Association of the hOCT1/ABCB1 genotype with efficacy and tolerability of imatinib in patients affected by chronic myeloid leukemia
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The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia.
Through a procedure based on a sequence of classical statistics methods, we investigated the possible relationships between treatment efficacy/tolerability and combinations of time-independent variables as gender and genetic covariates in the form of single nucleotide polymorphisms (SNPs) or combinations thereof. Moreover, since the drug tolerability has a strong incidence on the discontinuation of the therapy, we investigated whether the time of manifestation of the most frequent toxic effects can be related to time-independent patients’ characteristics or not.
We found that a combination of two polymorphisms, namely hOCT1 c.480C>G (rs683369) and ABCB1 c.3435C>T (rs1045642), seems to play the role of predictor for imatinib in both efficacy and toxicity. Furthermore, the time of manifestation of edema toxicity is found to be associated to a combination of gender and ABCB1 c.3435C>T, whereas the time of manifestation of cramp toxicity appears related to gender.
The novelty of this study is dual: the achievement of results that potentially have a significant clinical interest and the demonstration that the adoption of composed covariates may represent a unique tool to study different aspects of the treatment with imatinib.
KeywordsImatinib hOCT1 ABCB1 Complete cytogenetic response Tolerability Factor analysis of mixed data
We would like to thank all patients who accepted to participate in the TIKlet study. Funds from the Regione Toscana to G.C. and from University of Pisa (PRA grant) to A.D.P. are gratefully acknowledged.
Compliance with ethical standards
Conflict of interest
ADP and SG served as board members for Novartis Pharma SpA. The other Authors declare that they have no conflict of interest. Furthermore, the present study was performed according to the TIKlet protocol that was approved by the Ethics Committees and every patient gave his/her informed consent to the trial participation.
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