# Acute myeloid leukaemia in older or unfit patients

Source: https://onco.cc/cancers/aml-older-unfit/  
OnCo record `aml-older-unfit` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Most people with acute myeloid leukaemia are over 65, and many cannot take intensive chemotherapy. Venetoclax with azacitidine, two gentler drugs, doubled remission rates and lengthened life in this group, replacing the old choice between supportive care and low-dose chemotherapy.

## Summary

Fitness for intensive induction is judged on age, performance status, organ function and comorbidity (the Ferrara criteria and geriatric assessment) rather than on a birthday. Older patients also carry worse biology: more adverse karyotypes, TP53 mutations and secondary disease, and fewer favourable NPM1 or core-binding-factor leukaemias. Until 2018 the options were azacitidine or decitabine alone, low-dose cytarabine or supportive care, with median survival under a year.

VIALE-A, reported in 2020, randomised 431 newly diagnosed patients unfit for intensive therapy to venetoclax or placebo with azacitidine: composite complete remission 66.4 percent versus 28.3 percent, median overall survival 14.7 versus 9.6 months (hazard ratio 0.66), and 37.5 percent versus 16.7 percent alive at two years on longer follow-up. The benefit was largest in IDH-mutated and NPM1-mutated disease and smallest in TP53-mutated and FLT3-ITD disease. Venetoclax-azacitidine received full approval in 2020 and is the global standard; glasdegib with low-dose cytarabine is a lesser alternative, and ivosidenib-azacitidine competes in IDH1-mutated disease.

The regimen brings its own problems: prolonged neutropenia and infections, cycles that must be shortened or delayed, tumour lysis at the start, and azole antifungals that raise venetoclax levels. Current trials shorten the venetoclax course, add FLT3, IDH or menin inhibitors as triplets, take responders to reduced-intensity transplant, and test whether some fit older patients do better with venetoclax-azacitidine than with 7+3.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Unfit AML; AML in the elderly; AML ineligible for intensive chemotherapy; Low-intensity AML therapy
- Tags: subtype-page
- Group: haematologic
- Burden: The median age at diagnosis of acute myeloid leukaemia is about 68, and roughly half of patients are judged unable to withstand intensive chemotherapy because of age, frailty or other illnesses.
- Subtypes: Newly diagnosed AML unfit for intensive chemotherapy (age 75 or over, or comorbidity); AML in fit older patients (60 to 75) eligible for intensive therapy or CPX-351; IDH- or NPM1-mutated AML in unfit patients (best responders to venetoclax-azacitidine); TP53-mutated AML in unfit patients; Relapsed AML after venetoclax-azacitidine
- Biomarkers: Performance status and geriatric assessment; Comorbidity index and organ function; ELN 2022 risk group; IDH1/2, NPM1, FLT3 and TP53 mutations; Measurable residual disease by flow cytometry; Azole co-medication (venetoclax dose)

## Standard of care

- Newly diagnosed, unfit for intensive chemotherapy: Venetoclax plus azacitidine (VIALE-A) or venetoclax plus decitabine; ivosidenib plus azacitidine for IDH1-mutated disease; targeted triplets in trials. ([Venetoclax](https://onco.cc/drugs/venetoclax/), [Azacitidine](https://onco.cc/drugs/azacitidine/), [Decitabine](https://onco.cc/drugs/decitabine/), [VIALE-A](https://onco.cc/trials/viale-a/), [Ivosidenib](https://onco.cc/drugs/ivosidenib/), [AGILE](https://onco.cc/trials/agile/), [Venetoclax + hypomethylating agent](https://onco.cc/pairings/venetoclax-plus-hma/))
- Fit older patients, 60 to 75: 7+3 or CPX-351 for secondary disease, with a FLT3 inhibitor where indicated, and reduced-intensity allogeneic transplant in remission. ([Cytarabine + anthracycline ('7+3')](https://onco.cc/drugs/cytarabine-7-3/), [CPX-351 (liposomal daunorubicin-cytarabine)](https://onco.cc/drugs/cpx-351/), [Midostaurin](https://onco.cc/drugs/midostaurin/), [Quizartinib](https://onco.cc/drugs/quizartinib/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))
- Not a candidate for any leukaemia-directed therapy: Hydroxyurea for count control, transfusion support and palliative care; low-dose cytarabine or glasdegib combinations where tolerated. ([Hydroxyurea (hydroxycarbamide)](https://onco.cc/drugs/hydroxyurea/), [Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/), [Glasdegib](https://onco.cc/drugs/glasdegib/), [Cytarabine](https://onco.cc/drugs/cytarabine/))
- Relapse after venetoclax-azacitidine: Genotype-directed drugs (gilteritinib, IDH inhibitors, menin inhibitors) or trials; transplant for the few who respond. ([Gilteritinib](https://onco.cc/drugs/gilteritinib/), [Ivosidenib](https://onco.cc/drugs/ivosidenib/), [Revumenib](https://onco.cc/drugs/revumenib/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))

