The clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study

Abstract

This retrospective multicenter study in patients with chronic myeloid leukemia in chronic phase was undertaken to confirm the clinical relevance of imatinib plasma concentrations monitoring in daily practice. Forty-one patients, with 47 imatinib plasma measurements, were analyzed during treatment with imatinib given at a fixed 400 mg daily dose. A significant inverse relationship of imatinib concentration with the patients' weight was observed (Pearson's test: p = 0.02, R 2 = 0.1). More interestingly, patients with poor response (switched to another tyrosine kinase inhibitor because of imatinib failure, or because of disease progression after an initial response) displayed a significantly lower mean imatinib concentration as compared to patients maintained on imatinib (822 ng/mL vs 1099 ng/mL; Student's t-test, p = 0.04). Failure or disease progression occurred more often in patients in the lowest quartile of imatinib concentrations compared to patients in the highest quartile (p = 0.02, logrank test). No correlation could be established with other biological or clinical parameter, including complete cytogenic response and major molecular response. In conclusion: in patients treated with imatinib at a fixed daily dose of 400 mg, imatinib plasma concentrations decreased with increasing body weight and were lower in patients switched to another tyrosine kinase inhibitor due to imatinib failure. Systematic determination of imatinib plasma trough levels should be encouraged in such patients.

Correlations between imatinib plasma trough concentration and adverse reactions in Chinese patients with gastrointestinal stromal tumors

“…Another reason for the higher C min at 600 mg daily in our study may be that we divided the 600 mg daily dose into 300 mg twice daily to minimize gastrointestinal reactions, whereas the B2222 trial used a once daily dose of 600 mg daily. Consistent with previous reports of patients with GIST and chronic myeloid leukemia, age, body weight, plasma albumin level, and creatinine clearance were significant covariates for imatinib plasma exposure; and higher values were correlated with a lower imatinib C min , except for age. However, the overall effect of these covariates on imatinib plasma exposure was small, and there may be other influencing factors, including food intake, major gastric resection, and cytochrome P450 and drug transporter sequence variants …”

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

“…Several other studies have also found that patients with better treatment outcomes also had higher C min values 23, 24…”

Factors Influencing the Steady-State Plasma Concentration of Imatinib Mesylate in Patients With Gastrointestinal Stromal Tumors and Chronic Myeloid Leukemia

“…1) Steady-state plasma concentration patients did not have the same inclusion criteria. Some had been on monotherapy with 400 mg of IM per day for at least 30 days (Adeagbo et al, 2017;Farag et al, 2017;Van Obbergh et al, 2017) and had taken the drug consistently for the last 5 days prior to the time of blood collection; others were on the therapy for at least 90 days (Hompland et al, 2016) or even 120 days (Seong et al, 2013). Whether IM resistance or disease progression will occur with the extension of IM treatment time might be a potential factor to affect the IM trough concentration.…”