一项关于新诊断的、FMS样酪氨酸激酶3（FLT3）突变的急性髓系白血病患者跨时间和治疗方案的结局的回顾性研究。

A retrospective study of outcomes across time and treatment regimens in newly diagnosed, FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia.

作者信息

Bazinet Alexandre, Bataller Alex, Kadia Tapan, Daver Naval, Short Nicholas J, Yilmaz Musa, Sasaki Koji, DiNardo Courtney D, Borthakur Gautam M, Issa Ghayas, Bouligny Ian, Pierce Sherry, Garcia-Manero Guillermo, Ravandi Farhad, Kantarjian Hagop M

机构信息

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

出版信息

Cancer. 2025 Mar 15;131(6):e35813. doi: 10.1002/cncr.35813.

DOI:10.1002/cncr.35813

PMID:40097915

Abstract

BACKGROUND

FMS-like tyrosine kinase 3 (FLT3) mutations, either internal tandem duplications (FLT3-ITD) or tyrosine kinase domain (FLT3-TKD), are common in acute myeloid leukemia (AML). FLT3-ITD confers an adverse prognosis.

METHODS

The authors performed a retrospective study including 619 patients to evaluate outcomes in newly diagnosed FLT3-mutated AML across treatment regimens.

RESULTS

In patients with FLT3-ITD-mutated AML who received intensive chemotherapy (IC), the addition of a FLT3 inhibitor (FLT3i) was associated with trends toward improved relapse-free survival (median 32.3 vs. 14.3 months with vs. without a FLT3i; p = .055) and overall survival (OS; 35.5 vs. 18.9 months with vs. without a FLT3i; p = .098). In patients with FLT3-ITD mutations who received low-intensity (LIT) regimens, triplets (LIT plus a FLT3i plus venetoclax) were associated with significantly longer OS (19.1 months) compared with those who received other treatment combinations (11.2 months with LIT alone, 9.2 months with LIT plus FLT3i, and 10.3 months with LIT plus venetoclax). Patients with FLT3-ITD plus NPM1 co-mutations who received any therapy had a trend toward improved OS (2-year OS: 47% vs. 33%; p = .087). The FLT3-ITD allelic ratio; IDH1, IDH2, WT1, RUNX1, and myelodysplastic syndrome-related mutations; and adverse cytogenetics had no significant impact on OS. In landmark analyses, allogeneic stem cell transplantation was associated with a trend toward improved OS in patients with FLT3-ITD mutations who received IC (52.6 vs. 22.7 months with versus without allogeneic stem cell transplantation; p = .076) and a marked improvement in OS in those who received LIT (38.6 vs. 14.0 months with vs. without allogeneic stem cell transplantation; p < .0001).

CONCLUSIONS

A FLT3i and allogeneic stem cell transplantation are key treatment modalities for patients who have FLT3-mutated AML. LIT-based triplets are promising in IC-ineligible patients.

摘要

背景

FMS样酪氨酸激酶3（FLT3）突变，即内部串联重复（FLT3-ITD）或酪氨酸激酶结构域（FLT3-TKD），在急性髓系白血病（AML）中很常见。FLT3-ITD预示着不良预后。

方法

作者进行了一项回顾性研究，纳入619例患者，以评估新诊断的FLT3突变AML患者在不同治疗方案下的预后。

结果

在接受强化化疗（IC）的FLT3-ITD突变AML患者中，添加FLT3抑制剂（FLT3i）与无复发生存期改善趋势相关（有FLT3i组中位无复发生存期为32.3个月，无FLT3i组为14.3个月；p = 0.055），总生存期（OS）也有改善趋势（有FLT3i组为35.5个月，无FLT3i组为18.9个月；p = 0.098）。在接受低强度（LIT）方案的FLT3-ITD突变患者中，三联方案（LIT加FLT3i加维奈托克）与显著更长的OS相关（19.1个月），相比接受其他治疗组合的患者（单纯LIT组为11.2个月，LIT加FLT3i组为9.2个月，LIT加维奈托克组为10.3个月）。接受任何治疗的FLT3-ITD与NPM1共突变患者有OS改善趋势（2年OS：47%对33%；p = 0.087）。FLT3-ITD等位基因比率、异柠檬酸脱氢酶1（IDH1）、异柠檬酸脱氢酶2（IDH2）、威尔姆斯瘤1（WT1）、 runt相关转录因子1（RUNX1）以及与骨髓增生异常综合征相关的突变和不良细胞遗传学对OS无显著影响。在标志性分析中，异基因干细胞移植与接受IC的FLT3-ITD突变患者的OS改善趋势相关（有与无异基因干细胞移植组分别为52.6个月对22.7个月；p = 0.076），在接受LIT的患者中OS有显著改善（有与无异基因干细胞移植组分别为38.6个月对14.0个月；p < 0.0001）。