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