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FLT3-TKD mutations are point changes in the kinase's activation loop, found in about 7 percent of acute myeloid leukaemias. Midostaurin and gilteritinib labels cover them; quizartinib's does not.
D835 substitutions and I836 deletions in exon 20 activate FLT3 without the duplication seen in ITD; their prognostic weight is neutral in ELN 2022. The LeukoStrat CDx assay detects D835 and I836 alongside ITD, which is why midostaurin (newly diagnosed 'FLT3 mutation-positive' AML) and gilteritinib (relapsed or refractory 'with a FLT3 mutation') cover TKD mutations, while quizartinib is labelled for FLT3-ITD only. TKD mutations, especially D835, also arise as resistance to type II inhibitors such as quizartinib and sorafenib.
In plain words · FLT3 is a kinase mutated in about a third of acute myeloid leukaemias, where adding an inhibitor to chemotherapy improves survival.
A FLT3-TKD mutation means midostaurin can be added to your first chemotherapy and gilteritinib is on label if the leukaemia returns; quizartinib is not approved for TKD-only disease. A TKD mutation that appears later, during treatment with quizartinib, is a sign of resistance and a reason to switch.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
A FLT3 D835 or I836 mutation in the tyrosine kinase domain by the LeukoStrat CDx assay or sequencing of blood or marrow.
“ITD mutations and TKD mutations D835 and I836”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| FLT3 mutation-positive (includes TKD) | Midostaurin | FLT3-mutated acute myeloid leukaemia | FDA | label |
| FLT3 mutation (includes TKD), relapsed or refractory | Gilteritinib | FLT3-mutated acute myeloid leukaemia | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| LeukoStrat CDx FLT3 Mutation Assay | Invivoscribe Technologies | Acute Myelogenous Leukemia - Peripheral Blood or Bone Marrow | MidostaurinGilteritinib | P160040 (04/28/2017) |
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