# Chronic myeloid leukaemia, chronic phase

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

## TL;DR

Chronic-phase chronic myeloid leukaemia is the disease that imatinib turned from fatal into manageable: a daily pill blocks the BCR::ABL1 protein that drives it. Blood tests track the leukaemia gene to a millionth, newer pills such as asciminib (ASC4FIRST) reach deeper responses faster, and patients with years of undetectable disease can try stopping.

## Summary

The Philadelphia chromosome, t(9;22), fuses BCR to ABL1 and produces a constitutively active tyrosine kinase; in chronic phase the marrow overproduces mature granulocytes with fewer than 10 percent blasts (WHO) and the disease is symptomless in half of patients, found on a routine blood count. Response is measured by quantitative PCR for BCR::ABL1 on the International Scale, with ELN milestones of 10 percent or less at three months, 1 percent or less at six months and 0.1 percent or less (major molecular response) at twelve months; failure to reach them prompts kinase domain mutation testing and a switch of drug.

IRIS (2003) randomised 1,106 newly diagnosed patients to imatinib or interferon plus cytarabine: complete cytogenetic response at 18 months in 76 percent versus 14 percent, and at ten years 83 percent of imatinib patients were alive, most without progression. Second-generation inhibitors dasatinib (DASISION), nilotinib (ENESTnd) and bosutinib (BFORE) produce faster and deeper responses without a survival advantage, at the cost of pleural effusions, vascular events and liver toxicity respectively. Asciminib, which binds the myristoyl pocket rather than the ATP site, beat investigator-selected inhibitors in ASC4FIRST (2024): major molecular response at 48 weeks in 67.7 percent against 49.0 percent, and 69.3 percent against 40.2 percent for imatinib, with fewer side effects, earning accelerated approval for newly diagnosed disease in October 2024.

Resistance through kinase domain mutations is handled by switching: ponatinib or asciminib for T315I, and the third-generation olverembatinib in China; allogeneic transplant is reserved for failure of several inhibitors. Treatment-free remission is now a goal: EURO-SKI found about half of patients with at least three years of therapy and a year of deep molecular response stayed in remission two years after stopping. The unsolved problems are the residual stem cell pool that keeps the other half relapsing, cardiovascular toxicity over decades of therapy, and the price and access gap that leaves patients in low-income countries on older drugs or none.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: CML-CP; Chronic-phase CML; Newly diagnosed Ph-positive CML; BCR::ABL1-positive chronic phase
- Tags: subtype-page
- Group: haematologic
- Burden: About 95 percent of people with chronic myeloid leukaemia are diagnosed in chronic phase; on a tyrosine kinase inhibitor their life expectancy is close to that of the general population, and about half of those who reach a deep, stable molecular response can stop treatment.
- Subtypes: Newly diagnosed chronic phase, low ELTS risk; Newly diagnosed chronic phase, high ELTS risk; Chronic phase resistant or intolerant to first tyrosine kinase inhibitor; Chronic phase with T315I mutation (ponatinib, asciminib, olverembatinib); Chronic phase in sustained deep molecular response (treatment-free remission candidate); Chronic phase in pregnancy or in children
- Biomarkers: BCR::ABL1 transcript by quantitative PCR on the International Scale; ELTS and Sokal risk scores; Karyotype and additional chromosomal abnormalities; BCR::ABL1 kinase domain mutations (T315I and others); Depth of molecular response (MR4, MR4.5) for stopping; Cardiovascular risk profile before nilotinib or ponatinib

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/cml-chronic-phase/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/cml-chronic-phase/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/cml-chronic-phase/#what-it-is [6 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/cml-chronic-phase/#finding-it [6 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/cml-chronic-phase/#treating-it [3 settings, 2 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/cml-chronic-phase/#evidence [10 trials, 2 key papers, 8 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/cml-chronic-phase/#science [4 targets, 2 pathways]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/cml-chronic-phase/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/cml-chronic-phase/#living-with-it [16 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/cml-chronic-phase/coming/ [8 medicines, 9 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/cml-chronic-phase/data/ [45 connected records]

## Standard of care

- Newly diagnosed chronic phase: Imatinib 400 mg daily, a second-generation inhibitor (dasatinib, nilotinib, bosutinib) chosen by comorbidity and treatment goal, or asciminib (ASC4FIRST); PCR at 3, 6 and 12 months against ELN milestones. ([Imatinib](https://onco.cc/drugs/imatinib/), [Dasatinib](https://onco.cc/drugs/dasatinib/), [Nilotinib](https://onco.cc/drugs/nilotinib/), [Bosutinib](https://onco.cc/drugs/bosutinib/), [Asciminib](https://onco.cc/drugs/asciminib/), [A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP](https://onco.cc/trials/nct04971226/), [A Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (≥18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)](https://onco.cc/trials/nct05456191/), [Molecular response (MMR, MR4, treatment-free remission)](https://onco.cc/terms/molecular-response/))
- Resistance or intolerance: Switch inhibitor guided by kinase domain mutation testing; ponatinib or asciminib for T315I; radotinib or olverembatinib where approved; allogeneic transplant after failure of two or more inhibitors. ([Ponatinib](https://onco.cc/drugs/ponatinib/), [Asciminib](https://onco.cc/drugs/asciminib/), [Olverembatinib](https://onco.cc/drugs/olverembatinib/), [Radotinib](https://onco.cc/drugs/radotinib/), [Study of Olverembatinib (HQP1351) in Patients With CML-CP](https://onco.cc/trials/nct06423911/), [A Phase 3 Study for the Efficacy and Safety of Radotinib in CP-CML Patients With Failure or Intolerance to Previous TKIs](https://onco.cc/trials/nct03459534/), [Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia](https://onco.cc/trials/nct05384587/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))
- Sustained deep molecular response: Attempt treatment-free remission after at least three to five years of therapy and two years of MR4 or better, with monthly PCR for six months; restart on loss of major molecular response. ([Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Molecular response (MMR, MR4, treatment-free remission)](https://onco.cc/terms/molecular-response/), [Residual disease kinetics (BCR-ABL halving and ctDNA slopes)](https://onco.cc/technologies/mrd-kinetics-models/))

