Galimberti Sara, Bucelli Cristina, Arrigoni Elena, Baratè Claudia, Grassi Susanna, Ricci Federica, Guerrini Francesca, Ciabatti Elena, Fava Carmen, D'Avolio Antonio, Fontanelli Giulia, Cambrin Giovanna Rege, Isidori Alessandro, Loscocco Federica, Caocci Giovanni, Greco Marianna, Bocchia Monica, Aprile Lara, Gozzini Antonella, Scappini Barbara, Cattaneo Daniele, Scortechini Anna Rita, La Nasa Giorgio, Bosi Alberto, Leoni Pietro, Danesi Romano, Saglio Giuseppe, Visani Giuseppe, Cortelezzi Agostino, Petrini Mario, Iurlo Alessandra, Di Paolo Antonello
Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy.
Oncohematology Division, IRCCS Ca' Granda, Maggiore Policlinico Hospital Foundation, University of Milan, Milano, Italy.
Oncotarget. 2017 Sep 30;8(50):88021-88033. doi: 10.18632/oncotarget.21406. eCollection 2017 Oct 20.
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.
在慢性髓性白血病中，一线使用尼罗替尼比伊马替尼更有效地实现早期和深度分子反应，尽管三分之一的患者耐受性差或出现治疗失败。酪氨酸激酶抑制剂的毒性和疗效可能取决于跨膜转运蛋白的活性。然而，转运蛋白基因多态性在尼罗替尼治疗中的影响仍存在争议。我们在78例慢性髓性白血病患者的队列中，研究了ABCB1基因单核苷酸多态性（rs683369 [c.480C>G]）以及ABCC2基因单核苷酸多态性（rs1128503 [c.1236C>T]、rs2032582 [c.2677G>T/A]、rs1045642 [c.3435C>T]）与尼罗替尼疗效和毒性之间的可能相关性，研究处于当前临床实践背景下。81%的患者实现了早期分子反应，其中64%的患者达到了深度分子反应（中位时间为26个月）。36个月的无事件生存率为86%，而58%的患者出现了毒性反应。有趣的是，ABCB1和ABCC2基因多态性单独或联合起来均未影响无事件生存率或不良事件发生率。因此，与伊马替尼治疗患者所获得的数据不同，ABCB1和ABCC2基因多态性不会影响尼罗替尼的疗效或毒性。这在一线治疗的选择中可能具有重要意义：那些基因多态性对伊马替尼疗效产生负面影响的患者因此可能接受尼罗替尼作为一线治疗。