## State of the art

- Venetoclax with azacitidine is the worldwide standard for unfit newly diagnosed patients, giving remission to two in three.
- Geriatric assessment, not age alone, decides fitness for intensive treatment.
- Reduced-intensity transplant after low-intensity remission is extending cure to patients in their seventies.

## Open problems

- How long venetoclax needs to be given, and whether MRD-negative patients can stop.
- Whether fit older patients do better with venetoclax-azacitidine than with intensive chemotherapy.
- Infections and cytopenias that keep older patients in hospital during a treatment meant to be gentle.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Acute_myeloid_leukemia
- Wikipedia: https://en.wikipedia.org/wiki/Acute_myeloid_leukemia
- NCCN Guidelines: Acute Myeloid Leukemia: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1411

## Connected records

- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [BCL-2 inhibitors](https://onco.cc/technologies/bcl2-inhibitors/), [G8 geriatric screening tool](https://onco.cc/technologies/g8-geriatric-screening/), [Geriatric assessment](https://onco.cc/technologies/geriatric-assessment/), [Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/)
- targets: [BCL-2](https://onco.cc/targets/bcl2/)
- pathways: [Intrinsic apoptosis (BCL-2 family)](https://onco.cc/pathways/apoptosis-bcl2/)
- terms: [ELN 2022 risk classification](https://onco.cc/terms/eln-risk/), [Hypomethylating agents (azacitidine, decitabine)](https://onco.cc/terms/hma/), [Tumour lysis syndrome (TLS)](https://onco.cc/terms/tumor-lysis-syndrome/)
- drugs: [Azacitidine](https://onco.cc/drugs/azacitidine/), [CPX-351 (liposomal daunorubicin-cytarabine)](https://onco.cc/drugs/cpx-351/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Cytarabine + anthracycline ('7+3')](https://onco.cc/drugs/cytarabine-7-3/), [Decitabine](https://onco.cc/drugs/decitabine/), [Gilteritinib](https://onco.cc/drugs/gilteritinib/), [Glasdegib](https://onco.cc/drugs/glasdegib/), [Hydroxyurea (hydroxycarbamide)](https://onco.cc/drugs/hydroxyurea/), [Ivosidenib](https://onco.cc/drugs/ivosidenib/), [Midostaurin](https://onco.cc/drugs/midostaurin/), [Quizartinib](https://onco.cc/drugs/quizartinib/), [Revumenib](https://onco.cc/drugs/revumenib/), [Venetoclax](https://onco.cc/drugs/venetoclax/)
- trials: [AGILE](https://onco.cc/trials/agile/), [myeloMATCH](https://onco.cc/trials/myelomatch/), [VIALE-A](https://onco.cc/trials/viale-a/)
- ideas: [Shorter venetoclax courses in unfit AML](https://onco.cc/ideas/idea-shortened-venetoclax/)
- pairings: [Venetoclax + hypomethylating agent](https://onco.cc/pairings/venetoclax-plus-hma/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/)

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