Imatinib plasma trough levels in chronic myeloid leukaemia: Results of a multicentre study CSTI571AIL11TGLIVEC

Imatinib has been accepted as frontline treatment for patients with chronic myeloid leukaemia (CML), and patients generally receive doses ranging from 400 to 800mg/day. Previous studies have demonstrated that maintaining imatinib plasma levels (IMPLs) >1000ng/mL leads to improved responses and long-term outcomes. However, IMPLs vary among patients because of factors such as drug-drug interactions, adherence, toxicity and differential levels of expression of cellular efflux/influx proteins. In this study, IMPLs were analysed in 191 patients with CML and were compared with achievement of molecular and cytogenetic responses (CyR). IMPLs were also correlated with renal and hepatic dysfunction. Additionally, self-reported adherence was monitored. The median and mean IMPLs were 994ng/mL and 1070±686ng/mL, respectively, with 96 patients (50%) achieving plasma levels >1000ng/mL. Self-reported patient compliance was 98%. Patients who achieved a complete CyR (CCyR) had significantly higher IMPLs (1078±545ng/mL) than those without CyR (827±323ng/mL, p=0.045). When grouped together, patients who achieved a CCyR or partial CyR had significantly higher IMPLs than patients who achieved a minimal CyR or did not achieve a CyR (1066ng/mL vs 814ng/mL, p=0.002). There was no significant difference observed in the IMPLs between patients who achieved molecular responses (n=177) on treatment (major molecular response, 976±385ng/mL versus complete molecular response, 1138±809ng/mL, p=0.387). Mean IMPLs were similar in patients with or without renal or hepatic impairment. Overall, this study confirmed previous reports that higher IMPLs correlate with clinical responses and demonstrated that imatinib exposure did not differ in patients with or without liver and/or renal dysfunction. The use of IMPL testing and patient diaries may be practical tools for the management of imatinib therapy in patients with CML.