ARUP now offers a therapeutic drug monitoring (TDM) test for chronic myelogenous leukemia (CML) and gastrointestinal stromal tumor (GIST) patients being treated with the tyrosine kinase inhibitor (TKI) imatinib. Imatinib is a first-line treatment for CML and GIST.
Why Is This Testing Important?
Imatinib, when dosed according to TDM, yields similar major molecular response (MMR) as second generation TKIs.1
TDM Can Improve Dose Optimization
Figure 1. In a study of 1,910 CML samples, imatinib trough plasma concentration levels are shown according to total daily dose. At each dose, mean concentrations are stated and indicated by a horizontal line. The top and bottom of each box represent the 25th and 75th percentiles, and vertical lines indicate the standard deviation. The dotted line corresponds to the imatinib Cmin threshold (1002 ng/mL).2
Imatinib Ordering Information
To standardize lab test ordering in your clinical practice, Imatinib testing can be ordered through your existing laboratory provider. Please reference ARUP test code 3000539.For more information, please contact the clinical product managers.
- Evaluation of an Automated Immunoassay for Quantification of Imatinib in Plasma (Presented at ASH 2017)
- Putting the Precision in Medicine: Imatinib Putting the Precision in Medicine: Imatinib First in a Series of Cancer-Drug TDM ARUP Plans(blog)
- AACC 2018 Booth Presentation: Benefits of Monitoring Plasma Imatinib Concentrations
Imatinib TDM helps you meet goals of improving population health, patient treatment, and reducing the cost of treating of CML and GIST. With the introduction of generic imatinib for the treatment of CML the price is expected to drop.3
A payor perspective analysis over 5 years demonstrated the potential of IM TDM to save hundreds of thousands of dollars.
Clinical Trials Support the Use of TDM For Imatinib Treatment of CML
OPTIM Imatinib Study1 (133 CML Patients)
- Two-thirds (2/3) of patients did not have optimal imatinib exposure and would benefit from individualized TDM
- Major molecular response (MMR) at 12 months was achieved in 63% of patients in arm 1 dosed by TDM, compared to 37% of patients in arm 2 (no TDM; p=0.031)
TOPS Imatinib Trial4 (476 CML patients)
- Imatinib trough levels >1165 ng/mL were associated with a faster time to MMR (p=0.0304)
- Trough levels above 3180 ng/mL were associated with a higher frequency of all grade neutropenia, anemia, and leukopenia. but not thrombocytopenia
Efficacy in CML
1 Rousselot P, et al. Personalized daily doses of imatinib by therapeutic drug monitoring increase the rates of molecular responses in patients with chronic myeloid leukemia. Final results of the randomized OPTIM imatinib study. Blood 2015;126(23):133.
2 Bouchet S, et al. Therapeutic drug monitoring of imatinib in chronic myeloid leukemia: experience from 1216 patients at a centralized laboratory. Fundam Clin Pharmacol 2013;27(6):690–7.
4 Guilhot F, et al. Plasma exposure of imatinib and its correlation with clinical response in the tyrosine kinase inhibitor optimization and selectivity trial. Haematologica2012;97(5):731–8.
Picard S, et al. Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2007;109:3496–99
Efficacy in GIST
Demetri GD, et al. Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J Clin Oncol 2009;27(19): 3141–7.
Health Economic Model - CML
3 Padula WV, et al. Cost-effectiveness of tyrosine kinase inhibitor treatment strategies for chronic myeloid leukemia in chronic phase after generic entry of imatinib in the United States. J Natl Cancer Inst 2016;108(7).
Verheijen RB, et al. Practical recommendations for therapeutic drug monitoring of kinase inhibitors in oncology. Clin Pharmacol Ther2017;102(5):765–76.
Yu H, et al. Practical guidelines for therapeutic drug monitoring of anticancer tyrosine kinase inhibitors: focus on the pharmacokinetic targets.Clin Pharmacokinet 2014;53(4):305–25.
CML and imatinib
Bower H, et al. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol 2016;34(24):2851–7.
Adherence to imatinib
Marin D, et al. Adherence Is the Critical Factor for Achieving Molecular Responses in Patients With Chronic Myeloid Leukemia Who Achieve Complete Cytogenetic Responses on Imatinib J Clin Oncol. 2010 May 10;28(14):2381-8
Pharmacogenetics of imatinib in GIST
Corless CL, et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 2005;23(23):5357–64.
Patrikidou A, et al. Long-term outcome of molecular subgroups of GIST patients treated with standard-dose imatinib in the BFR14 trial of the French Sarcoma Group. Eur J Cancer 2016;52:173–80.