Niveau de preuve du suivi thérapeutique pharmacologique des inhibiteurs de tyrosine-kinase dans le traitement des leucémies myéloïdes chroniques

Abstract

During the last decade, imatinib was current gold standard treatment of chronic myelogenous leukemia (CML), showing a great effectiveness. Thus, the Therapeutic Drug Monitoring (TDM), rarely applied in clinical oncology practice, did not appear necessary at the moment. However, the absence of response among patients and the metabolic profile of imatinib (involving the CYP3A4) suggested the existence of a great interindividual variability. During the last 4 years, studies about the pharmacokinetic/pharmacodynamic relationship have confirmed this variability and highlighted a relation between the trough concentrations of imatinib and the clinical response. An effectiveness threshold, close to 1000 ng/mL, seems to be correlated with better cytogenetic and molecular responses. Consequently, TDM could assist in investigation of the observance, the absence of response, the drug-drug interactions, but the proof of its utility requires complementary studies. In conclusion, the level of proof of imatinib TDM in LMC varies between levels "recommended" and "potentially useful".

Keywords: imatinib; inhibiteur de tyrosine-kinase; level of evidence; niveau de prevue; pharmacokinetic/pharmacodynamic relationship; relation pharmacocinétique/pharmacodynamie; suivi thérapeutique pharmacologique; therapeutic drug monitoring; tyrosine-kinase inhibitor.