OBJECTIVETo investigate the correlation of the serum minimal concentrations (Cmins) of nilotinib(NIL) with the clinical efficacy and adverse events (AEs) in CML patients.

METHODSA total of 54 patients were divided into two groups according to the dosage of nilotinib. 44 cases received dose of 600-800 mg/d were classified as group A; while 10 cases received dose of 400 mg/d as group B. The Cmins of nilotinib were determmined by liquid chromatography-tandem mass spectrometry.

RESULTSMedian Cmins of nilotinib in 54 patients was 1.71 (0.52-5.93) µg/ml. Cmins of nilotinib in group A and group B were 2.09± 1.21 µg/ml and 0.94± 0.27 µg/ml respectively, Cmins of group A was significantly higher than that of group B (P=0.001). In group A, 24 out of 44 cases obtained major molecular response (MMR) in 12 months, while 20 cases did not reach MMR in 12 months; the serum drug concentrations were 1.70± 0.75 µg/ml and 2.03± 0.82 µg/ml respectively, without statistically significant differences between these 2 subgroups(P=0.154). However, Cmins of nilotinib in patients with III-IV grade of adverse events were significantly higher than those in patients with 0-II grade of adverse events (3.09± 1.76 µg/ml vs 1.76± 0.68 µg/ml)(P=0.018). There was no statistic diffence in Cmins of nilotinib with MMR in 12 months of group A MMR 1.15± 0.27 µg/ml vs no MMR 0.83± 0.24 µg/ml(P=0.051). The MMR rate at 12 months in group A was 54.5%(24/44) and that in group B was 40%(4/10) (P=0.494). But the incidence of grade III-IV adverse events in group A was 29.5%(13/44), which was significantly higher than that of group B[0/10(0%)].

CONCLUSIONCmins of nilotinib shows significant individual differences. The Cmins of nilotinib relate with the dosage and grade III-IV of adverse events. The lower dose of nilotinib may maintain a good therapeutic effect and significantly reduce the adverse events.