- A malignant disease, AML results from the abnormal proliferation and differentiation of myeloid stem cells in the bone marrow2
- AML is one of the most common forms of leukemia in adults2
- In AML, there are many mutations, but the most common is the FLT3 mutation, which includes ITD and TKD3
Among patients with diagnosed AML and identified mutations, approximately 1 in 3 may have a FLT3 mutation3
The FLT3-ITD mutation accelerates disease progression in AML1
The FLT3 mutation includes ITD and TKD, with ITD occurring the most frequently3
AML with FLT3-ITD mutations (without adverse-risk genetic lesions) is categorized as intermediate risk and is associated with poor prognosis1,4
FLT3-ITD mutations activate FLT3 kinase activity, resulting in proliferation and survival of myeloblasts in AML1
The unregulated proliferation of these cells, as well as their increased survival and lack of differentiation, may contribute to the development of AML2
The FLT3-ITD mutation adversely impacts outcomes in patients with AML compared to those without the mutation1,5
Shorter overall survival
Increased risk of relapse
About 75% of patients with FLT3-ITD+ AML at the time of diagnosis continue to have the ITD mutation at relapse, suggesting that FLT3-ITD may be responsible for disease progression.1
FLT3-ITD mutations have a negative prognostic
impact;
TKD mutations remain mostly an undefined factor in
prognosis1
FLT3-ITD is a driver mutation with a high leukemic burden1
OVER 10 YEARS, PATIENTS WITH FLT3-ITD MUTATIONS ARE
~50%
LESS LIKELY TO SURVIVE
COMPARED TO PATIENTS WITH FLT3-TKD MUTATIONS6
From a 2007 retrospective analysis of 1,107 adult patients with AML from the United Kingdom with a median age of 42 years, OS at 10 years in patients with FLT3-ITD and FLT3-TKD was 24% (n=257) and 51% (n=100), respectively (OR: 0.53 [95% CI: 0.41-0.69]; P<0.001, based on log-rank test).6
AML with FLT3-ITD mutations is categorized as intermediate risk.4
- In fact, FLT3-ITD mutations were the primary predictor of outcome in patients with intermediate-risk AML1,7
- Patients who received mutation-specific treatment had a higher rate of overall survival compared to standard therapy8
FLT3-ITD has a higher prevalence than FLT3-TKD and is identified as one of the the most common mutations in AML3
~80%
OF ALL FLT3 MUTATIONS ARE ITD+
In the United States, there are over 70,000 people living with AML, with more than 20,000 new cases estimated in 2024.9,10
Guidelines support prompt and comprehensive FLT3 mutation testing for all patients with AML1,4
Adult patients with confirmed or suspected AML should be tested for the FLT3-ITD mutation11
Molecular and cytogenetic analyses are important in helping to identify the appropriate treatment options4
An FDA-approved clinical study assay such as LeukoStrat® CDx FLT3 Mutation Assay is a direct way to identify FLT3-ITD mutations4,11
LeukoStrat® CDx FLT3 Mutation Assay has a turnaround time of 2-3 business days.12
Know the FLT3 mutation status. Know the risk.
ACT NOW.
AML=acute myeloid leukemia; CI=confidence interval; FLT3=FMS (feline McDonough sarcoma)–like tyrosine kinase 3; ITD=internal tandem duplication; OR=odds ratio; OS=overall survival; TKD=tyrosine kinase domain.
1. Daver N, Schlenk RF, Russell NH, Levis MJ. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019;33:299-312. doi:10.1038/s41375-018-0357-9 2. Vakiti A, Reynolds SB, Mewawalla P. Acute Myeloid Leukemia. In: StatPearls. Treasure Island (FL): StatPearls Publishing; April 27, 2024. 3. Patel PJ, Gönen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079-1089. doi:10.1056/NEJMoa1112304 4. Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377. doi:10.1182/blood.2022016867 5. Erba HP, Montesinos P, Kim HJ, et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. Published online: April 25, 2023. doi:10.1016/S0140-6736(23)00464-6 6. Mead AJ, Linch DC, Hills RK, Wheatley K, Burnett AK, Gale RE. FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. Blood. 2007;110(4):1262-1270. doi:10.1182/blood-2006-04-015826 7. Gale RE, Green C, Allen C, et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood. 2008;111(5):2776-2784. doi:10.1182/blood-2007-08-109090 8. Burd A, Levine RL, Ruppert AS, et al. Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial. Nat Med. 2020;26(12):1852-1858. doi:10.1038/s41591-020-1089-8 9. National Cancer Institute. Cancer stat facts: leukemia—acute myeloid leukemia (AML). Accessed November 6, 2023. https://seer.cancer.gov/statfacts/html/amyl.html 10. Siegel RL, Giaquinto AN, Jemal A. Cancer Statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. doi:10.3322/caac.21820 11. Arber DA, Borowitz MJ, Cessna M, et al. Initial diagnostic workup of acute leukemia: guideline from the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017;141(10):1342-1393. doi:10.5858/arpa.2016-0504-CP 12. LeukoStrat® CDx FLT3 Mutation Assay. San Diego, CA: Invivoscribe, Inc; 2017. Accessed August 31, 2023. https://invivoscribe.com/uploads/products/informationalDownloads/LabPMM-Flyer_Leukostrat-CDx_FLT3_8.5x11_20170420.pdf
