IDH1- and IDH2-mutated acute myeloid leukaemia
IDH-mutated acute myeloid leukaemia has a faulty metabolic enzyme that floods cells with a chemical that blocks maturation. Pills that shut the enzyme off, ivosidenib for IDH1 and enasidenib or olutasidenib for IDH2 and IDH1, let the leukaemia cells mature, and ivosidenib with azacitidine tripled survival in older patients.
Overview
Mutant isocitrate dehydrogenase 1 or 2 makes the oncometabolite 2-hydroxyglutarate, which jams the DNA-demethylating enzymes that blood cells need to differentiate. IDH2 mutations (R140, R172) occur in roughly one in eight adult AML and IDH1 (R132) in about one in twelve. They co-occur with NPM1 and DNMT3A mutations and are enriched in older patients. Blocking the mutant enzyme does not kill the blast directly; it restores differentiation over weeks, and the price is differentiation syndrome in around a fifth of patients.
Enasidenib, approved in 2017 for relapsed or refractory IDH2-mutated AML on a phase 1/2 study, was the first IDH inhibitor; its phase 3 IDHENTIFY trial against conventional care in older relapsed patients did not lengthen survival. Ivosidenib followed in 2018 for relapsed IDH1-mutated disease and, after AGILE (2022), for newly diagnosed patients unfit for intensive chemotherapy: ivosidenib plus azacitidine gave a median overall survival of 24.0 months against 7.9 months with azacitidine alone (hazard ratio 0.44). Olutasidenib, a second IDH1 inhibitor, was approved for relapsed disease in 2022.
IDH-mutated leukaemias also respond unusually well to venetoclax with azacitidine, the VIALE-A subgroup showing the largest survival gain of any genotype, so the field now debates ivosidenib-azacitidine against venetoclax-azacitidine and tests triplets of all three. Resistance comes through second-site IDH mutations, isoform switching from IDH1 to IDH2, and emergence of RAS-pathway clones.
State of the art
- Three approved IDH inhibitors cover both genes in relapsed disease.
- Venetoclax-azacitidine is especially active in IDH-mutated leukaemia, so two targeted options compete in the same patients.
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.
- Ivosidenib plus azacitidine is a first-line standard for unfit IDH1-mutated patients after AGILE tripled median survival.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowDifferentiation syndrome
Fever, cough or breathlessness, rapid weight gain or swelling, bone pain, low blood pressure or reduced urine; the labels say to start steroids and monitor at the first suspicion, and the syndrome has been fatal.
- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowTumour 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.
- Check before combiningFood and drink: Venetoclax
Take with a meal and water. Avoid grapefruit, Seville oranges and starfruit.
- Check before combiningHeart rhythm (QT): Ivosidenib
Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
- Check before combiningLiver: Venetoclax
Reduce by 50% in severe impairment.
See all on the product pages:AzacitidineCytarabine + anthracycline ('7+3')EnasidenibIvosidenibOlutasidenibVenetoclax·Printable cards in the navigator
Anatomy and lymph node drainage
- Bone marrow (leukaemia, MDS, MPN, myeloma)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- Nodes: cervical
- Nodes: axillary
- Nodes: mediastinal
- Nodes: para-aortic and mesenteric
- Nodes: inguinal
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.
- Bone marrow (leukaemia, MDS, MPN, myeloma)IDH1 R132-mutated AML (ivosidenib, olutasidenib) · IDH2 R140- and R172-mutated AML (enasidenib) · IDH-mutated AML with NPM1 co-mutation · IDH-mutated secondary AML from myelodysplastic syndromes
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- 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), FLT3-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
About one in five adults with acute myeloid leukaemia carries a mutation in IDH1 or IDH2, more often in older patients and in leukaemia arising from a prior marrow disorder.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Ivosidenib plus azacitidine (AGILE) or venetoclax plus azacitidine; triplets in trials.
7+3 induction with consolidation and transplant by ELN risk; IDH inhibitors added in trials.
Ivosidenib or olutasidenib for IDH1, enasidenib for IDH2; venetoclax-based combinations; transplant in responders.
Subtypes & biomarkers
top- IDH1 R132-mutated AML (ivosidenib, olutasidenib)
- IDH2 R140- and R172-mutated AML (enasidenib)
- IDH-mutated AML with NPM1 co-mutation
- IDH-mutated secondary AML from myelodysplastic syndromes
- IDH1 R132 and IDH2 R140/R172 mutations
- 2-hydroxyglutarate level
- NPM1, DNMT3A and RAS co-mutations
- ELN 2022 risk group
- IDH mutation clearance as MRD
How often this target appears
- 2009IDH1 mutations found in AML after their discovery in glioma
- 2017Enasidenib: first IDH inhibitor approved, for relapsed IDH2-mutated AML
- 2018Ivosidenib approved for relapsed IDH1-mutated AML
- 2022AGILE: ivosidenib plus azacitidine lengthens life in newly diagnosed unfit patients; olutasidenib approved
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 12 changes by month →- 2026-09-17This recordIDH1- and IDH2-mutated acute myeloid leukaemiaFacts on this page last checked
When this page itself was last checked or edited.
