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

This retrospective multicenter study in patients with chronic myeloid leukemia in chronic phase was undertaken to confirm the clinical relevance of imatinibplasma concentrations monitoring in daily practice. Forty-one patients, with 47 imatinibplasma measurements, were analyzed during treatment with imatinibgiven at a fixed 400 mg daily dose. A significant inverse relationship of imatinibconcentration with the patients' weight was observed (Pearson's test: p = 0.02, R2 = 0.1). More interestingly, patients with poor response (switched to another tyrosine kinase inhibitorbecause of imatinibfailure, or because of disease progression after an initial response) displayed a significantly lower mean imatinibconcentration 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 quartileof imatinibconcentrations 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 imatinibat a fixed daily dose of 400 mg, imatinibplasma concentrations decreased with increasing body weight and were lower in patients switched to another tyrosine kinase inhibitordue to imatinibfailure. Systematic determination of imatinibplasma trough levelsshould be encouraged in such patients.