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. 2024 Dec;103(12):5333-5340.
doi: 10.1007/s00277-024-06125-9. Epub 2024 Nov 30.

FLT3 inhibitors and hematopoietic cell transplantation prolong survival in patients with FLT3-ITD-positive AML

Toshihiro Matsukawa  1   2 , Masahiro Onozawa  3 , Takeshi Kondo  4 , Minoru Kanaya  4 , Daisuke Hidaka  5 , Shuichi Ota  5 , Akio Mori  4 , Akio Shigematsu  6 , Takuto Miyagishima  6 , Yasutaka Kakinoki  7 , Junichi Hashiguchi  8 , Satoshi Yamamoto  9 , Masayo Yamamoto  10 , Kentaro Wakasa  11 , Mutsumi Takahata  12 , Toshimichi Ishihara  13 , Yoshihito Haseyama  14 , Akihito Fujimi  15 , Tetsuya Igarashi  16 , Takehiro Sarashina  17 , Satoshi Iyama  18 , Ryoji Kobayashi  19 , Hajime Sakai  20 , Katsuya Fujimoto  21 , Junki Inamura  22 , Yuji Kanisawa  23 , Shinsuke Hirabayashi  24 , Tomoyuki Endo  3 , Daigo Hashimoto  3 , Takanori Teshima  3
Affiliations

FLT3 inhibitors and hematopoietic cell transplantation prolong survival in patients with FLT3-ITD-positive AML

Toshihiro Matsukawa et al. Ann Hematol. 2024 Dec.

Abstract

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with genetic alterations. The FMS-like tyrosine kinase 3 (FLT3) gene is frequently mutated in adult de novo AML, with two types of mutations: internal tandem duplication (ITD) and point mutations in the tyrosine kinase domain. This study aimed to investigate the impact of FLT3 inhibitors and hematopoietic cell transplantation (HCT) on survival outcomes in patients with FLT3-ITD AML in a real-world setting. We retrospectively analyzed 139 patients with FLT3-ITD-positive AML between 2012 and 2021. The median age was 63 years. In the propensity score-matched cohort, FLT3 inhibitors improved overall survival (OS) compared with patients treated without FLT3 inhibitors (3-year OS: 33.7% vs. 25.8%, p = 0.021). Patients who underwent HCT had superior outcomes to those without HCT (3-year OS: 45.3% vs. 2.2%, p < 0.0001). The combination of FLT3 inhibitors and HCT resulted in the highest OS and relapse-free survival (RFS) rates (3-year OS: 62.4%; 3-year RFS: 44.4%). Disease status before transplantation did not predict the prognosis, but use of FLT3 inhibitors increased survival in patients without complete remission before HCT. These results demonstrate the clinical impact of FLT3 inhibitors on survival outcomes in patients with FLT3-ITD-positive AML, particularly when combined with HCT. FLT3 inhibitors can improve the prognosis of AML with FLT3 mutations, especially in patients who undergo HCT.

Keywords: FLT3-ITD; Acute myeloid leukemia; FLT3 inhibitor; Hematopoietic cell transplantation.

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Conflict of interest statement

Declarations. Ethical approval: All procedures involving human participants were in accordance with the ethical standards of institutional research committees, national guidelines, and with the Declaration of Helsinki. This study was approved by the institutional review board of Hokkaido University Hospital (#022–0085). Competing interests: The authors declare no competing interests.

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