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Inhibition of FLT3 in AML: a focus on sorafenib

Bone Marrow Transplantation volume 52, pages 344–351 (2017)Cite this article

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Abstract

FMS-like tyrosine kinase 3 (FLT3) is one of the most commonly mutated genes in AML. FLT3 is mutated in ~30% of patients with AML, either by internal tandem duplications (FLT3-ITD) of the juxta-membrane domain or by a point mutation, usually involving the tyrosine kinase domain. Several FLT3 tyrosine kinase inhibitors are being evaluated in multiple studies aiming at improving outcomes. The most widely used is sorafenib, a potent multikinase inhibitor approved for hepatocellular carcinoma and renal cell carcinoma. Sorafenib monotherapy or in combination with conventional chemotherapy, has been evaluated in various settings in AML, including front-line, relapsed or refractory disease including post-allograft failures and, more recently, as post-transplant maintenance therapy. Encouraging data have emerged with several other agents like lestaurtinib, midostaurin, crenolanib, gilteritinib and quizartinib. Although transient responses to FLT3 inhibitors are often observed in case of disease relapse, the most promising approach is the use of FLT3 inhibitors either in combination with induction chemotherapy or as consolidation/maintenance therapy after allogeneic hematopoietic cell transplantation. In this review, we summarize the clinical data on sorafenib and other FLT3 inhibitors in AML.

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Authors and Affiliations

  1. Department of Internal Medicine, Bone Marrow Transplantation Program, American University of Beirut Medical Center, Beirut, Lebanon

    A Antar, J El-Cheikh & A Bazarbachi

  2. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA

    Z K Otrock

  3. Department of Blood and Marrow Transplantation, H Lee Moffitt Cancer Center, Tampa, FL, USA

    M A Kharfan-Dabaja

  4. EBMT Paris Study Office/CEREST-TC, Paris, France

    G Battipaglia & M Mohty

  5. Department of Hematology, Saint Antoine Hospital, Paris, France

    G Battipaglia & M Mohty

  6. INSERM UMR 938, Université Pierre et Marie Curie, Paris, France

    G Battipaglia & M Mohty

  7. Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    R Mahfouz

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Antar, A., Otrock, Z., El-Cheikh, J. et al. Inhibition of FLT3 in AML: a focus on sorafenib. Bone Marrow Transplant 52, 344–351 (2017). https://doi.org/10.1038/bmt.2016.251

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  • DOI: https://doi.org/10.1038/bmt.2016.251

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