FLT3-TKD (D835 and I836 tyrosine kinase domain mutations)

aka FLT3-TKD, FLT3 TKD, FLT3 D835, FLT3 D835Y, FLT3 I836, FLT3 tyrosine kinase domain mutation

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.

Part ofFLT3· FLT3Other readoutsFLT3-ITD All readouts

FLT3: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · FLT3 is a kinase mutated in about a third of acute myeloid leukaemias, where adding an inhibitor to chemotherapy improves survival.

Sequencing 2 approval thresholds

What it means for a patient

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.

Scoring rule

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

Thresholds used in approvals

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

Drugs whose label names it

Midostaurin Gilteritinib

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
LeukoStrat CDx FLT3 Mutation Assay	Invivoscribe Technologies	Acute Myelogenous Leukemia - Peripheral Blood or Bone Marrow	Midostaurin Gilteritinib	P160040 (04/28/2017)

Tests that measure it

LeukoStrat CDx FLT3 Mutation Assay FoundationOne Heme NeoGenomics NeoTYPE profiles