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FLT3-ITD. Clinical (Sorafenib/AC220)

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Targeted Therapy of Acute Myeloid Leukemia

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

A plethora of new molecular abnormalities has been identified to be associated with acute myelogenous leukemia (AML). These markers have contributed to a more accurate prognostic stratification of these patients, and have nurtured hopes for effective targeted therapies. One such abnormality is the FMS-like tyrosine kinase 3, or FLT3 gene mutation, present in approximately 30 % of AML patients. The presence of the FLT3 internal tandem duplication (FLT3-ITD) confers a poorer prognosis with higher risk of relapse for this subset of AML patients. Rapid development of a large number of FLT3 tyrosine kinase inhibitors (TKIs) has enabled an exciting era of research and treatment for patients with these abnormalities. The expectation is that FLT3 inhibition may offer improvements in outcomes in this poor prognosis group of patients. Early data suggest that this promise may be materializing for patients. This chapter will focus on two of these FLT3 inhibitors, sorafenib (Nexavar®) and AC220 (quizartinib).

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Authors and Affiliations

  1. Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcomb Boulevard Suite R81000, 77030, Houston, TX, USA

    Jorge Eduardo Cortes M.D.

  2. Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0428, 77030, Houston, TX, USA

    Naveen Pemmaraju M.D.

Authors
  1. Naveen Pemmaraju M.D.
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  2. Jorge Eduardo Cortes M.D.
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Correspondence to Jorge Eduardo Cortes M.D. .

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Editors and Affiliations

  1. Dept. Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Michael Andreeff

Conclusion

Conclusion

The standard backbone of treatment for AML (i.e., anthracycline- and cytarabine-based therapies) has remained largely unchanged over the past 40 years, and outcomes remain overall poor in this hematologic malignancy. Therapeutic strategies inhibiting the kinase activity of FLT3 in patients with AML with FLT3 mutations have yielded promising results thus far, as this approach represents one of the first attempts at rational, biologically based personalized treatment in patients with AML. However, significant challenges still remain as most of the responses are transient and mechanisms of resistance need to be overcome and discovered. The optimal ways to combine FLT3 inhibitors with other agents need to be investigated and is likely to vary from patient to patient. Further translational and clinical research is warranted to continue to investigate FLT3 inhibitors in the clinic with particular attention to the biology of FLT3 and better characterization of the various mechanisms of FLT3 resistance. Still, FLT3 inhibitors are likely to become an important tool in our quest to conquer AML.

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Pemmaraju, N., Cortes, J. (2015). FLT3-ITD. Clinical (Sorafenib/AC220). In: Andreeff, M. (eds) Targeted Therapy of Acute Myeloid Leukemia. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1393-0_12

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  • DOI: https://doi.org/10.1007/978-1-4939-1393-0_12

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