- 2022ApprovalIvosidenibIvosidenib approved in US
Newly diagnosed IDH1-mutated AML with azacitidine (AGILE)
- 2022ApprovalOlutasidenibOlutasidenib approved in US
Relapsed/refractory IDH1-mutated AML
- 2022Trial resultAGILEAGILE reported
OS 24.
- 2022MilestoneAGILEAGILE: ivosidenib plus azacitidine lengthens life in newly diagnosed unfit patients; olutasidenib approved
A milestone in how this cancer is treated.
- 2020Trial resultVIALE-AVIALE-A reported
OS 14.
What is in development for IDH1- and IDH2-mutated acute myeloid leukaemia, drawn from the whole corpus: 2 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 · 1
- AGILE · phase 3 · 2022 · positive
Open problems and what is being done
Ivosidenib-azacitidine or venetoclax-azacitidine first, or all three together.
Managing differentiation syndrome without stopping an effective drug.
Isoform switching and second-site mutations that escape a single IDH inhibitor.
Trials
topTrials recruiting now
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
Expert centres
topExpert centres
Bethesda, MD · government | United States | none recorded | 1 | 2,905 | 47,715 | - | |
Singapore · cancer center | Singapore | none recorded | 0 | 493 | 5,212 | - | |
Los Angeles, CA · cancer center | United States | 0 | 318 | 3,917 | - | ||
Melbourne · research institute | Australia | none recorded | 0 | 298 | 3,639 | - | |
Singapore · hospital | Singapore | none recorded | 0 | 293 | 4,443 | - | |
Durham, NC · cancer center | United States | 0 | 204 | 6,303 | - | ||
Indianapolis, IN · cancer center | United States | 0 | 159 | 4,238 | - | ||
Hamilton, ON · cancer center | Canada | none recorded | 0 | 103 | 1,158 | - | |
Baltimore, MD · cancer center | United States | 0 | 101 | 2,306 | - | ||
Omaha, NE · cancer center | United States | 0 | 37 | 4,159 | - | ||
Rotterdam · consortium | Netherlands | none recorded | 0 | 8 | 207 | - | |
Minneapolis, MN · cancer center | United States | 0 | not matched | - | - | ||
Shanghai · hospital | China | none recorded | 0 | not matched | - | - |
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 IDH1- and IDH2-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.
Questions to ask
topQuestions to ask your oncologist about IDH1- and IDH2-mutated acute myeloid leukaemia
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 IDH1 R132 and IDH2 R140/R172 mutations, 2-hydroxyglutarate level, NPM1, DNMT3A and RAS co-mutations, ELN 2022 risk group, IDH mutation clearance as MRD), 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 IDH1 R132-mutated AML, IDH2 R140- and R172-mutated AML, IDH-mutated AML with NPM1 co-mutation.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Newly diagnosed IDH1-mutated, unfit for intensive chemotherapy
- For my situation (newly diagnosed idh1-mutated, unfit for intensive chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Ivosidenib plus azacitidine (AGILE) or venetoclax plus azacitidine; triplets in trials.
- Am I a candidate for Ivosidenib, Azacitidine, Venetoclax, 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 AGILE and VIALE-A apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
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 consolidation and transplant by ELN risk; IDH inhibitors added in trials.
- Am I a candidate for Cytarabine + anthracycline ('7+3'), Ivosidenib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Relapsed or refractory
- For my situation (relapsed or refractory), which of the standard options do you recommend and why?Why: Guideline options include: Ivosidenib or olutasidenib for IDH1, enasidenib for IDH2; venetoclax-based combinations; transplant in responders.
- Am I a candidate for Ivosidenib, Olutasidenib, Enasidenib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Olutasidenib, Venetoclax, myeloMATCH, Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)?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 “Ivosidenib-azacitidine or venetoclax-azacitidine first, or all three together”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Managing differentiation syndrome without stopping an effective drug”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with IDH1- and IDH2-mutated acute myeloid leukaemia, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
6targets
2drugs
6companies
5terms
3trials
3Latest papers
topQuery for this cancer: (TITLE:"IDH1- and IDH2-mutated acute myeloid leukaemia" OR ABSTRACT:"IDH1- and IDH2-mutated acute myeloid leukaemia" OR TITLE:"IDH-mutant AML" OR ABSTRACT:"IDH-mutant AML" OR TITLE:"IDH1-mutated AML" OR ABSTRACT:"IDH1-mutated AML" OR TITLE:"IDH2-mutated AML" OR ABSTRACT:"IDH2-mutated AML") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about IDH1- and IDH2-mutated acute myeloid leukaemia, not a curated reading list.
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