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Oncotarget. 2017 Sep 30;8(50):88021-88033. doi: 10.18632/oncotarget.21406. eCollection 2017 Oct 20.

The hOCT1 and ABCB1 polymorphisms do not influence the pharmacodynamics of nilotinib in chronic myeloid leukemia.

Author information

1
Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy.
2
Oncohematology Division, IRCCS Ca' Granda, Maggiore Policlinico Hospital Foundation, University of Milan, Milano, Italy.
3
Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Pisa, Pisa, Italy.
4
GeNOMEC, University of Siena, Siena, Italy.
5
Hematology Division, Ospedale Mauriziano, Torino, Italy.
6
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Torino, Torino, Italy.
7
Department of Clinical and Biological Sciences, University of Torino, AOU San Luigi Gonzaga, Torino, Italy.
8
Hematology and Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy.
9
Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
10
Division of Hematology, Ospedale Le Scotte, University of Siena, Siena, Italy.
11
Division of Hematology, AOU Careggi, University of Florence, Firenze, Italy.
12
Division of Hematology, Marche Polytechnic University, Ancona, Italy.

Abstract

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 hOCT1 (rs683369 [c.480C>G]) and ABCB1 (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, hOCT1 and ABCB1 polymorphisms alone or in combination did not influence event-free survival or the adverse events rate. Therefore, in contrast to data obtained in patients treated with imatinib, hOCT1 and ABCB1 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.

KEYWORDS:

ABC transporters; ABCB1; early molecular response; hOCT1; nilotinib

Conflict of interest statement

CONFLICTS OF INTEREST SG, ADP, AI, GS, GRC, MP, CF participated to advisory boards sponsored by Novartis. Nevertheless, all authors declare no conflicts of interest concern this spontaneous, not industry-sponsored study.

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