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An Update on FLT3 in Acute Myeloid Leukemia: Pathophysiology and Therapeutic Landscape

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Abstract

Purpose of Review

This review aims to summarize the pathophysiology, clinical presentation, and management of acute myeloid leukemia (AML) with FMS-like tyrosine kinase-3 (FLT3) mutations.

Recent Findings

The recent European Leukemia Net (ELN2022) recommendations re-classified AML with FLT3 internal tandem duplications (FLT3-ITD) as intermediate risk regardless of Nucleophosmin 1 (NPM1) co-mutation or the FLT3 allelic ratio. Allogeneic hematopoietic cell transplantation (alloHCT) is now recommended for all eligible patients with FLT3-ITD AML. This review outlines the role of FLT3 inhibitors in induction and consolidation, as well as for post-alloHCT maintenance. It outlines the unique challenges and advantages of assessing FLT3 measurable residual disease (MRD) and discusses the pre-clinical basis for the combination of FLT3 and menin inhibitors. And, for the older or unfit patient ineligible for upfront intensive chemotherapy, it discusses the recent clinical trials incorporating FLT3 inhibitors into azacytidine- and venetoclax-based regimens. Finally, it proposes a rational sequential approach for integrating FLT3 inhibitors into less intensive regimens, with a focus on improved tolerability in the older and unfit patient population.

Summary

The management of AML with FLT3 mutation remains a challenge in clinical practice. This review provides an update on the pathophysiology and therapeutic landscape of FLT3 AML, as well as a clinical management framework for managing the older or unfit patient ineligible for intensive chemotherapy.

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  1. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Rebecca Bystrom

  2. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA

    Mark J. Levis

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Rebecca Bystrom does not have any conflict of interest. Mark Levis is a consultant for Abbvie, Amgen, Astellas, Bristol Myers Squibb, Daiichi Sankyo, and Jazz and receives research funding from Astellas and FujiFilm.

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Bystrom, R., Levis, M.J. An Update on FLT3 in Acute Myeloid Leukemia: Pathophysiology and Therapeutic Landscape. Curr Oncol Rep 25, 369–378 (2023). https://doi.org/10.1007/s11912-023-01389-2

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