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

Sara Galimberti, Cristina Bucelli, Elena Arrigoni, Claudia Baratè, Susanna Grassi, Federica Ricci, Francesca Guerrini, Elena Ciabatti, Carmen Fava, Antonio D'Avolio, Giulia Fontanelli, Giovanna Rege Cambrin, Alessandro Isidori, Federica Loscocco, Giovanni Caocci, Marianna Greco, Monica Bocchia, Lara Aprile, Antonella Gozzini, Barbara ScappiniDaniele Cattaneo, Anna Rita Scortechini, Giorgio La Nasa, Alberto Bosi, Pietro Leoni, Romano Danesi, Giuseppe Saglio, Giuseppe Visani, Agostino Cortelezzi, Mario Petrini, Alessandra Iurlo, Antonello D. Di Paolo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)88021-88033
Number of pages13
JournalOncotarget
Volume8
Issue number50
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • ABC transporters
  • ABCB1
  • Early molecular response
  • HOCT1
  • Nilotinib

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Galimberti, S., Bucelli, C., Arrigoni, E., Baratè, C., Grassi, S., Ricci, F., Guerrini, F., Ciabatti, E., Fava, C., D'Avolio, A., Fontanelli, G., Cambrin, G. R., Isidori, A., Loscocco, F., Caocci, G., Greco, M., Bocchia, M., Aprile, L., Gozzini, A., ... Di Paolo, A. D. (2017). The hOCT1 and ABCB1 polymorphisms do not influence the pharmacodynamics of nilotinib in chronic myeloid leukemia. Oncotarget, 8(50), 88021-88033. https://doi.org/10.18632/oncotarget.21406