IMPACT OF ABCB1 AND ABCG2 POLYMORPHISMS ON TROUGH IMATINIB CONCENTRATION IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Chronic myeloid leukemia (CML) is a myeloproliferative disorder effectively managed with tyrosine kinase inhibitors (TKIs) like imatinib. However, drug resistance and suboptimal responses remain challenges. Polymorphisms in drug transporter genes, such as ABCB1 and ABCG2, can influence imatinib plasma concentrations and treatment outcomes. The primary research question was: "Is there an association between polymorphisms in the ABCB1 and ABCG2 genes and imatinib plasma concentration in patients with chronic myeloid leukemia?" We searched in Medline, Embase, and Web of Science databases for studies that evaluated the association between ABCB1 and ABCG2 polymorphisms and imatinib plasma concentrations in CML patients. Treatment effects were quantified using the mean difference (MD) with associated 95% confidence intervals (CIs). Six studies were included with 654 heterozygous patients, 416 variants, and 470 wild-type. The follow-up ranged from 24 to 83 months. A significant increase in imatinib trough concentration (Ctrough) was observed in patients with the ABCB1 c.3435C>T TT genotype compared to the CC genotype (MD 207.54, 95% CI 101.46-313.62, p = 0.051). Additionally, patients with the ABCB1 c.2677G>T GG genotype exhibited significantly higher Ctrough levels compared to both GT (MD 432.52, 95% CI 241.24-623.79, p = 0.006) and TT genotypes (MD 396.96, 95% CI 190.12-603.79, p < 0.001). For the ABCB1c.1236C>T polymorphism, patients with the TT genotype had significantly lower Ctrough levels compared to TC genotypes (MD -350.50, 95% CI -559.51, -141.50, p = 0.059). No significant association was found between the ABCG2 c.412C>A polymorphism and imatinib Ctrough. Genetic polymorphisms of ABCB1 drug transporter proteins play an important role in the serum concentration of imatinib, since some mutations such as variant c.3435C, wild type c.2677G and variant c.1236C showed significant increase Ctrough level when compared to other variants. Mutations of the ABCG2 transporter did not show statistically significant differences. Further studies could be performed to evaluate the impact of implementation of genetic testing on clinical practice.