Department of Hematology-Oncology, Hanyang University Hanmaeum Changwon Hospital, Changwon 51497, Korea.
Division of Hematology-Oncology, Department of Internal Medicine, Hanyang University College of Medicine, Hanyang University Seoul Hospital, Seoul 04763, Korea.
Int J Mol Sci. 2022 Oct 21;23(20):12708. doi: 10.3390/ijms232012708.
FLT3 mutations are the most common genomic alteration detected in acute myeloid leukemia (AML) with a worse clinical prognosis. The highly frequent FLT3 mutations, together with the side effects associated with clinical prognosis, make FLT3 promising treatment targets and have provoked the advancement of FLT3 inhibitors. Recently, numerous FLT3 inhibitors were actively developed, and thus the outcomes of this aggressive subtype of AML were significantly improved. Recently, midostaurin and gilteritinib were approved as frontline treatment of AML and as therapeutic agents in the recurred disease by the United States Food and Drug Administration. Recently, numerous promising clinical trials attempted to seek appropriate management in frontline settings, in relapsed/refractory disease, or after stem cell transplantation in AML. This review follows numerous clinical trials about the usefulness of FLT3 inhibitors as frontline therapy, as relapsed/refractory conditioning, and as maintenance therapy of stem cell transplantation. The cumulative data of FLT3 inhibitors would be important clinical evidence for further management with FLT3 inhibitors in AML patients with FLT3 mutations.
FLT3 突变是急性髓系白血病(AML)中最常见的基因组改变,具有更差的临床预后。高度频繁的 FLT3 突变,以及与临床预后相关的副作用,使 FLT3 成为有前途的治疗靶点,并推动了 FLT3 抑制剂的发展。最近,许多 FLT3 抑制剂被积极开发,因此这种侵袭性 AML 亚型的治疗结果得到了显著改善。最近,米哚妥林和吉特替尼被美国食品和药物管理局批准为 AML 的一线治疗药物和复发性疾病的治疗药物。最近,许多有前途的临床试验试图在 AML 的一线治疗、复发/难治性疾病或干细胞移植后寻找合适的管理方法。本综述跟踪了许多关于 FLT3 抑制剂作为一线治疗、复发/难治性疾病预处理以及干细胞移植维持治疗的临床试验。FLT3 抑制剂的累积数据将为 AML 患者中携带 FLT3 突变的患者进一步使用 FLT3 抑制剂治疗提供重要的临床证据。