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Chronic Myeloproliferative Neoplasias

Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study

Leukemia volume 27, pages 107–112 (2013)Cite this article

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Abstract

Nilotinib (Tasigna) is a BCR–ABL1 tyrosine kinase inhibitor approved for the treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) who are newly diagnosed or intolerant of or resistant to imatinib. The 48-month follow-up data for patients with CML-CP treated with nilotinib after imatinib resistance or intolerance on an international phase II study were analyzed. Overall, 59% of patients achieved major cytogenetic response; 45% achieved complete cytogenetic response while on study. The estimated rate of overall survival (OS) and progression-free survival (PFS) at 48 months was 78% and 57%, respectively. Deeper levels of molecular responses at 3 and 6 months were highly positively correlated with long-term outcomes, including PFS and OS at 48 months. Of the 321 patients initially enrolled in the study, 98 (31%) were treated for at least 48 months. Discontinuations were primarily due to disease progression (30%) or adverse events (21%). Nilotinib is safe and effective for long-term use in responding patients with CML-CP who are intolerant of or resistant to imatinib. Further significant improvements in therapy are required for patients who are resistant or intolerant to imatinib.

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Acknowledgements

We thank Susan Branford, Philipp Erben, Neil Gallagher, Ariful Haque, Martin Müller and Simona Soverini for their contributions. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Cornel Phillip and Erinn Goldman for medical editorial assistance with this manuscript. The research work of Francis Giles, Philipp D le Coutre, Javier Pinilla-Ibarz, Richard A Larson, Norbert Gattermann, Oliver G Ottmann, Andreas Hochhaus, Jerald P Radich, Giuseppe Saglio, Timothy P Hughes, Giovanni Martinelli, Dong-Wook Kim, Jorge Cortes, Michele Baccarani and Hagop M Kantarjian was funded by Novartis Pharma.

Author Contributions

Conception and design: Francis Giles, Philipp D le Coutre, Javier Pinilla-Ibarz, Richard A Larson, Norbert Gattermann, Oliver G Ottmann, Andreas Hochhaus, Jerald P Radich, Giuseppe Saglio, Timothy P Hughes, Giovanni Martinelli, Dong-Wook Kim, Jorge Cortes, Michele Baccarani and Hagop M Kantarjian. Collection and assembly of data: all authors. Manuscript writing: all authors. Final approval of manuscript: all authors. Provision of study materials or patients: Francis Giles, Philipp D le Coutre, Javier Pinilla-Ibarz, Richard A Larson, Norbert Gattermann, Oliver G Ottmann, Andreas Hochhaus, Jerald P Radich, Giuseppe Saglio, Timothy P Hughes, Giovanni Martinelli, Dong-Wook Kim, Jorge Cortes, Michele Baccarani and Hagop M Kantarjian.

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Authors and Affiliations

  1. HRB Clinical Research Facilities, National University of Ireland Galway and Trinity College, Dublin, Ireland

    F J Giles

  2. Department of Hematology and Oncology, Charité-Humboldt-Universität, Campus Virchow Klinikum, Berlin, Germany

    P D le Coutre

  3. H Lee Moffitt Cancer Center, University of South Florida, Tampa, FL, USA

    J Pinilla-Ibarz

  4. University of Chicago, Chicago, IL, USA

    R A Larson

  5. Department of Haematology, Oncology and Clinical Immunology, Heinrich-Heine-Universität, Düsseldorf, Germany

    N Gattermann

  6. Department of Medicine, Hematology/Oncology, University Hospital of Frankfurt, Frankfurt, Germany

    O G Ottmann

  7. Department of Hematology and Oncology, Universitätsklinikum Jena, Jena, Germany

    A Hochhaus

  8. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    J P Radich

  9. Department of Cellular Biotechnologies and Hematology, University at Orbassano, Turin, Italy

    G Saglio

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

    T P Hughes

  11. Department of Hematology/Oncology L and A Seragnoli, University of Bologna, Bologna, Italy

    G Martinelli & M Baccarani

  12. Seoul St Mary’s Hospital, Seoul, Korea

    D-W Kim

  13. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    S Novick, K Gillis & X Fan

  14. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    J Cortes & H M Kantarjian

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  1. F J Giles
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Correspondence to F J Giles.

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Competing interests

Steven Novick, Kathryn Gillis and Xiaolin Fan are either employed or hold a leadership position in Novartis Pharma. The remaining authors declare no conflict of interest.

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Giles, F., le Coutre, P., Pinilla-Ibarz, J. et al. Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study. Leukemia 27, 107–112 (2013). https://doi.org/10.1038/leu.2012.181

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