FLT3-mutated acute myeloid leukaemia

aka FLT3-ITD AML, FLT3-TKD AML, FLT3-positive AML

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.

Part ofAcute myeloid leukaemia

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.

The open questions are which inhibitor to pair with intensive chemotherapy, whether FLT3 inhibitor maintenance after transplant should be universal or MRD-guided (MORPHO found the gilteritinib benefit concentrated in patients with detectable FLT3-ITD before or after transplant), how to combine FLT3 inhibitors with venetoclax and azacitidine in unfit patients, and how to treat the resistance mutations and clonal switches that follow each drug.

State of the art

Gilteritinib turned relapsed FLT3-mutated AML from a chemotherapy-only setting into a targeted one.
Post-transplant FLT3 inhibitor maintenance is moving towards MRD-guided use.

Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

A FLT3 inhibitor with 7+3 is standard for every newly diagnosed FLT3-mutated patient fit for chemotherapy; RATIFY roughly tripled median survival.

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Fainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Gilteritinib Midostaurin Quizartinib source
Emergency services now
Bleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Azacitidine Cytarabine + anthracycline ('7+3')source
Emergency services now
Tumour lysis syndrome
Nausea, vomiting, muscle cramps, palpitations, seizures, confusion or passing much less urine in the first days of a new dose; the label requires hydration, anti-hyperuricaemic drugs and blood tests around each ramp-up step.
Venetoclax source
Check before combining
Quizartinib with Gilteritinib: major interaction
QT: both Quizartinib and Gilteritinib prolong the QT interval (known and known risk).. Boxed warning: QT prolongation, torsades and cardiac arrest. Do not start if QTcF above 450 ms; avoid QT-prolonging drugs; REMS programme.
Gilteritinib Quizartinib source
Check before combining
Food and drink: Midostaurin
Take with food; antiemetic prophylaxis.
Midostaurin source
Check before combining
Food and drink: Venetoclax
Take with a meal and water. Avoid grapefruit, Seville oranges and starfruit.
Venetoclax source

See all on the product pages:Azacitidine Cytarabine + anthracycline ('7+3')Gilteritinib Midostaurin Quizartinib Venetoclax·Printable cards in the navigator

Anatomy and lymph node drainage

Bone marrow, lymph nodes and spleen: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.

Subsites

Bone marrow (leukaemia, MDS, MPN, myeloma)FLT3-ITD AML (internal tandem duplication) · FLT3-TKD AML (D835 and other kinase domain point mutations) · FLT3-mutated AML with co-mutated NPM1
Lymph node germinal centre (lymphomas)
Spleen
Blood (leukaemic phase)
Lytic bone lesions (myeloma)
Skin and extranodal sites

Regional lymph nodes

cervical
axillary
mediastinal
para-aortic and mesenteric
inguinal

In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.

Same organ: Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis

Who gets it and what has changed

About three in ten adults with acute myeloid leukaemia carry a FLT3 mutation, most often the internal tandem duplication, which used to mark one of the worst outlooks in the disease.

Group

haematologic

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Lines of therapy by subgroup →Staging and risk scores →

Decisions you may face

3 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

Newly diagnosed, fit for intensive chemotherapy4 Newly diagnosed, unfit for intensive chemotherapy3 Relapsed or refractory3

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.

NCCN Guidelines: Acute Myeloid Leukemia

MidostaurinQuizartinibCytarabine + anthracycline ('7+3')RATIFY (CALGB 10603)QuANTUM-First Allogeneic stem cell transplantation FLT3 inhibitor + intensive chemotherapy

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.

NCCN Guidelines: Acute Myeloid Leukemia

VenetoclaxAzacitidineGilteritinibVIALE-A

Relapsed or refractory

Gilteritinib alone (ADMIRAL) as a bridge to allogeneic transplant; quizartinib where approved for relapse; FLT3 inhibitor maintenance after transplant.

NCCN Guidelines: Acute Myeloid Leukemia

GilteritinibADMIRALQuizartinibAllogeneic stem cell transplantation

Subtypes & biomarkers

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Subtypes

FLT3-ITD AML (internal tandem duplication)
FLT3-TKD AML (D835 and other kinase domain point mutations)
FLT3-mutated AML with co-mutated NPM1

Biomarkers clinicians test

FLT3-ITD and allelic ratio
FLT3-TKD (D835, I836)
NPM1 co-mutation
ELN 2022 risk group
FLT3-ITD MRD by NGS before and after transplant
Karyotype

How often this target appears

History

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1996FLT3 internal tandem duplications described in AML
FLT3
2017RATIFY: midostaurin with 7+3 lengthens life; first targeted AML drug approved
RATIFY (CALGB 10603)Midostaurin
2018Gilteritinib approved for relapsed FLT3-mutated AML after ADMIRAL
ADMIRALGilteritinib
2022ELN 2022 places all FLT3-ITD AML in intermediate risk
ELN 2022 risk classification
2023QuANTUM-First: quizartinib approved for FLT3-ITD AML up to age 75
QuANTUM-FirstQuizartinib

What changed

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Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.

All 13 changes by month →

FollowWatch this cancer and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for FLT3-mutated acute myeloid leukaemia, drawn from the whole corpus: 5 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.

Trials under way · 1

myeloMATCH · phase platform · NCI / National Clinical Trials Network

Trials reported · 3

ADMIRAL · phase 3 · 2019 · positive
QuANTUM-First · phase 3 · 2022 · positive
RATIFY (CALGB 10603) · phase 3 · 2017 · positive

Combinations being explored · 1

FLT3 inhibitor + intensive chemotherapy

Open problems and what is being done

Which FLT3 inhibitor to pair with intensive chemotherapy, and whether one inhibitor suits both ITD and TKD disease.
Whether post-transplant maintenance should be given to everyone or only to patients with detectable FLT3-ITD.
Resistance through FLT3 gatekeeper mutations and through loss of FLT3 dependence.
What is being done about this
Resistance to treatment
and how the field plans to fix it →
Available now
Small-molecule kinase inhibitorsStandard of care
In trials
Nothing recorded yet.
Ideas and roadmaps
Nothing recorded yet.
Also on OnCo: Resistance atlas · Lines of therapy.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

FLT3-mutated acute myeloid leukaemia

condition: FLT3-mutated acute myeloid leukemia

Open on ClinicalTrials.gov →

within

Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.

Landmark trials

ADMIRAL myeloMATCH QuANTUM-First RATIFY (CALGB 10603)VIALE-A

Expert centres

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Where the expertise is

Expert centres

9 centres in 4 countries · 1 with a trial for this cancer on record · second-opinion finder →

Choose a region from the globe in the header to mark centres near you.

9 centres


National Cancer Institute (NIH) Bethesda, MD · government	United States	none recorded	1	2,905	47,715	TIL therapy TCR-T cell therapy	-
USC Norris Comprehensive Cancer Center Los Angeles, CA · cancer center	United States	NCI comprehensive	0	318	3,917	Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)DNA methylation profiling	-
Walter and Eliza Hall Institute of Medical Research Melbourne · research institute	Australia	none recorded	0	298	3,639	CRISPR functional genomics Patient-derived organoids	-
Indiana University Melvin and Bren Simon Comprehensive Cancer Center Indianapolis, IN · cancer center	United States	NCI comprehensive	0	159	4,238	Platinum agents Cytotoxic chemotherapy Allogeneic stem cell transplantation	-
Juravinski Cancer Centre / Escarpment Cancer Research Institute Hamilton, ON · cancer center	Canada	none recorded	0	103	1,158	IMRT / IGRT (modern external beam)CAR-T cell therapy Allogeneic stem cell transplantation	-
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center Baltimore, MD · cancer center	United States	NCI comprehensive	0	101	2,306	Proton therapy SBRT / SABR (stereotactic radiotherapy)Allogeneic stem cell transplantation TCR-T cell therapy +1	-
Fred & Pamela Buffett Cancer Center Omaha, NE · cancer center	United States	NCI clinical	0	37	4,159	Allogeneic stem cell transplantation High-risk pancreatic surveillance (CAPS / PRECEDE)	-
HOVON Rotterdam · consortium	Netherlands	none recorded	0	8	207	MRD / molecular residual disease testing	-
Masonic Cancer Center, University of Minnesota Minneapolis, MN · cancer center	United States	NCI comprehensive	0	not matched	-	Allogeneic stem cell transplantation CAR-NK & CAR-macrophage Allogeneic (off-the-shelf) cell therapy	-

These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with FLT3-mutated acute myeloid leukaemia but is thinly recorded here will look small.

Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost. The second-opinion finder explains how referral works in your country.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about FLT3-mutated acute myeloid leukaemia

Generated from this cancer's standard of care, biomarkers, and pipeline · 18 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example FLT3-ITD and allelic ratio, FLT3-TKD, NPM1 co-mutation, ELN 2022 risk group, FLT3-ITD MRD by NGS before and after transplant), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include FLT3-ITD AML, FLT3-TKD AML, FLT3-mutated AML with co-mutated NPM1.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

Newly diagnosed, fit for intensive chemotherapy

For my situation (newly diagnosed, fit for intensive chemotherapy), which of the standard options do you recommend and why?
Why: Guideline options include: 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.
Am I a candidate for Midostaurin, Quizartinib, Cytarabine + anthracycline ('7+3'), and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of RATIFY (CALGB 10603) and QuANTUM-First apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Newly diagnosed, unfit for intensive chemotherapy

For my situation (newly diagnosed, unfit for intensive chemotherapy), which of the standard options do you recommend and why?
Why: Guideline options include: Venetoclax plus azacitidine, with a FLT3 inhibitor added in trials or where labelled; gilteritinib with azacitidine is an option.
Am I a candidate for Venetoclax, Azacitidine, Gilteritinib, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of VIALE-A apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Relapsed or refractory

For my situation (relapsed or refractory), which of the standard options do you recommend and why?
Why: Guideline options include: Gilteritinib alone (ADMIRAL) as a bridge to allogeneic transplant; quizartinib where approved for relapse; FLT3 inhibitor maintenance after transplant.
Am I a candidate for Gilteritinib, Quizartinib, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of ADMIRAL apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Any stage

Are there clinical trials I could join, for example of Gilteritinib, Quizartinib, Venetoclax, myeloMATCH?
Why: Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?
Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
Why: Supportive care improves quality of life and helps patients complete treatment.
I read that “Which FLT3 inhibitor to pair with intensive chemotherapy, and whether one inhibitor suits both ITD and TKD disease”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “Whether post-transplant maintenance should be given to everyone or only to patients with detectable FLT3-ITD”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.