engleski

Abstracts from First Nordic conference on personalized medicine 2018 in Nyborg, Denmark

Aims: Treatment of chronic myeloid leukemia (CML) is based on wide range of tyrosine kinase inhibitors (TKIs). The aim of this case report is to describe patient with different tolerability to TKIs that could be explain by pharmacogenetic predisposition. According to literature, imatinib, nilotinib and dasatinib exhibit distinct interaction profiles with ABCB1 and ABCG2 transporters. For bosutinib literature is discordant whether it is substrate of ABCB1 transporter or not. Additionally, imatinib is metabolised by CYP2C9, CYP2D6, CYP3A4/5, while nilotinib, dasatinib and bosutinib by CYP3A4 enzymes. Methods: A 69-year-old woman was prescribed dasatinib 80 mg/day.Patient developed following adverse drug reactions (ADRs) malaise, cough and dyspnoea and subsequently dose was reduced to 40 mg/day. Adverse drug reactions disappeared on lower doses and dose was increased to 60 mg/day and 80 mg/day, every second day but adverse reactions again reoccurred. Dasatinib was stooped and bosutinib was introduced in dose of 100 mg–400 mg/day without ADRs. Results: Pharmacogenetic testing (PGX) revealed low expression of P-gp transporter and intermediate activity of transporter ABCC2 -24C/ T and of enzymes CYP2D6 *1/*4 CYP2C9*1/*3 CYP2C19*1/*2 . Normal activity was observed for CYP3A4 (tested for*22) and ABCG2 (tested for 421C>A). Our results suggest that low activity of P-gp transporter could have contributed to the ADRs of dasatinib but did not cause ADRs of bosutinib. Conclusion: This case suggests possible utility of pharmacogenetic testing to inform prescriber about the TKI with the lowest potential for ADRs for individual patient. Further research should be done to further elucidate pharmacogenetic predisposition for ADRs of certain TKIs.

chronic myeloid leukemia, tyrosine kinase inhibitors, imatinib, nilotinib, dasatinib, pharmacogentic polymorphism, transporters ABCB1, ABCG2

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