Imatinib Plasma Levels and Its Correlation with Response in Chronic-Phase Chronic Myeloid Leukemia: Experience of One Centre.

Abstract

Abstract 4284 IntroductionImatinib (IM), 400 mg/d. induces durable responses in chronic myeloid leukaemia (CML) in chronic phase (CP). However, although IM-biodisponibility is fairly good, its plasma levels are variable and can not be predicted. Recently, these plasma concentrations have been related both to the dose being administrated and to the cytogenetic and molecular responses. Thus, Imatinib pharmacokinetics could be an issue towards treatment optimisation in CML patients. Recent studies suggest that therapeutic IM plasma levels should be above 1040 ng/dl. AimsTo evaluate the association between IM dose and throughout plasma levels with different clinical outcomes. ResultsIn this study, we looked for an association between plasma concentrations and clinical outcomes in 16/86 CML chronic phase patients who did not achieve optimal responses following the European Leukemia Net guidelines (ELN) (table 1). Patients with optimal responses and treated with the same standard doses were also analysed as a control group. Patients receiving doses above 400 mg showed throughout plasma levels considered as appropriate. In 7 of 16 patients (47.5%) not achieving optimal responses (ELN criteria), plasma levels were below the supposed therapeutic ranges. We have found no evidence for a correlation between clinical risk factors at diagnosis and the measurement of optimal plasma levels. ConclusionsIM plasma levels are well correlated with IM dose administrated in the patients studied. In almost 50% of patients who did not achieve optimal responses, IM plasma levels were under the ranges considered therapeutic. Probably these are the patients who may benefit of a dose increase. Obviously, to learn more about the practical value of these measurements a longer follow up with a larger number of patients is needed.IMATINIB RESPONSEIMATINIB DOSESIMATINIB PLASMA LEVELS (ng/dl)MUTATIONS1SUBOPTIMAL400733NO2SUBOPTIMAL8001600NO3SUBOPTIMAL4003490NO4SUBOPTIMAL400853YES5SUBOPTIMAL4002142NO6SUBOPTIMAL400899NO7SUBOPTIMAL4002328NO8SUBOPTIMAL400661NO9SUBOPTIMAL400282NO10SUBOPTIMAL4002208NO11SUBOPTIMAL6001090NO12SUBOPTIMAL4002967NO13SUBOPTIMAL4004221NO14SUBOPTIMAL6001030NO15SUBOPTIMAL4002321NO16SUBOPTIMAL4001469NO Disclosures:No relevant conflicts of interest to declare.