Imatinib trough levels: a potential biomarker to predict cytogenetic and molecular response in newly diagnosed patients with chronic myeloid leukemia

Abstract

Therapeutic drug monitoring of imatinib in patients with chronic myeloid leukemia (CML) is an ongoing debate. We studied the influence of imatinib trough levels on therapeutic response in 206 newly diagnosed patients with CML. We also compared the drug levels in patients taking branded and generic imatinib. Imatinib levels were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Marked inter-individual variability was seen in imatinib levels (coefficient of variation = 69%). Trough levels were significantly higher in patients who attained complete cytogenetic response than those who did not (2213.9 ± 1101 vs. 1648.6 ± 1403.4ng/mL; p < .001). Patients with major molecular response (MMR) had higher trough levels than those without MMR (2333.4 ± 1112 vs. 1643.4 ± 1383.9ng/mL; p = .001). Patients with trough levels ≤1000ng/mL were at high risk for failure of imatinib therapy [RR =1.926; 95%CI (1.562, 2.374); p < .001]. Trough levels emerged as an independent predictor of imatinib response in multivariate analysis. To conclude, imatinib trough levels significantly influence cytogenetic and molecular response and might emerge as a potential biomarker for therapeutic response in CML.

Keywords:

• Therapeutic drug monitoring
• imatinib resistance
• pharmacokinetics
• imatinib mesylate
• drug levels
• treatment response
• concentration–response relationship
• tyrosine kinase inhibitor
• chronic myeloid leukemia

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1485907.