Correlation between imatinib pharmacokinetics and clinical response in japanese patients with chronic-phase chronic myeloid leukemia

N. Takahashi, H. Wakita, M. Miura, S. A. Scott, K. Nishii, M. Masuko, M. Sakai, Y. Maeda, K. Ishige, M. Kashimura, K. Fujikawa, M. Fukazawa, T. Katayama, F. Monma, M. Narita, F. Urase, T. Furukawa, Y. Miyazaki, N. Katayama, K. Sawada

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Abstract

Despite the outstanding results generally obtained with imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), some patients show a poor molecular response. To evaluate the relationship between steady-state trough plasma IM concentration (IM-Cmin) and clinical response in CML patients, we integrated data from six independent Japanese studies. Among 254 CML patients, the mean IM-Cmin was 1,010.5ng/ml. Importantly, IM-Cmin was significantly higher in patients who achieved a major molecular response (MMR) than in those who did not (P = 0.002). Multivariate analysis showed that an MMR was associated with both age (odds ratio (O=R) = 0.97 (0.958-0.995); P = 0.0153) and with IM-Cmin (OR = 1.0008 (1.0003-1.0015); P = 0.0044). Given that patients with IM-Cmin values 1,002ng/ml had a higher probability of achieving an MMR in our large cohort (P = 0.0120), the data suggest that monitoring of IM levels in plasma may improve the efficacy of IM therapy for CML patients.

Original languageEnglish
Pages (from-to)809-813
Number of pages5
JournalClinical Pharmacology and Therapeutics
Volume88
Issue number6
DOIs
StatePublished - Dec 2010

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