BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase.
BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase.
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DOI：
10.1038/leu.2015.168
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发表时间：
2015-09
期刊：
影响因子：
11.4
通讯作者：
Hochhaus A
中科院分区：
文献类型：
--
作者：
Hughes TP;Saglio G;Quintás-Cardama A;Mauro MJ;Kim DW;Lipton JH;Bradley-Garelik MB;Ukropec J;Hochhaus A
BCR-ABL 1突变是伊马替尼作为慢性期慢性粒细胞白血病（CML-CP）一线治疗的一种常见的、充分表征的耐药机制。尽管与伊马替尼相比，达沙替尼和尼洛替尼的缓解率更高，但对达沙替尼和尼洛替尼一线治疗期间的突变发展知之甚少。在DASISION（达沙替尼与伊马替尼治疗初治CML-CP的研究）中，进行了回顾性分析，以描述接受达沙替尼（n=259）或伊马替尼（n=260）治疗的新诊断CML-CP患者的突变发展特征，至少随访3年。突变筛查，包括停止治疗的患者和发生临床相关治疗期间事件的患者（12个月内无确认的完全细胞遗传学缓解（cCCyR）和无主要分子学缓解（MMR）; BCR-ABL 1增加5倍，MMR丧失; CCyR丧失），产生了少量突变患者（达沙替尼，n=17;伊马替尼，n=18）。达沙替尼患者的突变谱更窄（达沙替尼与伊马替尼相比，有4个位点，12个位点），磷酸结合环突变更少（1个突变与9个突变），多重突变更少（1例患者与6例患者），T315 I的发生率更高（11例患者与0例患者）。本试验在www.clinicaltrials.gov上注册为NCT 00481247。
BCR-ABL1 mutations are a common, well-characterized mechanism of resistance to imatinib as first-line treatment of chronic myeloid leukemia in chronic phase (CML-CP). Less is known about mutation development during first-line treatment with dasatinib and nilotinib, despite increased use because of higher response rates compared with imatinib. Retrospective analyses were conducted to characterize mutation development in patients with newly diagnosed CML-CP treated with dasatinib (n=259) or imatinib (n=260) in DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML-CP), with 3-year minimum follow-up. Mutation screening, including patients who discontinued treatment and patients who had a clinically relevant on-treatment event (no confirmed complete cytogenetic response (cCCyR) and no major molecular response (MMR) within 12 months; fivefold increase in BCR-ABL1 with loss of MMR; loss of CCyR), yielded a small number of patients with mutations (dasatinib, n=17; imatinib, n=18). Dasatinib patients had a narrower spectrum of mutations (4 vs 12 sites for dasatinib vs imatinib), fewer phosphate-binding loop mutations (1 vs 9 mutations), fewer multiple mutations (1 vs 6 patients) and greater occurrence of T315I (11 vs 0 patients). This trial was registered at www.clinicaltrials.gov as NCT00481247.