenib. Patients received continuous oral ivosidenib 500 mg once daily or enasidenib 100 mg once daily combined with chemotherapy. Serial blood samples were collected for measurement of the concentrations of the

SUBMITTER: Fan B 

PROVIDER: S-EPMC9303875 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature