Mutation status should be a key consideration in your treatment strategy1-4

Molecular analysis can identify recurring gene fusions and acquired somatic mutations with prognostic value that may inform treatment pathways.2,3

Molecular analysis can also provide information on the allelic ratio or variant allele frequency (VAF) of a particular genetic mutation. This type of data can help further refine prognostic value and predictions of clinical outcomes.2,4,5

Timely molecular testing is crucial at diagnosis and should be considered at relapse6

Due to the potential for clonal evolution of acute myeloid leukemia (AML), the mutations present at relapse may differ from those detected at initial diagnosis.4,6-8 Thus, it is important to perform genetic testing multiple times over the course of a disease.

Diagnostic methods and techniques for molecular testing9-12

ELN guidelines recommend genetic testing, including
FLT3 mutations, at AML diagnosis.2 NCCN guidelines recommend
genetic testing, including FLT3 mutations, at diagnosis and relapse.1

AML, acute myeloid leukemia; ELN, European LeukemiaNet; FLT3, FMS-like tyrosine kinase 3; NCCN, National Comprehensive Cancer Network;
NGS, next-generation sequencing; PCR, polymerase chain reaction; TAT, turnaround time.

What does the future treatment landscape look like for AML?

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References
  1. National Comprehensive Cancer Network, Inc. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Acute Myeloid Leukemia. Version 3.2020. National Comprehensive Cancer Network, Inc, website. NCCN.org. Published December 23, 2019. Accessed February 3, 2020.
  2. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447.
  3. Bacher U, Schnittger S, Haferlach T. Molecular genetics in acute myeloid leukemia. Curr Opin Oncol. 2010;22(6):646-655.
  4. Warren M, Luthra R, Yin CC, et al. Clinical impact of change of FLT3 mutation status in acute myeloid leukemia patients. Mod Pathol. 2012;25(10):1405-1412.
  5. Dunlap JB, Leonard J, Rosenberg M, et al. The combination of NPM1, DNMT3A, and IDH1/2 mutations leads to inferior overall survival in AML. Am J Hematol. 2019;94(8):913-920.
  6. Shih L-Y, Huang C-F, Wu J-H, et al. Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples from 108 adult patients at diagnosis and relapse. Blood. 2002;100(7):2387-2392.
  7. Kottaridis PD, Gale RE, Langabeer SE, Frew ME, Bowen DT, Linch DC. Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors. Blood. 2002;100(7):2393-2398.
  8. Cloos J, Goemans BF, Hess CJ, et al. Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples. Leukemia. 2006;20(7):1217-1220.
  9. Kipp BR. The next generation of cancer testing: a quickly changing landscape fuels both optimism and pessimism. American Association for Clinical Chemistry website. https://www.aacc.org/publications/cln/articles/2016/october/the-next-generation-of-cancer-testing-a-quickly-changing-landscape-fuels-both-optimism-and-pessimism. Published October 1, 2016. Accessed September 19, 2018.
  10. Karlin-Neumann G. Improved liquid biopsies with combined digital PCR and next-generation sequencing. American Laboratory website. https://www.americanlaboratory.com/914-Application-Notes/183421-Improved-Liquid-Biopsies-With-Combined-Digital-PCR-and-Next-Generation-Sequencing/. Published February 19, 2016. Accessed September 19, 2018.
  11. Illumina, Inc. Benefits of NGS targeted resequencing (publication 770-2016-012). https://support.illumina.com/content/dam/illumina-marketing/documents/products/other/targeted-resequencing-guide-770-2016-012.pdf. Published 2017. Accessed September 19, 2018.
  12. Patnaik MM. The importance of FLT3 mutational analysis in acute myeloid leukemia [published online for public access]. Leuk Lymphoma. 2017:1-14. doi:10.1080/10428194.2017.1399312
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