Sorafenib Maintenance Appears Safe and Improves Clinical Outcomes in FLT3-ITD Acute Myeloid Leukemia After Allogeneic Hematopoietic Cell Transplantation
Sorafenib Maintenance Appears Safe and Improves Clinical Outcomes in FLT3-ITD Acute Myeloid Leukemia After Allogeneic Hematopoietic Cell Transplantation
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DOI：
10.1016/j.clml.2014.12.005
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发表时间：
2015-05-01
影响因子：
2.7
通讯作者：
Bazarbachi, Ali
中科院分区：
文献类型：
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作者：
Antar, Ahmad;Kharfan-Dabaja, Mohamed A.;Bazarbachi, Ali
我们报告了6例FLT 3-ITD急性髓系白血病（AML）患者在异基因造血细胞移植（allo-HCT）后成功使用索拉非尼。所有患者均存活，自索拉非尼开始后中位随访12个月（范围，4-20个月）时完全缓解。这些发现证明了在allo-HCT.Background后使用索拉非尼维持治疗FLT 3-ITD AML的更广泛的临床评价：FMS样酪氨酸激酶3内部串联重复（FLT 3-ITD）基因是急性髓系白血病（AML）中最常见的遗传改变之一，发病率约为20%至30%。FLT 3-ITD与不良结局显著相关，建议对携带该突变的患者进行异基因造血细胞移植（allo-HCT）。索拉非尼是一种对RAF、VEGF和FLT 3-ITD有活性的酪氨酸激酶抑制剂。它已在FLT 3-ITD AML中以标签外方式使用。患者和方法：我们回顾性评估了在FLT 3-ITD AML患者中allo-HCT后成功使用索拉非尼的情况。6例FLT 3-ITD AML患者接受索拉非尼作为移植后维持治疗（n = 5）或在allo-HCT后复发（n = 1）后作为挽救治疗，并在之后继续治疗。结果：1例患者在开始索拉非尼治疗后100天发生心肌梗死。有趣的是，在6例患者中的5例中观察到皮肤移植物抗宿主病（II级），并且通常在开始索拉非尼治疗后几天内发生，但所有患者对皮质类固醇治疗均迅速反应。所有6例患者均存活，自首次诱导后中位随访16个月（范围，10-29个月），自索拉非尼开始后中位随访12个月（范围，4-20个月）时完全缓解。值得注意的是，所有患者的疾病均处于分子缓解期。结论：索拉非尼似乎是FLT 3-ITD AML患者allo-HCT后的有效维持治疗，可实现持久的完全缓解。这表明索拉非尼在移植后环境中具有免疫调节作用，并需要对维持索拉非尼在FLT 3-ITD AML中的应用进行更广泛的临床评价。(C)2015 Elsevier Inc. All rights reserved.
We report the successful use of sorafenib after allogeneic hematopoietic cell transplantation (allo-HCT) in 6 patients with FLT3-ITD acute myeloid leukemia (AML). All patients were alive and in complete remission at a median follow-up of 12 months (range, 4-20 months) since initiation of sorafenib. These findings warrant a broader clinical evaluation of the use of maintenance sorafenib in FLT3-ITD AML after allo-HCT.Background: The FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) gene is one of the most frequently observed genetic alterations in acute myeloid leukemia (AML), with an incidence of about 20% to 30%. FLT3-ITD is significantly associated with a poor outcome, and offering an allogeneic hematopoietic cell transplantation (allo-HCT) is recommended for patients harboring this mutation. Sorafenib is a tyrosine kinase inhibitor active against RAF, VEGF, and FLT3-ITD. It has been used in an off-label fashion in FLT3-ITD AML. Patients and Methods: We retrospectively assessed the successful use of sorafenib after allo-HCT in patients with FLT3-ITD AML. Six FLT3-ITD AML patients received sorafenib as posttransplantation maintenance therapy (n = 5) or as salvage therapy after a post-allo-HCT relapse (n = 1) and continued afterward. Results: One patient developed myocardial infarction 100 days after initiation of sorafenib. Interestingly, skin graft versus host disease (grade II) was observed in 5 of 6 patients and generally occurred within few days after initiation of sorafenib, but it responded promptly to corticosteroid therapy in all patients. All 6 patients were alive and in complete remission at a median follow-up of 16 months (range, 10-29 months) since first induction and at a median follow-up of 12 months (range, 4-20 months) since initiation of sorafenib. Remarkably, the disease of all patients was in molecular remission. Conclusion: Sorafenib appears to be an effective maintenance therapy after allo-HCT in FLT3-ITD AML, with achievement of durable complete responses. This suggests an immunomodulatory effect of sorafenib in the posttransplantation setting and warrants a broader clinical evaluation of the use of maintenance sorafenib in FLT3-ITD AML. (C) 2015 Elsevier Inc. All rights reserved.