## State of the art

- Life expectancy in chronic-phase CML on tyrosine kinase inhibitors approaches that of the general population.
- Asciminib gives the highest first-line molecular response rates yet reported with the fewest side effects.
- About half of patients who reach a deep, stable response can stop treatment and stay in remission.

## Open problems

- The leukaemic stem cells that survive kinase inhibition and cause relapse after stopping.
- Cardiovascular toxicity over decades on second- and third-generation inhibitors.
- Access to any tyrosine kinase inhibitor, and to PCR monitoring, in low-income countries.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Chronic_myelogenous_leukemia
- Wikipedia: https://en.wikipedia.org/wiki/Chronic_myelogenous_leukemia
- NCCN Guidelines: Chronic Myeloid Leukemia: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1427

## Connected records

- cancers: [Chronic myeloid leukaemia (CML)](https://onco.cc/cancers/cml/), [Chronic myeloid leukaemia, accelerated and blast phase](https://onco.cc/cancers/cml-advanced-phase/), [Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL)](https://onco.cc/cancers/all-paediatric-ph-positive/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/), [Residual disease kinetics (BCR-ABL halving and ctDNA slopes)](https://onco.cc/technologies/mrd-kinetics-models/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ABL1](https://onco.cc/targets/abl1/), [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/targets/bcr-abl/)
- pathways: [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/pathways/bcr-abl1-signalling/), [Chronic myeloid leukaemia (KEGG map)](https://onco.cc/pathways/cml-signalling/)
- terms: [BCR::ABL1 kinase domain mutations (T315I and others)](https://onco.cc/terms/abl1-kinase-domain-mutations/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Molecular response (MMR, MR4, treatment-free remission)](https://onco.cc/terms/molecular-response/), [Philadelphia chromosome (Ph+, BCR::ABL1)](https://onco.cc/terms/philadelphia-chromosome/), [Sokal and ELTS risk scores (chronic myeloid leukaemia)](https://onco.cc/terms/sokal-elts-scores/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/)
- trials: [A Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia (CARDINAL)](https://onco.cc/trials/nct06163430/), [A Phase 3 Study for the Efficacy and Safety of Radotinib in CP-CML Patients With Failure or Intolerance to Previous TKIs](https://onco.cc/trials/nct03459534/), [A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP](https://onco.cc/trials/nct04971226/), [A Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (≥18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)](https://onco.cc/trials/nct05456191/), [Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia](https://onco.cc/trials/nct05384587/), [DASISION](https://onco.cc/trials/dasision/), [Randomized Evaluation of Radotinib Versus Imatinib in Phase III Study for Efficacy With Chinese Patients (RERISE China)](https://onco.cc/trials/nct03722420/), [Study of Olverembatinib (HQP1351) in Patients With CML-CP](https://onco.cc/trials/nct06423911/), [Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia](https://onco.cc/trials/nct04925479/), [Study to Determine the Efficacy and Safety of Asciminib in Pediatric Patients With Ph+ CML-CP](https://onco.cc/trials/nct07354074/)
- key papers: [First imatinib trial: a pill that switched off the enzyme driving chronic myeloid leukaemia](https://onco.cc/key-papers/paper-druker-imatinib-phase1-nejm-2001/), [IRIS: imatinib versus interferon plus cytarabine as first treatment for chronic myeloid leukaemia](https://onco.cc/key-papers/paper-iris-imatinib-nejm-2003/)
- drugs: [Asciminib](https://onco.cc/drugs/asciminib/), [Bosutinib](https://onco.cc/drugs/bosutinib/), [Dasatinib](https://onco.cc/drugs/dasatinib/), [Imatinib](https://onco.cc/drugs/imatinib/), [Nilotinib](https://onco.cc/drugs/nilotinib/), [Olverembatinib](https://onco.cc/drugs/olverembatinib/), [Ponatinib](https://onco.cc/drugs/ponatinib/), [Radotinib](https://onco.cc/drugs/radotinib/)
- biomarkers: [BCR::ABL1 T315I](https://onco.cc/biomarkers/bcr-abl1-t315i/), [BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR)](https://onco.cc/biomarkers/bcr-abl1-transcript/)

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JSON: https://onco.cc/api/v1/entities/cml-chronic-phase.json