Sustained remissions and low rate of BCR-ABL resistance mutations with imatinib treatment chronic myelogenous leukemia in patients treated in late chronic phase: a 5-year follow up.

The introduction of Imatinib (IM) has significantly altered the treatment for CML, although only limited follow-up results are available. As failure of Interferon-alpha had been associated with poor prognosis and results of IM-treatment in this patient group may allow earlier estimation of long-term benefits for early chronic phase patients. Therefore we prospectively analyzed the quality and duration of remissions and the rate of BCR-ABL resistance mutations occurring in patients treated with IM, if they were intolerant or refractory to interferon. Fifty-nine patients were included and median follow up is 4.75 years. Haematologic remission rate was 92% and 62% of patients achieved at least major cytogenetic remission. There were no major differences between patients failing or being refractory to IFN. Major molecular response was observed in 67% of patients evaluable. For the entire group, median PFS was 4.3 years and OS was 82% at 4.75 years. Haematologic and complete cytogenetic remissions, but not molecular responses were correlated with improved PFS and OS. In patients with progression or inadequate response, BCR-ABL kinase domain mutations were detected in 3/28 patients. IM resulted in prolonged remission rates in a substantial proportion after IFN-failure/intolerance, with no differences in these patient groups. Quality of hematologic and cytogenetic, but not molecular response was associated with duration of remissions and survival. A low rate of resistance-mutations was detected, suggesting that alternative mechanism may play an important role in disease progression. (c) 2007 Wiley-Liss, Inc.