Optimizing treatment options for patients with chronic myeloid leukemia

Introduction Patients with chronic myeloid leukemia (CML) are usually treated with imatinib 400 mg/day. Despite excellent therapeutic response to imatinib, 20 - 30 % patients are resistant to this treatment. Several molecular mechanisms leading to imatinib resistance have been proposed (amplification and overexpression of the BCR/ABL1 gene, point mutations). It has been suggested that one of the reasons for the varied response to imatinib may be due to inter- individual differences in imatinib metabolism. Objective The primary goal was to find new biological parameters which could clarify the cases of unexplained imatinib failure. In our study we analyzed the influence of polymorphism in seven genes linked to the pharmakokinetics of imatinib: CYP3A5*3 (rs 776746), CYP3A4*1 (rs 2740574), CYP2C9*3 (rs 1057910), SLCO1 (rs 683369), ABCB1 (rs1045642, rs 1128503), ABCG2 (rs 2231142) and ABCC2 (rs 717620). We evaluated the association of these polymorphisms in optimal response and plasma levels of imatinib. The secondary objective was to evaluate whether the standard dose of imatinib 400 mg/daily leads to achieving optimal therapeutic response and whether this dose induces a sufficient plasma levels of imatinib. Methods and results We analyzed 112 patients with CML. Our cohort included 53 men (47 %) and 59..