Compassionate use of sorafenib in FLT3-ITD-positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation

被引:201
作者
Metzelder, Stephan [1 ]
Wang, Ying [1 ]
Wollmer, Ellen [1 ]
Wanzel, Michael [2 ]
Teichler, Sabine [1 ]
Chaturvedi, Anuhar [1 ]
Eilers, Martin [3 ]
Enghofer, Erich [4 ]
Neubauer, Andreas [1 ]
Burchert, Andreas [1 ]
机构
[1] Univ Marburg, Med Ctr Univ Giessen & Marburg, Dept Hematol Oncol & Immunol, Marburg, Germany
[2] Inst Mol Biol & Tumor Res, Marburg, Germany
[3] Univ Wurzburg, Dept Physiol Chem, Bioctr, Wurzburg, Germany
[4] Bayer Schering Pharma, BU Oncol, Leverkusen, Germany
关键词
INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; FLT3; GENE; MYELODYSPLASTIC SYNDROME; RISK GROUP; CHEMOTHERAPY; MUTATIONS; PROGNOSIS; IMATINIB; TRIALS;
D O I
10.1182/blood-2009-03-208298
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Acute myeloid leukemia (AML) patients with internal tandem duplication (ITD) mutations in the Fms-like tyrosine-3 (FLT3) gene have a dismal prognosis. Here we report compassionate-use results with the multikinase and FLT3-ITD inhibitor sorafenib for the treatment of relapsed or refractory FLT3-ITD-positive AML. Sorafenib induced clinically meaningful and very rapid responses in all 6 patients treated either before (n = 2), after (n = 3), or both before and after (n = 1) allogeneic stem cell transplantation (allo-SCT). Sorafenib-induced remissions facilitated allo-SCT in 2 of the 3 refractory patients. Two of the 4 patients who were treated after allo-SCT survived 216 and 221 days, respectively, whereas the other 2 remain in ongoing complete molecular remission. Sorafenib response was associated with an inhibition of the antiapoptotic FLT3-ITD target Stat-5 in vivo. Together, sorafenib monotherapy before or after allo-SCT has remarkable clinical activity in poor risk FLT3-ITD-positive AML and deserves further evaluation in prospective clinical trials. (Blood. 2009; 113: 6567-6571)
引用
收藏
页码:6567 / 6571
页数:5
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