Do genetic polymorphisms influence imatinib trough concentrations in patients with chronic myeloid leukemia? A systematic review and meta-analysis.

INTRODUCTION

Chronic myeloid leukemia (CML) is effectively treated with tyrosine kinase inhibitors such as imatinib, though drug response varies among patients. Genetic polymorphisms in drug transporter genes ABCB1 and ABCG2 influence imatinib plasma trough concentrations (Ctrough).

METHODS

Statistical analyses were performed using fixed-effect models and heterogeneity was assessed using I² statistic.

RESULTS

This meta-analysis evaluated nine studies including 1,098 heterozygous patients, 519 variant carriers, and 896 wild-type individuals. Results showed significantly higher Ctrough in patients with the ABCB1 c.3435C>T TT genotype compared with CC with data of 7 studies (MD = 299.84; 95% CI: 208.06-391.62; P = 0.0097; I² = 77%). Similarly, ABCB1 c.2677G>T GT (MD = 327.62; 95% CI: 198.90-456.34; P = 0.0008; I² = 52%) and TT (MD = 289.22; 95% CI: 135.63-442.81; P < 0.001; I² = 12%) genotypes were associated with higher levels than GG, both assessed by 4 studies. Additionally, data from 5 studies observed that ABCG2 c.412C>A CA carriers had increased Ctrough versus CC (MD = 186.83; 95% CI: 67.11-306.56; P = 0.022; I² = 32%).

CONCLUSIONS

These findings support the role of pharmacogenetic screening in optimizing imatinib therapy, improving efficacy, and reducing risks of adverse outcomes.

REGISTRATION: PROSPERO (CRD42024574179).