# IRIS: imatinib versus interferon plus cytarabine as first treatment for chronic myeloid leukaemia

Source: https://onco.cc/key-papers/paper-iris-imatinib-nejm-2003/  
OnCo record `paper-iris-imatinib-nejm-2003` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Imatinib beat the previous standard by a wide margin in newly diagnosed CML, and the long-term follow-up showed most patients alive at ten years.

## Summary

IRIS randomised 1106 patients with newly diagnosed chronic-phase CML to imatinib 400 mg daily or interferon alfa plus low-dose cytarabine. The primary endpoint was progression-free survival; secondary endpoints included haematological and cytogenetic response. At 18 months the complete cytogenetic response rate was 76.2% with imatinib versus 14.5%, and freedom from progression to accelerated phase or blast crisis was 96.7% versus 91.5%. Crossover from the interferon arm was extensive. The 10-year follow-up (Hochhaus et al., NEJM 2017) reported estimated overall survival of 83.3% on imatinib, with few new serious adverse events after the first year.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2003
- DOI: 10.1056/NEJMoa022457
- Authors: O'Brien SG, Guilhot F, Larson RA, et al.
- Findings: 1106 patients randomised; imatinib 400 mg/day vs interferon alfa + low-dose cytarabine.; Complete cytogenetic response at 18 months: 76.2% vs 14.5%; major cytogenetic response 87.1% vs 34.7%.; Freedom from progression to accelerated phase or blast crisis at 18 months: 96.7% vs 91.5%.; Imatinib was far better tolerated; most interferon patients eventually crossed over.; 10-year follow-up: estimated overall survival 83.3% on imatinib, close to age-matched population survival.
- What it means: IRIS made imatinib the first-line standard for CML worldwide and established the tyrosine kinase inhibitor as a chronic, life-long oral therapy. For most patients CML became a manageable condition with near-normal life expectancy. Later generations of TKIs (dasatinib, nilotinib, asciminib) produce faster, deeper responses but have not shown a survival advantage over imatinib.
- Caveats: Heavy crossover meant overall survival could not be compared cleanly between arms.; The primary endpoint was progression, not survival; molecular response monitoring was introduced later.; Long-term data come from the imatinib arm alone.; Treatment-free remission, now a goal for deep responders, was not part of the original design.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa022457
- 10-year follow-up (Hochhaus 2017): https://doi.org/10.1056/NEJMoa1609324
- ClinicalTrials.gov NCT00006343: https://clinicaltrials.gov/study/NCT00006343

## Connected records

- 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/)
- cancers: [Chronic myeloid leukaemia (CML)](https://onco.cc/cancers/cml/), [Chronic myeloid leukaemia, accelerated and blast phase](https://onco.cc/cancers/cml-advanced-phase/), [Chronic myeloid leukaemia, chronic phase](https://onco.cc/cancers/cml-chronic-phase/)
- targets: [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/targets/bcr-abl/)
- drugs: [Asciminib](https://onco.cc/drugs/asciminib/), [Dasatinib](https://onco.cc/drugs/dasatinib/), [Imatinib](https://onco.cc/drugs/imatinib/), [Nilotinib](https://onco.cc/drugs/nilotinib/)
- companies: [Novartis](https://onco.cc/companies/novartis/)
- terms: [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- bottlenecks: [Most of the world has almost no cancer care](https://onco.cc/bottlenecks/b-global-access/), [Prices and value](https://onco.cc/bottlenecks/b-drug-pricing/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- people: [Timothy P. Hughes](https://onco.cc/people/timothy-hughes/)

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