期刊
CANCER
卷 120, 期 14, 页码 2142-2149出版社
WILEY
DOI: 10.1002/cncr.28705
关键词
FLT3 inhibitors; FLT3-ITD; FLT3-TKD; secondary FLT3 mutations; acute myeloid leukemia
类别
资金
- MD Anderson Cancer Center Support Grant, National Institutes of Health [CA016672]
- AML P01 grant, National Institutes of Health [CA055164 19]
BACKGROUND: FLT3-internal tandem duplication (ITD) mutations are found in approximately 30% of patients with acute myeloid leukemia (AML). FLT3 inhibitors have shown clinical activity in AML with FLT3-ITD, but responses are usually short-lived. METHODS: This study examined 69 FLT3-mutated patients with AML, who were treated with different FLT3 inhibitors to analyze emergence of new mutations. RESULTS: At baseline, 87% of patients had an ITD mutation, 7% had a D835/I836 mutation, and 6% had combined ITD and D835/I836 mutations. Responses occurred in 32% of patients, all with FLT3-ITD; none of the patients with D835/I836 or ITD1D835/I836 responded. Mutational assessment at the time of FLT3 inhibitor discontinuation showed that 68% of patients were unchanged, 10% had become undetectable, and 22% of patients progressed from a single ITD to have combined ITD1D835/I836 mutations. In those patients with unchanged FLT3 mutation at progression, the median survival was 5 months, whereas in those with undetectable and with combined ITD1D835/I836 mutations, the median survival was 7 months, respectively. CONCLUSIONS: These data confirm in vitro observations that a secondary tyrosine kinase domain mutation may arise after the use of FLT3 inhibitors in patients with single FLT3-ITD mutated AML, a phenomenon that is associated with resistance and a poor prognosis. (C) 2014 American Cancer Society.
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