Why FLT3 matters:
AML diagnosis is complex, with a variety of possible mutations, but the most commonly detected single gene mutations are in the FLT3 gene, affecting approximately a third of newly diagnosed AML patients.1
FLT3 has two common mutation locations:1
- Internal tandem duplication (ITD) is the most common, affecting ~25–30% of patients, and is associated with a poor prognosis1 including earlier relapse and worse overall survival2
- Tyrosine kinase domain (TKD), affecting ~7%,1 with an unclear impact on prognosis3
Identifying FLT+ AML patients gives them the opportunity to benefit from targeted therapy with RYDAPT:4
- Increase in overall survival (median overall survival 25.6 months with placebo and SOC (95% CI, 31.5–NR) vs. 74.7 months with RYDAPT and SOC (95% CI, 18.6–42.9: p=0.009)*,4
Timely test results are essential
RYDAPT’s recommended protocol is based on a 7+3 induction chemotherapy schedule:
- Cytarabine Days 1–7, daunorubicin Days 1–3, with RYDAPT initiated on Day 8 where appropriate. This critical treatment window means that efficient testing turnaround times are essential.
Guidelines are also recognising the need for timely test results:
- The European LeukemiaNet (ELN) revised their guidelines for AML in 2017 recommending that FLT3 mutational screening should be available within 48 to 72 hours (at least in patients eligible for intensive chemotherapy)5
Choosing the right test for accurate results
There are a number of methods for identifying FLT3 mutations, but the current gold standard is PCR and fluorescence capillary electrophoresis. Test results need to:
- Be sensitive enough to show a minimum FLT3-ITD: FLT3-WT allelic ratio of 0.05*
- Be able to report both TKD and ITD mutations
Streamlining the test process
The testing process includes every step from requesting the test and shipping samples to getting the results. Some areas to consider that could be adjusted to allow the identification of FLT3+ patients in time for RYDAPT® initiation include:
- Requesting FLT3 testing on initial peripheral blood or bone marrow sample (consider reflex testing)
- What is the quickest way to send samples, whilst keeping them in the necessary condition?
- How can samples be marked to indicate that they should be processed as a priority?
- If batch testing is used, how can this be avoided/speeded up?
- Request that cytogenetic and molecular testing is done in parallel, and also that both TKD and ITD mutations are analysed simultaneously
- How are results available? Is it possible to call and get FLT3 analysis over the phone?
Your local Novartis Disease Area Specialist can coordinate a meeting with the laboratory to work out if/how current testing process can be changed to allow test results in time.
AML, acute myeloid leukaemia; CI, confidence interval; ELN, European LeukemiaNet; ITD, internal tandem duplication; NR, not reached; PCR, polymerase chain reaction; SOC, standard of care; TKD, tyrosine kinase inhibitor; WT, wild type.
* One-sided p by stratified log-rank test.
- Patel JP, Gönen M, Figueroa ME, et al. N Engl J Med. 2012;22;366(12):1079–1089.
- Kottaridis PD, Gale RE, Frew ME, et al. Blood. 2001;98(6):1752–1759.
- Mead AJ, Linch DC, Hills RK, et al. Blood. 2007;110(4):1262–1270.
- Stone RM, Mandrekar SJ, Sanford BL, et al. N Engl J Med. 2017;377(5):454–464.
- Döhner H, Estey E, Grimwade D, et al. Blood. 2017;129(4):424–447.