Author:

Keywords:

Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Cytarabine, Disease-Free Survival, Female, Follow-Up Studies, Fusion Proteins, bcr-abl, Humans, Interferon-alpha, Kaplan-Meiers Estimate, Leukemia, Myeloid, Chronic, Male, Piperazines, Protein-Tyrosine Kinases, Pyrimidines, Survival Analysis, Survival Rate, Treatment Outcome, Science & Technology, Life Sciences & Biomedicine, Medicine, General & Internal, General & Internal Medicine, CHRONIC MYELOGENOUS LEUKEMIA, ABL TYROSINE KINASE, COMPLETE CYTOGENETIC REMISSION, ALPHA PLUS CYTARABINE, INTERFERON-ALPHA, CHRONIC-PHASE, BLAST CRISIS, CHROMOSOME, RESPONSES, CELLS, Benzamides, Imatinib Mesylate, Kaplan-Meier Estimate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, IRIS Investigators, 11 Medical and Health Sciences, 32 Biomedical and clinical sciences, 42 Health sciences

Abstract:

BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P< /0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events. CONCLUSIONS: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)