Compassionate use of sorafenib in FLT3-ITD-positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation
Compassionate use of sorafenib in FLT3-ITD-positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation
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DOI：
10.1182/blood-2009-03-208298
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发表时间：
2009-06-25
期刊：
影响因子：
20.3
通讯作者：
Burchert, Andreas
中科院分区：
文献类型：
--
作者：
Metzelder, Stephan;Wang, Ying;Burchert, Andreas
FLT 3基因内部串联重复（ITD）突变的急性髓性白血病（AML）患者预后差。在这里，我们报告了多激酶和FLT 3-ITD抑制剂索拉非尼治疗复发性或难治性FLT 3-ITD阳性AML的同情使用结果。索拉非尼在同种异体干细胞移植（allo-SCT）之前（n = 2）、之后（n = 3）或之前和之后（n = 1）治疗的所有6例患者中均诱导了具有临床意义的非常快速的应答。索拉非尼诱导的缓解促进了3例难治性患者中2例的allo-SCT。在allo-SCT后接受治疗的4例患者中，有2例分别存活了216天和221天，而另外2例仍处于持续的完全分子缓解状态。索拉非尼反应与体内抗凋亡FLT 3-ITD靶点Stat-5的抑制相关。总之，在allo-SCT之前或之后，索拉非尼单药治疗在低风险FLT 3-ITD阳性AML中具有显著的临床活性，值得在前瞻性临床试验中进一步评估。（血。2009; 113：6567-6571）
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)