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

IF 5.1 2区医学 Q1 ONCOLOGY Cancer Pub Date : 2025-03-17 DOI:10.1002/cncr.35813

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

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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.

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新诊断的fms样酪氨酸激酶3 （FLT3）突变的急性髓系白血病的时间和治疗方案的回顾性研究

fms样酪氨酸激酶3 （FLT3）突变，无论是内部串联重复（FLT3- itd）还是酪氨酸激酶结构域（FLT3- tkd），在急性髓性白血病（AML）中都很常见。FLT3-ITD预后不良。方法：作者进行了一项包括619例患者的回顾性研究，以评估不同治疗方案下新诊断的flt3突变AML的预后。结果：在接受强化化疗（IC）的FLT3- itd突变AML患者中，FLT3抑制剂（FLT3i）的添加与改善无复发生存的趋势相关（中位32.3个月vs. 14.3个月）；p = 0.055)和总生存期(OS；有FLT3i的35.5个月vs.无FLT3i的18.9个月；p = .098)。在接受低强度（LIT）方案的FLT3-ITD突变患者中，与接受其他治疗组合（单独使用LIT 11.2个月，LIT + FLT3i 9.2个月，LIT + venetoclax 10.3个月）的患者相比，三联体（LIT + FLT3i + venetoclax）的OS显着延长（19.1个月）。接受任何治疗的FLT3-ITD + NPM1共突变患者有改善OS的趋势(2年OS: 47% vs. 33%；p = .087)。FLT3-ITD等位基因比值；IDH1、IDH2、WT1、RUNX1和骨髓增生异常综合征相关突变；不良细胞遗传学对OS无显著影响。在具有里程碑意义的分析中，同种异体干细胞移植与接受IC的FLT3-ITD突变患者的OS改善趋势相关(接受同种异体干细胞移植和未接受同种异体干细胞移植的52.6个月和22.7个月；p = 0.076)，接受LIT的患者的OS有显著改善(38.6个月vs. 14.0个月，接受同种异体干细胞移植的vs.未接受同种异体干细胞移植的；p & lt;。)。结论FLT3i和同种异体干细胞移植是flt3突变AML患者的关键治疗方式。基于lit的三胞胎在ic不合格的患者中很有希望。

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来源期刊

Cancer 医学-肿瘤学

CiteScore

13.10

自引率

3.20%

发文量

480

审稿时长

2-3 weeks

期刊介绍： The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society. CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research