IDH1- and IDH2-mutated acute myeloid leukaemia: the decisions you may face
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.
Newly diagnosed IDH1-mutated, unfit for intensive chemotherapy
Ivosidenib plus azacitidine (AGILE) or venetoclax plus azacitidine; triplets in trials.
The first drug to block a mutant metabolic enzyme in cancer. With azacitidine it tripled survival in IDH1-mutated AML that could not take intensive chemotherapy.
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.
A pill that removes the survival shield from leukaemia cells, enabling chemotherapy-free, time-limited treatment for CLL.
- Tests Ivosidenib, AzacitidineNewly diagnosed IDH1-mutated AML unfit for intensive chemotherapy: ivosidenib + azacitidine vs placebo + azacitidine
OS 24.0 vs 7.9 months; HR 0.44.
- Tests Azacitidine, VenetoclaxNewly 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
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Differentiation syndrome · AGILE combination arm | 14% | - |
- 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.
| 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.
- Take with a meal and water. Avoid grapefruit, Seville oranges and starfruit.
- Reduce by 50% in severe impairment.
- Between Ivosidenib, Azacitidine and Venetoclax, 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 AGILE and 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 Ivosidenib or 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 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.
Add these to your appointment list, or take the full question set for this cancer.
Newly diagnosed, fit for intensive chemotherapy
7+3 induction with consolidation and transplant by ELN risk; IDH inhibitors added in trials.
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 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
The first drug to block a mutant metabolic enzyme in cancer. With azacitidine it tripled survival in IDH1-mutated AML that could not take intensive chemotherapy.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Treatment-related mortality 10-20%
- Chronic GVHD
- Relapse remains the main cause of failure
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Differentiation syndrome · AGILE combination arm | 14% | - |
- 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.
- Between Cytarabine + anthracycline ('7+3'), Allogeneic stem cell transplantation and Ivosidenib, 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.
- Which side effects of Ivosidenib 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 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.
Add these to your appointment list, or take the full question set for this cancer.
Relapsed or refractory
Ivosidenib or olutasidenib for IDH1, enasidenib for IDH2; venetoclax-based combinations; transplant in responders.
The first drug to block a mutant metabolic enzyme in cancer. With azacitidine it tripled survival in IDH1-mutated AML that could not take intensive chemotherapy.
Olutasidenib is a second IDH1 inhibitor for relapsed AML, with a higher response rate in its pivotal cohort than ivosidenib had in its own.
Enasidenib is the IDH2 counterpart of ivosidenib, approved in the US for relapsed disease but never approved in Europe after it failed to extend survival in a confirmatory trial.
A pill that removes the survival shield from leukaemia cells, enabling chemotherapy-free, time-limited treatment for CLL.
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
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Differentiation syndrome · AGILE combination arm | 14% | - |
- 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.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Differentiation syndrome | 16% | - |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Differentiation syndrome | 14% | - |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Take with a meal and water. Avoid grapefruit, Seville oranges and starfruit.
- Reduce by 50% in severe impairment.
- Treatment-related mortality 10-20%
- Chronic GVHD
- Relapse remains the main cause of failure
- Between Ivosidenib, Olutasidenib, Enasidenib 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.
- Which side effects of Ivosidenib or Olutasidenib 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: 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.
Add these to your appointment list, or take the full question set for this cancer.