NPM1-mutated and KMT2A-rearranged 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

3 options

7+3 induction with consolidation; NPM1 MRD monitoring decides transplant in favourable-risk disease; transplant in first remission for KMT2A-rearranged and FLT3-ITD co-mutated disease.

Guideline

NCCN Guidelines: Acute Myeloid Leukemia

The options, in plain words

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

NGS-based MRD (clonoSEQ and molecular MRD)Standard of care

Sequencing the unique genetic barcode of a patient's leukaemia to find one cancer cell in a million.

10^-5 to 10^-6 sensitivity
Blood-based monitoring in many settings

Also referenced:ELN 2022 risk classification

The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record

Allogeneic stem cell transplantation

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

NGS-based MRD (clonoSEQ and molecular MRD)

Requires a baseline sample to identify the clone
Persisting pre-leukaemic clones (CHIP) confound AML MRD

Questions to ask about this decision

Between Cytarabine + anthracycline ('7+3'), Allogeneic stem cell transplantation and NGS-based MRD (clonoSEQ and molecular MRD), 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.
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 consolidation; NPM1 MRD monitoring decides transplant in favourable-risk disease; transplant in first remission for KMT2A-rearranged and FLT3-ITD co-mutated disease.
Am I a candidate for Cytarabine + anthracycline ('7+3'), and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

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

Special situations

Newly diagnosed, unfit for intensive chemotherapy

2 optionsCompare side by side →

Venetoclax plus azacitidine, with a menin inhibitor added in trials.

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.

Also referenced:Menin inhibitor + venetoclax + azacitidine

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.

Questions to ask about this decision

Between Venetoclax and Azacitidine, 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 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 menin inhibitor added in trials.
Am I a candidate for Venetoclax, Azacitidine, 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 →

Revumenib (KMT2A-rearranged or NPM1-mutated) or ziftomenib (NPM1-mutated) as a bridge to allogeneic transplant; menin inhibitor combinations in trials.

Guideline

NCCN Guidelines: Acute Myeloid Leukemia

The options, in plain words

RevumenibApprovedSmall-molecule menin inhibitor

Revumenib (Revuforj) is the first menin inhibitor (2024), for acute leukaemias with KMT2A rearrangements or NPM1 mutations.

ZiftomenibApprovedSmall-molecule menin inhibitor

Ziftomenib is the second menin inhibitor for leukaemia, approved in November 2025 as a once-daily pill for relapsed NPM1-mutated AML.

Allogeneic stem cell transplantationStandard of care

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

The evidence behind it

AUGMENT-101 Phase 1/2 NCT04065399 202494 peopleevidence 56
Tests Revumenib
Relapsed/refractory KMT2A-rearranged or NPM1-mutated acute leukaemia: revumenib monotherapy
CR+CRh 22.8%, ORR 63.2% in KMT2Ar cohort.
CR + CRh (KMT2Ar cohort) (%): Revumenib 22.8 (n=57) · source
KOMET-001 Phase 1/2 NCT04067336 2025112 peopleevidence 56
Tests Ziftomenib
Relapsed/refractory NPM1-mutated AML: ziftomenib 600 mg daily monotherapy
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.
CR 23%, ORR 33%, median OS 6.6 months.
Complete remission (%): Ziftomenib 23 (n=112) · source

The main trade-offs on record

Revumenib all recorded rates →

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

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 Revumenib, Ziftomenib 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 AUGMENT-101 and KOMET-001, 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.
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: Revumenib (KMT2A-rearranged or NPM1-mutated) or ziftomenib (NPM1-mutated) as a bridge to allogeneic transplant; menin inhibitor combinations in trials.
Am I a candidate for Revumenib, Ziftomenib, 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 AUGMENT-101 and KOMET-001 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.