Correlation of plasma trough levels of imatinib with molecular response in patients with chronic myeloid leukemia

Abstract

The present study looked at the correlation between mean trough Imatinib plasma levels and molecular response in 131 CML patients on imatinib. Patients receiving Glivec versus generic Imatinib were also compared. A ROC curve was constructed to estimate a threshold level that correlates with a favourable response. Patients were grouped into Responders (bcr/abl ration by RQ-PCR less than 1) and Non Responders (ration ≥ 1). The mean trough imatinib plasma level in the responders was significantly higher than in the non responders (p = 0.001). The area under ROC curve was 0.733, with best sensitivity (51.85%) and specificity (89.42%) at a plasma threshold of 0.988 g/ml [1.675 M]. Levels in the patients on Glivec versus generic drug (p > 0.05) were comparable. Trough Imatinib plasma levels may be a marker for suboptimal response and may identify patients in whom increase of drug dose or change in therapy may be indicated.

Keywords::

• Chronic myeloid leukemia (CML)
• imatinib
• major molecular response (MMR)
• real time polymerase chain reaction (RQ-PCR)
• receiver operating characteristic (ROC) curve

Acknowledgements

The authors gratefully acknowledge the Indian Council of Medical Research (ICMR), Government of India, for a research fellowship awarded to to Pratibha Sharma (Grant No. 3/2/2/7/2010/NCD-III) and the Indian Cooperative Oncology network (ICON) for a research grant for this project. We thank Dr. Vikram Gotta, Advanced Center for Treatment, Research & Education in Cancer, Mumbai and Dr. Ashok Kumar and the Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur for help in HPLC analysis.

Potential conflict of interest

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