Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants
Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IMA) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IMA after IFN-failure (n=128). Primary goals were the comparative response and long-term survival analyses of the experimental arms vs IMA 400 mg.
Patients (aged 16-88y) were recruited by 210 centers in Germany, Switzerland, and the Czech Republic. From July 2002 to March 2012, 1551 newly diagnosed CML patients in chronic phase were randomized, 1536 were evaluable. Molecular monitoring of all patients was an integral part of the study from the beginning.
After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IMA 400 mg and any experimental treatment arm was not different. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IMA 400 mg provides a close to normal life expectancy independent of the time to response. The authors concluded that survival with CML is currently more determined by patients’ and disease factors than by initial treatment selection.
This study provided long term outcome data for adult CML patients on long term treatment with imatinib. However, pediatric CML patients were started on treatment at a much younger age compared to this cohort and may need to continue on treatment for a much longer time, therefore this data cannot directly apply to our patients. If the study can have subgroup analysis of the younger adult patients and their long term outcome in next 2 decades, that may be more meaningful for applying our patients.