Effects of SLC22A2 808G>T polymorphism and bosutinib concentrations on serum creatinine in patients with chronic myeloid leukemia receiving bosutinib therapy

The purpose of this study was to investigate the effects of SLC22A2 808G>T polymorphism and trough concentrations (C-0) of bosutinib on serum creatinine in 28 patients taking bosutinib. At 1, 3, 6, 12, 24, and 36 months after administration, analysis of bosutinib C-0 and creatinine was performed at the same time of day. Significant correlations were observed between bosutinib C-0 and the change rate of serum creatinine or the estimated glomerular filtration rate (eGFR; r=0.328, P<0.001 and r=-0.315, P<0.001, respectively). These correlations were particularly high in patients having the SLC22A2 808G/G genotype (r=0.345 and r=-0.329, respectively); however, in patients having the 808T allele, there were no significant differences. In multivariate analyses, the SLC22A2 808G/G genotype, patient age, bosutinib C-0 and second-line or later bosutinib were independent factors influencing the change rate of creatinine. Bosutinib elevated serum creatinine through organic cation transporter 2 (OCT2). We observed a 20% increase in serum creatinine with a median bosutinib C-0 of 63.4-73.2 ng/mL. Periodic measurement of serum creatinine after bosutinib therapy is necessary to avoid progression to severe renal dysfunction from simple elevation of creatinine mediated by OCT2 following bosutinib treatment.