Abstract
Background A good pharmacokinetic/pharmacodynamic correlation between imatinib exposure and therapeutic outcome has been reported. However, therapeutic drug monitoring (TDM) of imatinib in patients with Chronic Myeloid Leukemia (CML) is an ongoing debate. We studied the influence of imatinib trough levels on cytogenetic and molecular response in patients with CML. Methods Newly diagnosed patients with chronic-phase CML, started on Imatinib therapy, were enrolled and followed-up prospectively for 24 months. Plasma trough levels of imatinib were measured using LC-MS/MS. Cytogenetic response was assessed by conventional bone-marrow cytogenetics. Molecular response was assessed by qRTPCR using international scale. Multivariate analysis was done to find the influence of various covariates on imatinib response. Results A total of 206 newly diagnosed patients with CML were enrolled in this study. The mean age at diagnosis was 35.2614 years. Marked inter-individual variability was seen in imatinib trough levels (Coefficient of variation= 69%). Mean imatinib trough level was 190161305 ng/mL. Trough levels were significantly higher in patients who attained complete cytogenetic response than those who didn't (2213.961101 vs. 1648.661403.4ng/mL;P<0.001). Patients with major molecular response(MMR) had higher trough levels than those without MMR (2333.461112 vs. 1643.461383.9 ng/mL; P = 0.001). Patients with trough levels <1002 ng/mL were at a high risk for failure of imatinib therapy[RR=1.926;95%CI(1.562,2.374);P <0.001]. Trough levels of imatinib emerged as an independent predict or of cytogenetic [adjusted OR: 10.488; 95%CI(4.136,26.594);P <0.001] and molecular response [adjustedOR:14.407;95%CI (3.414,60.791);P<0.001]in multivariate analysis. No significant correlation of trough levels with imatinib induced hematological toxicity was seen. Conclusions Trough level so fimatinib significantly influence thecy to genetic and molecular response in patients with CML and might emerge as a potential biomarker to predict therapeutic response. TDM is recommended for individualizing the dosage of imatinib, especially in patients with suboptimal response. Legal entity responsible for the study All India Institute of Medical Sciences, New Delhi, India Funding All India Institute of Medical Sciences, NewDelhi, India Disclosure All authors have declared no conflicts of interest.
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