Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
Brian J Druker, François Guilhot, Stephen G O'Brien, Insa Gathmann, Hagop Kantarjian, Norbert Gattermann, Michael W N Deininger, Richard T Silver, John M Goldman, Richard M Stone, Francisco Cervantes, Andreas Hochhaus, Bayard L Powell, Janice L Gabrilove, Philippe Rousselot, Josy Reiffers, Jan J Cornelissen, Timothy Hughes, Hermine Agis, Thomas Fischer, Gregor Verhoef, John Shepherd, Giuseppe Saglio, Alois Gratwohl, Johan L Nielsen, Jerald P Radich, Bengt Simonsson, Kerry Taylor, Michele Baccarani, Charlene So, Laurie Letvak, Richard A Larson, IRIS Investigators, Brian J Druker, François Guilhot, Stephen G O'Brien, Insa Gathmann, Hagop Kantarjian, Norbert Gattermann, Michael W N Deininger, Richard T Silver, John M Goldman, Richard M Stone, Francisco Cervantes, Andreas Hochhaus, Bayard L Powell, Janice L Gabrilove, Philippe Rousselot, Josy Reiffers, Jan J Cornelissen, Timothy Hughes, Hermine Agis, Thomas Fischer, Gregor Verhoef, John Shepherd, Giuseppe Saglio, Alois Gratwohl, Johan L Nielsen, Jerald P Radich, Bengt Simonsson, Kerry Taylor, Michele Baccarani, Charlene So, Laurie Letvak, Richard A Larson, IRIS Investigators
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].)
Copyright 2006 Massachusetts Medical Society.
Source: PubMed