Purpose. The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia. Methods. 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. Results. 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 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. Conclusions. 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.

Association of the hOCT1/ABCB1 genotype with efficacy and tolerability of imatinib in patients affected by chronic myeloid leukemia

LAURINO, MARCO;POLILLO, MARIALUISA;DI PAOLO, ANTONELLO;GUERRINI, FRANCESCA;CIABATTI, ELENA;GRASSI, SUSANNA;DANESI, ROMANO;PETRINI, MARIO;CORNOLTI, FULVIO;GALIMBERTI, SARA
2017

Abstract

Purpose. The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia. Methods. 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. Results. 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 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. Conclusions. 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.
Galeotti, Laura; Ceccherini, Francesco; Domingo, Dario; Laurino, Marco; Polillo, Marialuisa; DI PAOLO, Antonello; Baratè, Claudia; Fava, Carmen; D'Avolio, Antonio; Cervetti, Giulia; Guerrini, Francesca; Fontanelli, Giulia; Ciabatti, Elena; Grassi, Susanna; Arrigoni, Elena; Danesi, Romano; Petrini, Mario; Cornolti, Fulvio; Saglio, Giuseppe; Galimberti, Sara
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/851348
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