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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
FLT3-mutated acute myeloid leukaemia carries a mutation in a growth-signal receptor that makes the leukaemia relapse quickly. Adding a FLT3 blocker to chemotherapy, midostaurin or quizartinib, lengthens life, and gilteritinib is the standard when the disease comes back.
FLT3 is a receptor tyrosine kinase on blood stem cells. An internal tandem duplication (ITD) in about a quarter of adult AML, or a point mutation in the tyrosine kinase domain (TKD) in under a tenth, keeps it switched on. FLT3-ITD leukaemias present with high white counts and relapse early, and the ELN 2022 classification places them in the intermediate-risk group whatever the allelic ratio, so an allogeneic transplant in first remission is usually recommended. Testing for FLT3 must return within days because the inhibitor is started with the first chemotherapy cycle.
RATIFY, reported in 2017, randomised 717 patients aged 18 to 59 to midostaurin or placebo added to 7+3 induction, consolidation and a year of maintenance: median overall survival rose from 25.6 to 74.7 months (hazard ratio 0.78), and midostaurin became the first targeted drug approved in AML that year. QuANTUM-First extended the approach to FLT3-ITD patients up to 75 with the more selective quizartinib: median survival 31.9 versus 15.1 months (hazard ratio 0.776), approved in 2023. For relapsed or refractory FLT3-mutated disease, ADMIRAL showed single-agent gilteritinib beat salvage chemotherapy, median survival 9.3 versus 5.6 months (hazard ratio 0.64), and it was approved in 2018.
| Setting | Approach | Guideline |
|---|---|---|
| Newly diagnosed, fit for intensive chemotherapy | 7+3 induction with midostaurin (RATIFY) or, for FLT3-ITD, quizartinib (QuANTUM-First), then consolidation and maintenance with the same inhibitor; allogeneic transplant in first remission for most FLT3-ITD patients. | not mapped |
| Newly diagnosed, unfit for intensive chemotherapy | Venetoclax plus azacitidine, with a FLT3 inhibitor added in trials or where labelled; gilteritinib with azacitidine is an option. | not mapped |
| Relapsed or refractory | Gilteritinib alone (ADMIRAL) as a bridge to allogeneic transplant; quizartinib where approved for relapse; FLT3 inhibitor maintenance after transplant. | not mapped |