{"entity":{"id":"paper-iris-imatinib-nejm-2003","kind":"paper","name":"IRIS: imatinib versus interferon plus cytarabine as first treatment for chronic myeloid leukaemia","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa022457"},{"label":"10-year follow-up (Hochhaus 2017)","url":"https://doi.org/10.1056/NEJMoa1609324"},{"label":"ClinicalTrials.gov NCT00006343","url":"https://clinicaltrials.gov/study/NCT00006343"}],"tags":[],"related":["paper-druker-imatinib-phase1-nejm-2001"],"cancers":["cml"],"sections":[],"technologies":[],"targets":["bcr-abl"],"drugs":["imatinib","dasatinib","nilotinib","asciminib"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["pfs","os"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2003,"doi":"10.1056/NEJMoa022457","authors":"O'Brien SG, Guilhot F, Larson RA, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":1106},"route":"/key-papers/paper-iris-imatinib-nejm-2003/","neighbours":{"paper":[{"id":"paper-druker-imatinib-phase1-nejm-2001","kind":"paper","name":"First imatinib trial: a pill that switched off the enzyme driving chronic myeloid leukaemia","route":"/key-papers/paper-druker-imatinib-phase1-nejm-2001/"}],"cancer":[{"id":"cml","kind":"cancer","name":"Chronic myeloid leukaemia (CML)","route":"/cancers/cml/"},{"id":"cml-advanced-phase","kind":"cancer","name":"Chronic myeloid leukaemia, accelerated and blast phase","route":"/cancers/cml-advanced-phase/"},{"id":"cml-chronic-phase","kind":"cancer","name":"Chronic myeloid leukaemia, chronic phase","route":"/cancers/cml-chronic-phase/"}],"target":[{"id":"bcr-abl","kind":"target","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/targets/bcr-abl/"}],"drug":[{"id":"asciminib","kind":"drug","name":"Asciminib","route":"/drugs/asciminib/"},{"id":"dasatinib","kind":"drug","name":"Dasatinib","route":"/drugs/dasatinib/"},{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"nilotinib","kind":"drug","name":"Nilotinib","route":"/drugs/nilotinib/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"term":[{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"bottleneck":[{"id":"b-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/"},{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"person":[{"id":"timothy-hughes","kind":"person","name":"Timothy P. Hughes","route":"/people/timothy-hughes/"}]}}