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.