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.

The hOCT1 and ABCB1 polymorphisms do not influence the pharmacodynamics of nilotinib in chronic myeloid leukemia / S. Galimberti, C. Bucelli, E. Arrigoni, C. Baratè, S. Grassi, F. Ricci, F. Guerrini, E. Ciabatti, C. Fava, A. D'Avolio, G. Fontanelli, G. Rege Cambrin, A. Isidori, F. Loscocco, G. Caocci, M. Greco, M. Bocchia, L. Aprile, A. Gozzini, B. Scappini, D. Cattaneo, A.R. Scortechini, G. La Nasa, A. Bosi, P. Leoni, R. Danesi, G. Saglio, G. Visani, A. Cortelezzi, M. Petrini, A. Iurlo, A. Di Paolo. - In: ONCOTARGET. - ISSN 1949-2553. - 8:50(2017 Oct 20), pp. 88021-88033. [10.18632/oncotarget.21406]

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

C. Bucelli
Secondo
;
D. Cattaneo;A. Cortelezzi;
2017

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.
ABC transporters; ABCB1; early molecular response; HOCT1; Nilotinib; oncology
Settore MED/15 - Malattie del Sangue
20-ott-2017
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/551209
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