The and polymorphisms do not influence the pharmacodynamics of nilotinib in chronic myeloid leukemia.

Oncotarget 2017 Oct 30;8(50):88021-88033. Epub 2017 Sep 30.

Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Pisa, Pisa, Italy.

First-line nilotinib in chronic myeloid leukemia is more effective than imatinib to achieve early and deep molecular responses, despite poor tolerability or failure observed in one-third of patients. The toxicity and efficacy of tyrosine kinase inhibitors might depend on the activity of transmembrane transporters. However, the impact of transporters genes polymorphisms in nilotinib setting is still debated. We investigated the possible correlation between single nucleotide polymorphisms of (rs683369 [c.480C>G]) and (rs1128503 [c.1236C>T], rs2032582 [c.2677G>T/A], rs1045642 [c.3435C>T]) and nilotinib efficacy and toxicity in a cohort of 78 patients affected by chronic myeloid leukemia in the context of current clinical practice. The early molecular response was achieved by 81% of patients while 64% of them attained deep molecular response (median time, 26 months). The 36-month event-free survival was 86%, whereas 58% of patients experienced toxicities. Interestingly, and polymorphisms alone or in combination did not influence event-free survival or the adverse events rate. Therefore, n contrast to data obtained in patients treated with imatinib, and polymorphisms do not impact on nilotinib efficacy or toxicity. This could be relevant in the choice of the first-line therapy: patients with polymorphisms that negatively condition imatinib efficacy might thus receive nilotinib as first-line therapy.

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Source
http://dx.doi.org/10.18632/oncotarget.21406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675690PMC
October 2017
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