Hepatic adverse events associated with tyrosine kinase inhibitors in patients with chronic myeloid leukemia

Abstract

Objective: To explore the incidence and severity of hepatic adverse events (AEs) and identify factors associated with hepatic AEs in patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with tyrosine kinase inhibitors (TKIs). Methods: Liver biochemistry parameters [including ALT(alanine aminotransferase), AST(aspartate aminotransferase), ALP(alkaline phosphatase), and TBil(total bilirubin)] during the first 6 months on imatinib (Gleevec(®)), dasatinib (Sprycel(®)) or nilotinib (Tasigna(®)) in CML-CP patients were collected and analyzed retrospectively. Results: A total of 436 patients were enrolled in this study, including 271 with imatinib, 58 with dasatinib, and 107 with nilotinib. The incidences of any abnormality of liver injury were 21.8%(59/271), 15.5%(9/58) and 32.7%(35/107) in the imatinib, dasatinib and nilotinib groups, respectively. Most of the hepatic AEs were CTCAE grade 1 or 2 and mild or moderate liver injury except 1.9% of TBil CTCAE grade 3 in the nilotinib group. Multivariate analyses showed nilotinib [OR=2.9(1.3-6.6), P=0.012; OR=4.4(1.2-15.6), P=0.023] and male gender [OR=2.3(1.4-3.9), P=0.002; OR=3.0(1.2-7.6), P=0.018] were significantly associated with moderate liver impairment. Conclusions: TKIs including imatinib, dasatinib and nilotinib were well tolerated with mild to moderate hepatic AEs in CML-CP patients. Nilotinib and male sex were associated with occurrence of liver biochemistry abnormalities and moderate hepatic injury.