FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions

Antar, Ahmad I.; Otrock, Zaher K.; Jabbour, Elias; Mohty, Mohamad; Bazarbachi, Ali

doi:10.1038/s41375-019-0694-3

Cited by 243Acute Myeloid Leukemia ResearchRetinoids in leukemia and cellular processesChronic Myeloid Leukemia Treatments

FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions

Antar, Ahmad I., Otrock, Zaher K., Jabbour, Elias, Mohty, Mohamad, Bazarbachi, Ali·2020·Leukemia

DOI 10.1038/s41375-019-0694-3

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Abstract

The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in approximately one third of patients with acute myeloid leukemia (AML), either by internal tandem duplications (FLT3-ITD), or by a point mutation mainly involving the tyrosine kinase domain (FLT3-TKD). Patients with FLT3-ITD have a high risk of relapse and low cure rates. Several FLT3 tyrosine kinase inhibitors have been developed in the last few years with variable kinase inhibitory properties, pharmacokinetics, and toxicity profiles. FLT3 inhibitors are divided into first generation multi-kinase inhibitors (such as sorafenib, lestaurtinib, midostaurin) and next generation inhibitors (such as quizartinib, crenolanib, gilteritinib) based on their potency and specificity of FLT3 inhibition. These diverse FLT3 inhibitors have been evaluated in myriad clinical trials as monotherapy or in combination with conventional chemotherapy or hypomethylating agents and in various settings, including front-line, relapsed or refractory disease, and maintenance therapy after consolidation chemotherapy or allogeneic stem cell transplantation. In this practical question-and-answer-based review, the main issues faced by the leukemia specialists on the use of FLT3 inhibitors in AML are addressed.

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Two FLT-3 inhibitors (midostaurin and gilteritinib) have been approved by FDA for patients with FLT3-mutated AML.
“Several FLT-3 inhibitors have been tested in clinical trials and two (midostaurin and gilteritinib) of them have been approved by FDA for the patients with FLT3-mutated AML [129].”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [129]

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Authors: Antar, A. I., Otrock, Z. K., Jabbour, E., Mohty, M., & Bazarbachi, A.
Affiliations: Hammoud Hospital University Medical Center (LB)
Wayne State University (US)
The University of Texas MD Anderson Cancer Center (US)
Inserm (FR)
American University of Beirut Medical Center (LB)
Corresponding author: Bazarbachi, Ali
ORCID: Antar, Ahmad I.
Otrock, Zaher K.
Jabbour, Elias
Mohty, Mohamad
Bazarbachi, Ali
Venue: Leukemia
Publisher: Springer Science and Business Media LLC
Published: 2020-01-09
Volume: 34
Issue: 3
Pages: 682-696
ISSN: 0887-6924 (ISSN-L)
1476-5551
DOI: 10.1038/s41375-019-0694-3
OpenAlex: W3000653492
Cited by: 243
References: 105
Citations by year: 2026: 12 · 2025: 36 · 2024: 32 · 2023: 47 · 2022: 51 · 2021: 41 · 2020: 24
FWCI: 6.51
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Leukemia (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
Keywords: FLT3 inhibitors, acute myeloid leukemia, FLT3-ITD, FLT3-TKD, tyrosine kinase inhibitors, sorafenib, lestaurtinib, midostaurin, quizartinib, crenolanib, gilteritinib, multikinase inhibitor, relapse risk, maintenance therapy, allogeneic stem cell transplantation, hypomethylating agents, combination chemotherapy
MeSH terms: Sorafenib, Aniline Compounds, Antineoplastic Agents, Benzimidazoles, Carbazoles, Enzyme Inhibitors, Furans, Humans, Mutation, Neoplasm Recurrence, Local, Phenylurea Compounds, Piperidines, Prognosis, Pyrazines, Leukemia, Myeloid, Acute, Randomized Controlled Trials as Topic, Treatment Outcome, DNA Methylation, Staurosporine, fms-Like Tyrosine Kinase 3, Benzothiazoles

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