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Therapy

Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results

Leukemia volume 26, pages 1189–1194 (2012)Cite this article

Abstract

Nilotinib (Tasigna) is a potent and selective BCR-ABL inhibitor approved for use in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CML-CP) and in patients with CML-CP and accelerated phase (CML-AP) who are resistant to or intolerant of imatinib. Patients with CML-AP (N=137) with at least 24 months of follow-up or who discontinued early were evaluated to determine the efficacy and tolerability of nilotinib. The majority (55%) of patients achieved a confirmed hematologic response, and 31% attained a confirmed complete hematologic response on nilotinib treatment. Overall, 32% of patients achieved major cytogenetic responses (MCyR), with most being complete cytogenetic responses. Responses were durable, with 66% of patients maintaining MCyR at 24 months. The estimated overall and progression-free survival rates at 24 months were 70% and 33%, respectively. Grade 3/4 neutropenia and thrombocytopenia were each observed in 42% of patients. Non-hematologic adverse events were mostly mild to moderate; the safety profile of nilotinib has not changed with longer follow-up. In all, 20 (15%) patients remained on study at data cutoff. In summary, nilotinib has a manageable safety profile, and can provide favorable long-term outcomes in the pretreated CML-AP patient population for whom treatment options are limited.

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Acknowledgements

We thank Analysis Group Inc., Boston, MA, USA for conducting and assisting with statistical analyses. JFA is grateful for support from the NIHR Biomedical Research Centre funding scheme. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Daniel Hutta, PhD and Erinn Goldman, PhD for medical editorial assistance with this manuscript. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals, sponsors of this study.

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Authors and Affiliations

  1. Charité - University of Medicine Berlin, Berlin, Germany

    P D le Coutre

  2. HRB Clinical Research Facility, Galway, National University of Ireland Galway and Trinity College Dublin, Dublin, Ireland

    F J Giles

  3. Abt. Hämatologie und Internistische Onkologie Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany

    A Hochhaus

  4. Imperial College School of Medicine, Hammersmith Campus, London, UK

    J F Apperley

  5. Department of Haematology, VU University Medical Center, Amsterdam, The Netherlands

    G J Ossenkoppele

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

    R Blakesley

  7. Novartis Institutes for BioMedical Research, Cambridge, MA, USA

    Y Shou

  8. Novartis Pharma AG, Basel, Switzerland

    N J Gallagher

  9. Department of Hematology-Oncology “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy

    M Baccarani

  10. Leukemia Department, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    J Cortes & H M Kantarjian

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  1. P D le Coutre
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Correspondence to P D le Coutre.

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Competing interests

PDleC received research funding and honoraria from Bristol–Myers Squibb and Novartis, and participated in speakers’ bureaus for Bristol–Myers Squibb and Novartis. FJG acted as a consultant for and received research funding and honoraria from Novartis. AH acted as a consultant for Ariad, Bristol–Myers Squibb and Novartis, received research funding from Bristol–Myers Squibb, Novartis and Pfizer, and received honoraria from and participated on advisory committees for Bristol–Meyers Squibb and Novartis. JFA received research funding from Novartis, received honoraria from Bristol–Myers Squibb, Chemgenex and Novartis, and participated on advisory committees for Ariad, Bristol–Myers Squibb, Chemgenex and Novartis. GJO acted as a consultant for and received research funding from Novartis, and has received honoraria and participated on advisory committees for Bristol–Myers Squibb and Novartis. RB and YS are Novartis employees. NJG is an employee and shareholder of Novartis. MB has received research funding from Novartis and acted as a consultant for, received honoraria from and participated in speakers’ bureaus for Bristol–Myers Squibb and Novartis. JC acted as a consultant for Bristol–Myers Squibb, Chemgenex and Pfizer, and received research funding from Ariad, Bristol–Myers Squibb, Chemgenex, Novartis and Pfizer. HMK acted as a consultant for Novartis, and received research funding from Bristol–Myers Squibb, Novartis and Pfizer.

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le Coutre, P., Giles, F., Hochhaus, A. et al. Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results. Leukemia 26, 1189–1194 (2012). https://doi.org/10.1038/leu.2011.323

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