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

IF 6.1 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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引用次数: 0

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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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