Effects of Trough Concentration and Solute Carrier Polymorphisms on Imatinib Efficacy in Chinese Patients with Chronic Myeloid Leukemia

Abstract

Purpose: We investigated the relationship between imatinib trough concentrations and genetic polymorphisms with efficacy of imatinib in Chinese patients with chronic myeloid leukemia (CML). Methods: There were 171 eligible patients. Peripheral blood samples were collected from 171 eligible patients between 21 and 27 hours after the last imatinib administration. Complete cytogenetic response (CCyR), major molecular response (MMR) and complete molecular response (CMR) were used as metrics for efficacy. Nine single nucleotide polymorphisms in 5 genes, SLC22A4 (917 T>C, -248 C>G and -538 C>G), SLC22A5 (-945 T>G and -1889 T>C), SLCO1A2 (-361 G>A), SLCO1B3 (334 T>G and 699 G>A) and ABCG2 (421C>A) were selected for genotyping. Results: Patients with CCyR achieve higher trough concentrations than those without CCyR (1478.18±659.83 vs 984.89±454.06 ng mL^-1, p<0.001). Patients with MMR and CMR achieve higher trough concentrations than those without MMR and CMR, respectively (1486.40±703.38 vs 1121.17±527.14 ng mL^-1, p=0.007; 1528.00±709.98 vs 1112.67±518.35 ng mL^-1, p=0.003, respectively). Carriers of A allele in SLCO1A2 -361G>A achieve higher CCyR and MMR rates (p=0.047, OR=4.320, 95% CI: 0.924-20.206; p=0.042, OR=2.825, 95% CI: 1.016-7.853, respectively). Both trough concentrations and SLCO1A2 -361G>A genotypes are independent factors affecting imatinib efficacy. The positive and negative predictive values for CCyR are 71.01% and 68.75%, respectively. The positive and negative predictive values for MMR are 62.86% and 69.70%, respectively. Conclusion: Imatinib trough concentrations and SLCO1A2 -361G>A genotypes are associated with imatinib efficacy in Chinese patients with CML. Keywords: Efficacy, Imatinib, Polymorphisms, Trough concentration