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Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase

Leukemia volume 17, pages 2401–2409 (2003)Cite this article

Abstract

We analyzed molecular responses in 55 newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients enrolled in a phase 3 study (the IRIS trial) comparing imatinib to interferon-alfa plus cytarabine (IFN+AraC). BCR-ABL/BCR% levels were measured by real-time quantitative RT-PCR and were significantly lower for the imatinib-treated patients at all time points up to 18 months, P<0.0001. The median levels for imatinib-treated patients continued to decrease and had not reached a plateau by 24 months. A total of 24 IFN+AraC-treated patients crossed over to imatinib. Once imatinib commenced, the median BCR-ABL/BCR% levels in these patients were not significantly different to those on first-line imatinib for the equivalent number of months. The incidence of progression in imatinib-treated patients, defined by hematologic, cytogenetic or quantitative PCR criteria, was significantly higher in the patients who failed to achieve a 1 log reduction by 3 months or a 2 log reduction by 6 months, P=0.002. A total of 49 patients were screened for BCR-ABL kinase domain mutations. Mutations were detected in two imatinib-treated patients who crossed over from IFN+AraC and both lost their imatinib response. In conclusion, first-line imatinib-treated patients had profound reductions in BCR-ABL/BCR%, which significantly exceeded those of IFN+AraC-treated patients and early measurements were predictive of subsequent response.

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Acknowledgements

We thank Bernadette Miller, Nancy Lerda, Chani Field and Rebecca Lawrence for excellent technical assistance. The study coordinators and laboratory staff of each participating center in particular Sonya Walsh, Rosie Hoyt, Jenny Bourne, Robyn Western, Jenny Muirhead, Patricia Plenge, Fran Porteous, Penny Stavros, Cate O'Kane, Bianca Ryan, Helen Lund, Melinda Higgins, Liz O'Flaherty, Deb Taylor, David McDonald, Mirek Kapuscinski, David Westerman, Robyn Rodwell, Neil Van de Water and Cheryl Hutchins. Susanne Meilenbrock for assistance in establishing the study protocol. This study is supported in part by grants from Novartis Pharmaceuticals, Australia.

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Authors and Affiliations

  1. Institute of Medical and Veterinary Science, Adelaide, South Australia

    S Branford, Z Rudzki, A Harper & T P Hughes

  2. Royal Melbourne Hospital, Victoria, Australia

    A Grigg

  3. Mater Hospital, Queensland, Australia

    K Taylor

  4. Royal Brisbane Hospital, Queensland, Australia

    S Durrant

  5. Royal North Shore Hospital, New South Wales, Australia

    C Arthur

  6. Auckland Hospital, New Zealand

    P Browett

  7. The Alfred Hospital, Victoria, Australia

    A P Schwarer

  8. St Vincent's Hospital, New South Wales, Australia

    D Ma

  9. Peter MacCallum Cancer Institute, Victoria, Australia

    J F Seymour

  10. Westmead Hospital, New South Wales, Australia

    K Bradstock

  11. Sir Charles Gairdner Hospital, Western Australia

    D Joske

  12. Novartis Pharmaceuticals Australia, North Ryde, Sydney, Australia

    K Lynch

  13. Novartis Pharma AG, Basel, Switzerland

    I Gathmann

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Branford, S., Rudzki, Z., Harper, A. et al. Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Leukemia 17, 2401–2409 (2003). https://doi.org/10.1038/sj.leu.2403158

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