Management of chronic myelogenous leukemia using therapeutic drug monitoring of imatinib: the French experience of a centralized laboratory

7087 Background: The current gold standard treatment of chronic myelogenous leukemia (CML) is imatinib, a tyrosine kinase inhibitor. We have previously shown the necessity to obtain a trough plasma threshold of 1000 ng/mL for efficient treatment of imatinib. We now routinely perform centralized quantification for patients in France. This has allowed the assessment of imatinib therapeutic monitoring and its use in a real life setting. Methods: A database was created from CML patients containing cytogenetic and molecular statuses, the reason of request (monitoring, insufficient response, non-compliance), dose of imatinib and the associated treatments, as well as possible adverse events. Results: After one year of data collection, we had gathered more than 1000 samples for almost 700 patients (mean age 55 years, F/M sex ratio 0.67) treated by imatinib 400 mg (median) range(100–800mg). For these, the mean concentration was 1020 ng/mL (median: 825 ng/mL) with 60% of low concentrations (< 1000 ng/mL). Plasma concentration increased with dose, although inter-individual variability was large and intra- individual variability was smaller. For plasma concentrations 1000 ng/mL this was 510 mg. For 124 patients having had more than 2 samples, only 28% had initial concentration < 1000 ng/mL (mean concentration of 1st sample: 581 ng/mL. Among the 31 patients who initially had a plasma concentration below 1000 ng/mL that subsequently rose above this threshold, about 50% had their imatinib dose increased; the rest did not have a dose modification. In cases where there was suspicion of a drug-drug interaction, the most frequently combined drugs were proton pump inhibitors, diuretics, allopurinol. The most recurrent adverse effects were digestive, hematological and muscular cramps. Conclusions: Although the studied population had same characteristics generally described for this pathology, there was probably selection bias at the beginning of study: we received first and foremost the patients having an insufficient response, and therefore low plasma concentration. Therapeutic drug monitoring of imatinib appears to be helpful for the management of CML. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis