FLT3-mutated acute myeloid leukaemia: the decisions you may face

Cancer page →Second-opinion finder →

3 treatment settings, 3 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.

Advanced, first line

Newly diagnosed, fit for intensive chemotherapy

4 optionsCompare side by side →

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.

Guideline

NCCN Guidelines: Acute Myeloid Leukemia

The options, in plain words

MidostaurinApprovedSmall-molecule multikinase inhibitor (FLT3)

The first drug to improve survival in FLT3-mutated AML, added to standard chemotherapy: median survival went from about two years to more than six.

QuizartinibApprovedSmall-molecule kinase inhibitor (FLT3-ITD, type II)

Quizartinib is a more selective FLT3 blocker that, added to chemotherapy, roughly doubled median survival in the highest-risk FLT3 subtype.

Cytarabine + anthracycline ('7+3')Standard of careCytotoxic regimen

The intensive chemotherapy that has induced remission in fit AML patients since 1973: seven days of one drug, three of another. Still the backbone that targeted drugs are added to.

Allogeneic stem cell transplantationStandard of care

Allogeneic stem cell transplantation replaces a patient's blood system with a donor's after conditioning chemotherapy, so donor immune cells hunt down leukaemia left behind. It remains the only cure for adverse-risk acute myeloid leukaemia, high-risk acute lymphoblastic leukaemia and Richter transformation, at the price of graft-versus-host disease.

Curative for otherwise incurable leukaemia
Graft-versus-leukaemia is an antigen-agnostic immune therapy

Also referenced:FLT3 inhibitor + intensive chemotherapy

The evidence behind it

RATIFY (CALGB 10603)Phase 3 NCT00651261 2017717 peopleevidence 94
Tests Midostaurin, Cytarabine + anthracycline ('7+3')
Newly diagnosed FLT3-mutated AML, age 18-59: midostaurin vs placebo added to 7+3, consolidation, and one year of maintenance
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.
Median OS 74.7 vs 25.6 months; HR 0.78.
Overall survival (median) (months): Midostaurin + 7+3 74.7 (n=360) vs Placebo + 7+3 25.6 (n=357) · HR 0.78 · source
QuANTUM-First Phase 3 NCT02668653 2022539 peopleevidence 94
Tests Quizartinib, Cytarabine + anthracycline ('7+3')
Newly diagnosed FLT3-ITD AML, age 18-75: quizartinib vs placebo with 7+3, consolidation, and up to 3 years of maintenance
OS 31.9 vs 15.1 months; HR 0.776.
Overall survival (median) (months): Quizartinib + 7+3 31.9 (n=268) vs Placebo + 7+3 15.1 (n=271) · HR 0.776 · source

The main trade-offs on record

Midostaurin all recorded rates →

Side effect	Any grade	Grade 3+
Febrile neutropenia · Both arms of RATIFY; not drug-specific	-	84%

Take with food; antiemetic prophylaxis.
Possible QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Quizartinib all recorded rates →

Known QT prolongation. Boxed warning: QT prolongation, torsades and cardiac arrest. Do not start if QTcF above 450 ms; avoid QT-prolonging drugs; REMS programme.

Allogeneic stem cell transplantation

Treatment-related mortality 10-20%
Chronic GVHD
Relapse remains the main cause of failure

Questions to ask about this decision

Between Midostaurin, Quizartinib, Cytarabine + anthracycline ('7+3') and the other options, which do you recommend for me, and what about my case would make you choose differently?
Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
Why: The aim shapes how much side effect and disruption is worth accepting.
How closely do I match the people in RATIFY (CALGB 10603) and QuANTUM-First, and does that change what the results mean for me?
Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
Which side effects of Midostaurin are most likely for me, which are reversible, and which would make us stop?
Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
What happens if I delay, or decline this step for now? Is the decision reversible?
Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
Does your recommendation follow the current guideline (NCCN Guidelines: Acute Myeloid Leukemia), and if it departs from it, why?
Why: Departures from guidelines are sometimes right for an individual; they should be explained.
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.

Add these to your appointment list, or take the full question set for this cancer.

Special situations

Newly diagnosed, unfit for intensive chemotherapy

3 optionsCompare side by side →

Venetoclax plus azacitidine, with a FLT3 inhibitor added in trials or where labelled; gilteritinib with azacitidine is an option.

Guideline

NCCN Guidelines: Acute Myeloid Leukemia

The options, in plain words

VenetoclaxApprovedSmall-molecule BCL-2 inhibitor

A pill that removes the survival shield from leukaemia cells, enabling chemotherapy-free, time-limited treatment for CLL.

AzacitidineApprovedSmall-molecule hypomethylating agent (cytotoxic)

A gentle chemotherapy that switches silenced genes back on. With venetoclax it became the standard for older people with AML who cannot take intensive treatment.

GilteritinibApprovedSmall-molecule kinase inhibitor (FLT3, type I)

A single pill that beats salvage chemotherapy for relapsed FLT3-mutated AML, and the backbone of the triplets now being tested in frontline disease.

The evidence behind it

VIALE-A Phase 3 NCT02993523 2020443 peopleevidence 93
Tests Venetoclax, Azacitidine
Newly diagnosed AML unfit for intensive chemotherapy: venetoclax + azacitidine vs placebo + azacitidine
OS 14.7 vs 9.6 months, HR 0.66; CR 36.7% vs 17.9%.
Overall survival (median) (months): Venetoclax + azacitidine 14.7 (n=286) vs Placebo + azacitidine 9.6 (n=145) · HR 0.66 · source

The main trade-offs on record

Venetoclax all recorded rates →

Take with a meal and water. Avoid grapefruit, Seville oranges and starfruit.
Reduce by 50% in severe impairment.

Azacitidine all recorded rates →

Side effect	Any grade	Grade 3+
Neutropenia · VIALE-A combination arm	-	42%

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Gilteritinib all recorded rates →

Side effect	Any grade	Grade 3+
Differentiation syndrome · Boxed warning	3%	-

Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Questions to ask about this decision

Between Venetoclax, Azacitidine and Gilteritinib, which do you recommend for me, and what about my case would make you choose differently?
Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
Why: The aim shapes how much side effect and disruption is worth accepting.
How closely do I match the people in VIALE-A, and does that change what the results mean for me?
Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
Which side effects of Azacitidine or Gilteritinib are most likely for me, which are reversible, and which would make us stop?
Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
What happens if I delay, or decline this step for now? Is the decision reversible?
Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
Does your recommendation follow the current guideline (NCCN Guidelines: Acute Myeloid Leukemia), and if it departs from it, why?
Why: Departures from guidelines are sometimes right for an individual; they should be explained.
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.

Add these to your appointment list, or take the full question set for this cancer.

Third line and beyond

Relapsed or refractory

3 optionsCompare side by side →

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

Guideline

NCCN Guidelines: Acute Myeloid Leukemia

The options, in plain words

GilteritinibApprovedSmall-molecule kinase inhibitor (FLT3, type I)

A single pill that beats salvage chemotherapy for relapsed FLT3-mutated AML, and the backbone of the triplets now being tested in frontline disease.

QuizartinibApprovedSmall-molecule kinase inhibitor (FLT3-ITD, type II)

Quizartinib is a more selective FLT3 blocker that, added to chemotherapy, roughly doubled median survival in the highest-risk FLT3 subtype.

Allogeneic stem cell transplantationStandard of care

Curative for otherwise incurable leukaemia
Graft-versus-leukaemia is an antigen-agnostic immune therapy

The evidence behind it

ADMIRAL Phase 3 NCT02421939 2019371 peopleevidence 93
Tests Gilteritinib
Relapsed or refractory FLT3-mutated AML: gilteritinib monotherapy vs salvage chemotherapy
OS 9.3 vs 5.6 months; HR 0.64.
Overall survival (median) (months): Gilteritinib 9.3 (n=247) vs Salvage chemotherapy 5.6 (n=124) · HR 0.64 · source

The main trade-offs on record

Gilteritinib all recorded rates →

Side effect	Any grade	Grade 3+
Differentiation syndrome · Boxed warning	3%	-

Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Quizartinib all recorded rates →

Known QT prolongation. Boxed warning: QT prolongation, torsades and cardiac arrest. Do not start if QTcF above 450 ms; avoid QT-prolonging drugs; REMS programme.

Allogeneic stem cell transplantation

Treatment-related mortality 10-20%
Chronic GVHD
Relapse remains the main cause of failure

Questions to ask about this decision

Between Gilteritinib, Quizartinib and Allogeneic stem cell transplantation, which do you recommend for me, and what about my case would make you choose differently?
Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
Why: The aim shapes how much side effect and disruption is worth accepting.
How closely do I match the people in ADMIRAL, and does that change what the results mean for me?
Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
Which side effects of Gilteritinib are most likely for me, which are reversible, and which would make us stop?
Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
What happens if I delay, or decline this step for now? Is the decision reversible?
Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
Does your recommendation follow the current guideline (NCCN Guidelines: Acute Myeloid Leukemia), and if it departs from it, why?
Why: Departures from guidelines are sometimes right for an individual; they should be explained.
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.

Add these to your appointment list, or take the full question set for this cancer.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.