Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis
Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis
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DOI：
10.1182/blood-2006-09-046888
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发表时间：
2007-04-15
期刊：
影响因子：
20.3
通讯作者：
Baccarani, Michele
中科院分区：
文献类型：
--
作者：
Cortes, Jorge;Rousselot, Philippe;Baccarani, Michele
慢性粒细胞白血病（CML）患者的髓系原始细胞危象（MBC）或淋巴样原始细胞危象（LBC）的预后仍然很差。尽管伊马替尼可以在这些患者的一个子集中诱导反应，但对药物的耐药性迅速发展。达沙替尼是一种新型、口服、多靶点的BCR-ABL和SRC家族激酶抑制剂。在获得了有希望的1期结果后，我们报告了达沙替尼在伊马替尼耐药或不耐受急变CML患者中的2期临床试验结果（MBC，n = 74; LBC，n = 42）。在8个月随访时，达沙替尼分别在34%和31%的MBC和LBC-CML患者中诱导了主要血液学缓解（MaHR），在31%和50%的这些患者中诱导了主要细胞遗传学缓解（MCyR）。这些MCyR中的大多数（86%）为完全细胞遗传学缓解（CCyR）。缓解迅速且持久：分别有88%和46%的MBC-和LBC-CML患者在8个月随访时未发生疾病进展。有和无已知对伊马替尼耐药的BCR-ABL突变的患者的缓解率相似。达沙替尼耐受性良好。非血液学不良事件为轻度至中度。血细胞减少症很常见，可通过剂量调整进行管理。达沙替尼具有高度活性，在大量伊马替尼耐药或不耐受MBC和LBC-CML患者中产生血液学和细胞遗传学应答。这些试验在www.clinicaltrials.gov上注册为#CA180006和#CA180015。
The prognosis for patients with chronic myelold leukemia (CML) in myeloid blast crisis (MBC) or lymphoid blast crisis (LBC) remains poor. Although imatinib can induce responses in a subset of these patients, resistance to the drug develops rapidly. Dasatinib is a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases. After promising phase 1 results, we report the results of phase 2 clinical trials of dasatinib in patients with imatinib-resistant or -intolerant blast crisis CML (MBC, n = 74; LBC, n = 42). At the 8-month follow-up, dasatinib induced major hematologic responses (MaHRs) in 34% and 31% of MBC- and LBC-CML patients and major cytogenetic responses (MCyRs) in 31% and 50% of these patients, respectively. Most (86%) of these MCyRs were complete cytogenetic responses (CCyRs). Responses were rapid and durable: 88% and 46%, respectively, of MBC- and LBC-CML patients achieving MaHR had not experienced disease progression at the 8-month follow-up. Response rates were similar in patients with and without BCR-ABL mutations known to confer resistance to imatinib. Dasatinib was well tolerated. Nonhematologic adverse events were mild to moderate. Cytopenias were common and could be managed by dose modification. Dasatinib is highly active and produces hematologic and cytogenetic responses in a significant number of patients with imatinib-resistant or -intolerant MBC- and LBC-CML. These trials were registered at www.clinicaltrials.gov as #CA180006 and #CA180015.