The first 60 days: NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia
NPM1-mutated and KMT2A-rearranged leukaemias depend on a protein called menin to keep leukaemia genes switched on. Menin inhibitors, revumenib and ziftomenib, are the first drugs to exploit this, and they produce remissions in patients whose leukaemia had come back after everything else. Below, week by week, is what OnCo's record of NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
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.
Venetoclax plus azacitidine, with a menin inhibitor added in trials.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Newly diagnosed, fit for intensive chemotherapy.
- Medical oncologistNamed in the standard of care for: Newly diagnosed, fit for intensive chemotherapy, Newly diagnosed, unfit for intensive chemotherapy, Relapsed or refractory.
- Transplant and cell therapy teamNamed in the standard of care for: Newly diagnosed, fit for intensive chemotherapy, Relapsed or refractory.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Revumenib (KMT2A-rearranged or NPM1-mutated) or ziftomenib (NPM1-mutated) as a bridge to allogeneic transplant; menin inhibitor combinations in trials.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example NPM1 mutation and NPM1 transcript MRD, KMT2A rearrangement by FISH or RNA sequencing, FLT3-ITD co-mutation, MEN1 mutations, ELN 2022 risk group), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include NPM1-mutated AML without FLT3-ITD, NPM1-mutated AML with FLT3-ITD, KMT2A-rearranged AML.
- Is germline (inherited) genetic testing recommended for me or my family?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?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?Knowing the expected toxicities helps you plan work, family, and supportive care.
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?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?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of VIALE-A apply to someone like me?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?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?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?Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Revumenib, Ziftomenib, Bleximenib, Menin inhibitors?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?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?Supportive care improves quality of life and helps patients complete treatment.
- I read that “Whether a menin inhibitor added to first-line therapy raises cure rates in NPM1-mutated AML”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “MEN1 resistance mutations and how to sequence or combine inhibitors around them”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia: the full pageNPM1-mutated and KMT2A-rearranged leukaemias depend on a protein called menin to keep leukaemia genes switched on. Menin inhibitors, revumenib and ziftomenib, are the first drugs to exploit this, and they produce remissions in patients whose leukaemia had come back after everything else.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Differentiation syndrome: When a targeted drug makes leukaemia cells mature all at once, causing fever, fluid in the lungs, and weight gain.
- ELN 2022 risk classification: The three-tier system (favourable, intermediate, adverse) that decides how aggressively an adult with AML is treated and whether a transplant is recommended.
- Minimal / molecular residual disease (MRD): Cancer still present after treatment but too small to see on scans, detected by blood or marrow tests.
Every term links to the glossary.