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FLT3-targeted treatment for acute myeloid leukemia

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Abstract

Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene are detected in approximately 30% of acute myeloid leukemia (AML). The high frequency of FLT3 mutations, along with their adverse effect on prognosis, makes FLT3 a promising therapeutic target, and has spurred development of FLT3 inhibitors. First-generation inhibitors, including midostaurin and sorafenib, lack specificity for FLT3 and act on multiple kinases, whereas second-generation inhibitors, including gilteritinib, and quizartinib, are highly specific to FLT3 and are more potent than first-generation inhibitors. Several FLT3 inhibitors have recently gained regulatory approval worldwide, and several others are under development. The advent of FLT3 inhibitors has changed the standard treatment for FLT3-mutated AML in the frontline and relapsed/refractory settings and contributed to improved outcomes for this formidable AML subtype. However, numerous unresolved issues remain owing to rapid changes in practice. These include identification of optimum FLT3 inhibitors and combination therapies, the role of maintenance therapy, and the indication for allogeneic hematopoietic cell transplantation. Furthermore, strategies to overcome resistance to FLT3 inhibitors must be pursued. Results of ongoing and future studies will improve our ability to use FLT3 inhibitors more effectively, which should provide significant benefits to a wider range of patients.

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Acknowledgements

This work was supported in part by the National Cancer Research and Development expenses grant, grant number: 2021-A-11 (YM), and the Aichi Cancer Research Foundation, grant number: 2021-1-19 (MY).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Yasuyuki Arai

  2. Department of Hematology, National Cancer Center Hospital East, Kashiwa, Japan

    SungGi Chi & Yosuke Minami

  3. Department of Hematology and Cell Therapy, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Masamitsu Yanada

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  1. Yasuyuki Arai
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  2. SungGi Chi
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Correspondence to Masamitsu Yanada.

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YM received honoraria from Bristol-Myers Squibb, Novartis, and Pfizer. MY received research funding from AbbVie and Novartis; and honoraria from AbbVie, Daiichi Sankyo, and Kyowa Kirin.

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Arai, Y., Chi, S., Minami, Y. et al. FLT3-targeted treatment for acute myeloid leukemia. Int J Hematol 116, 351–363 (2022). https://doi.org/10.1007/s12185-022-03374-0

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