335O - Imatinib trough levels: A potential biomarker to predict cytogenetic and molecular response in newly diagnosed patients with chronic myeloid leukemia

Date 19 December 2016
Event ESMO Asia 2016 Congress
Session Haematological malignancies
Topics Anti-Cancer Agents & Biologic Therapy
Leukaemia
Translational Research
Presenter Harivenkatesh Natarajan
Citation Annals of Oncology (2016) 27 (suppl_9): ix104-ix111. 10.1093/annonc/mdw586
Authors H. Natarajan1, L. Kumar2, S. Bakhshi2, A. Sharma2, T. Velpandian1, A. Gogia2, Y.K. Gupta1
  • 1Clinical Pharmacology, All India Institute of Medical Sciences, 110029 - New Delhi/IN
  • 2Medical Oncology, All India Institute of Medical Sciences, 110029 - New Delhi/IN

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 35.2±14 years. Marked inter-individual variability was seen in imatinib trough levels (Coefficient of variation= 69%). Mean imatinib trough level was 1901±1305 ng/mL. Trough levels were significantly higher in patients who attained complete cytogenetic response than those who didn’t (2213.9±1101 vs. 1648.6±1403.4 ng/mL; P 

Conclusions

Trough levels of imatinib significantly influence the cytogenetic 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.

Clinical trial indentification

Legal entity responsible for the study

All India Institute of Medical Sciences, New Delhi, India

Funding

All India Institute of Medical Sciences, New Delhi, India

Disclosure

All authors have declared no conflicts of interest.