Therapeutic Drug Monitoring of Imatinib in Patients of Chronic Myeloid Leukemia – Chronic Phase

Abstract

Introduction: Tyrosine kinase inhibitor is recommended for the initial management of chronic phase chronic myeloid leukemia (CP CML) based on the more favorable balance of toxicity and long‑term disease control.Background: Mean trough plasma Imatinib Mesylate (IM) levels are detected to be significantly higher in patients with a complete cytogenetic response or major molecular response (MMR).Methodology: The primary objective of the study was to correlate the IM drug levels with MMR on two different occasions at least 3 months apart and to study the variation in the plasma trough levels of IM during the treatment with standard dose for at least 12 months.Results: After exclusion, 30 patients of CML‑CP in MMR, on standard dose over a period of 2 years were finally analyzed. The mean IM plasma levels (IPLs) of the first sample for all patients were 1722 ± 566 ng/ml (IPL‑1) with a corresponding mean molecular response (MR) 0.0257 ± 0.0279 breakpoint cluster region‑abelson murine leukemia (BCR‑ABL) IS % (MR‑1). The mean IPLs of the second sample for all patients were 1549 ± 375 ng/ml (IPL‑2) with a corresponding mean MR 0.0143 ± 0.0184 BCR‑ABL IS % (MR‑2). Area under the receiver operating characteristic curve for IPL‑1 was 0.565 and IPL‑2 was 0.639. For IM level at second point of 1800 ng/ml, the specificity for predicting MMR was 81.8% and sensitivity was 31.6%.Conclusion: Monitoring of trough IM plasma concentrations may become the part of standard management of CML patients.

Keywords: Chronic myeloid leukemia; imatinib; major molecular response; therapeutic drug monitoring