Post-allogeneic stem cell transplant FLT3- targeted maintenance therapy: updates and considerations for clinical practice.
Post-allogeneic stem cell transplant FLT3- targeted maintenance therapy: updates and considerations for clinical practice.
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DOI：
10.46439/stemcell.3.015
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Maziarz RT
中科院分区：
文献类型：
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作者：
Cohen J;Maziarz RT
急性髓系白血病 (AML) 的特点是多种分子和细胞遗传学异常，越来越多的数据支持临床和预后意义，以指导临床决策。描述得最多的突变之一涉及 fms 样酪氨酸激酶 3 (FLT3)，它会产生持续活跃的酪氨酸激酶，并且通常与不良预后相关，包括较短的总生存期和较高的复发率。靶向治疗的进步极大地影响了可用的治疗选择，而在过去的五年里，这种情况基本上没有改变。酪氨酸激酶抑制剂 (TKI)，特别是 FLT3 靶向疗法，现在已成为携带这种靶向突变的患者不可或缺的治疗选择。由于同种异体造血细胞移植 (alloHCT) 仍然是大多数成年 AML 患者的主要治疗方法，因此目标是让符合条件的患者进行移植。然而，即使对治疗产生深度反应的患者，alloHCT 后复发率仍然非常高。对 FLT3 靶向 TKI 作为 FLT3 阳性患者的 alloHCT 维持治疗的有限评估表明，随着正在进行的研究进一步调查第二代药物，结果有所改善，安全性也可耐受。因此，本评论旨在回顾alloHCT后FLT3靶向维持治疗的作用以及临床实践的注意事项。
Acute myeloid leukemia (AML) is characterized by multiple molecular and cytogenetic abnormalities, with increasing data to support clinical and prognostic implications to guide clinical decision making. One of the most well described mutations involves fms-like tyrosine kinase 3 (FLT3) that results in a constitutively active tyrosine kinase and is generally associated with poor prognosis involving shorter overall survival and higher rates of relapse. Advancements in targeted therapies have greatly influenced available treatment options in a landscape that has remained largely unchanged for the past five decades. Tyrosine kinase inhibitors (TKI), specifically FLT3-targeted therapies, are now integral treatment options for patients with this targetable mutation. As allogeneic hematopoietic cell transplant (alloHCT) remains the primary curative therapy for most adult AML patients, the goal is for eligible patients to proceed to transplant. However, post-alloHCT relapse remains exceedingly high even in patients achieving deep responses to therapy. Limited evaluation of FLT3-targeted TKIs as post-alloHCT maintenance therapy in FLT3-positive patients suggest improved outcomes and tolerable safety profiles, with ongoing studies further investigating second-generation agents. Thus, this commentary aims to review the role of post-alloHCT FLT3-targeted maintenance therapy and considerations for clinical practice.