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Chronic Myeloproliferative Neoplasias

Prediction of outcomes in patients with Ph+ chronic myeloid leukemia in chronic phase treated with nilotinib after imatinib resistance/intolerance

Leukemia volume 27, pages 907–913 (2013)Cite this article

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Abstract

The purpose was to assess predictive factors for outcome in patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP) treated with nilotinib after imatinib failure. Imatinib-resistant and -intolerant patients with CML-CP (n=321) were treated with nilotinib 400 mg twice daily. Of 19 baseline patient and disease characteristics and two response end points analyzed, 10 independent prognostic factors were associated with progression-free survival (PFS). In the multivariate analysis, major cytogenetic response (MCyR) within 12 months, baseline hemoglobin ⩾120 g/l, baseline basophils <4%, and absence of baseline mutations with low sensitivity to nilotinib were associated with PFS. A prognostic score was created to stratify patients into five groups (best group: 0 of 3 unfavorable risk factors and MCyR by 12 months; worst group: 3 of 3 unfavorable risk factors and no MCyR by 12 months). Estimated 24-month PFS rates were 90%, 79%, 67% and 37% for patients with prognostic scores of 0, 1, 2 and 3, respectively, (no patients with score of 4). Even in the presence of poor disease characteristics, nilotinib provided significant clinical benefit in patients with imatinib-resistant or -intolerant CML. This system may yield insight on the prognosis of patients.

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Acknowledgements

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Michael Mandola, PhD for medical editorial assistance with this manuscript.

Authors Contributions

EJ, JEC, FJG, JP-I, OGO, AH, TPH, JPR, D-WK, GM and HMK designed the study; HMK provided administrative support; EJ, PDlC, JC, FJG, JP-I, RAL, NG, OGO, TPH, JPR, D-WK, GM, MB and HMK provided study materials; EJ, PDlC, KNB, NG and AH collected and assembled data; EJ, JEC, AH, GS, D-WK, JR, RCW, MB and HMK analyzed and interpreted data; and all authors drafted/approved the manuscript.

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Authors and Affiliations

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

    E Jabbour, J Cortes & H M Kantarjian

  2. Medizinische Klinik m.S. Hämatologie und Onkologie, Charité—University of Medicine Berlin, Berlin, Germany

    P D le Coutre

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

    F Giles

  4. Kansas University Medical Center, University of Kansas Cancer Center, Kansas City, KS, USA

    K N Bhalla

  5. Malignant Hematology Division, H Lee Moffitt Cancer Center, Tampa, FL, USA

    J Pinilla-Ibarz

  6. University of Chicago, Chicago, IL, USA

    R A Larson

  7. Heinrich-Heine-Universitat, Düsseldorf, Germany

    N Gattermann

  8. Medizinische Klinik II - Johann Wolfgang Goethe-University, Frankfurt, Germany

    O G Ottmann

  9. Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany

    A Hochhaus

  10. Royal Adelaide Hospital, SA Pathology, Adelaide, South Australia, Australia

    T P Hughes

  11. Division of Internal Medicine & Hematology, University of Turin, Orbassano, Italy

    G Saglio

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

    J P Radich

  13. Seoul St Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea

    D-W Kim

  14. Institute of Hematology “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy

    G Martinelli & M Baccarani

  15. Novartis Pharma AG, Basel, Switzerland

    J Reynolds

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

    R C Woodman

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  1. E Jabbour
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  18. M Baccarani
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Corresponding author

Correspondence to E Jabbour.

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Competing interests

EJ received honoraria from Novartis and BMS. PDlC acted as a consultant and received honoraria for Novartis and BMS and received research funding from Novartis. JEC acted as a consultant for Novartis, BMS and Pfizer and received research funding from Novartis, BMS, Pfizer, Ariad and Chemgenex. FJG acted as a consultant, received honoraria and research funding from Novartis. KNB received honoraria and research funding from Novartis. JP-I acted as a consultant for Novartis and BMS and received honoraria from Novartis. RAL acted as a consultant, received honoraria, and received research funding from Novartis. NG received honoraria and research funding from Novartis. OGO acted as a consultant, received honoraria, and research funding from Novartis. AH acted as a consultant for Novartis, BMS, Pfizer and Ariad, and received honoraria and research funding from Novartis, BMS and Pfizer. TPH acted as a consultant and received research funding from Novartis, BMS and Ariad. GS acted as a consultant for Novartis, BMS and Pfizer and received honoraria from BMS and Novartis. JPR acted as a consultant for Novartis, BMS, Ariad and Pfizer and received research funding from Novartis. D-WK received honoraria from Novartis and BMS and received research funding from Novartis, BMS, Pfizer and Ariad. GM acted as a consultant for Novartis, BMS, Pfizer and Genzyme, and received honoraria from Novartis and BMS; and research funding from Novartis. JR and RCW are Novartis employees and stock owners. MB acted as a consultant for Novartis, BMS and Pfizer, and received honoraria from Novartis, BMS and Pfizer, and received research funding from Novartis. HMK acted as a consultant for Novartis and received research funding from Novartis, BMS and Pfizer.

Additional information

Presented in abstract form at the 51st annual meeting of the American Society of Hematology, New Orleans, LA, December 7, 2009.

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Jabbour, E., le Coutre, P., Cortes, J. et al. Prediction of outcomes in patients with Ph+ chronic myeloid leukemia in chronic phase treated with nilotinib after imatinib resistance/intolerance. Leukemia 27, 907–913 (2013). https://doi.org/10.1038/leu.2012.305

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