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Comparison of the clinical outcomes of nilotinib and dasatinib therapies in newly diagnosed patients in the chronic phase of chronic myeloid leukemia: a retrospective analysis

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Abstract

Treatment with a tyrosine kinase inhibitor (TKI) is the standard of care for patients with chronic myeloid leukemia (CML). The new-generation TKIs, nilotinib and dasatinib, are found to have deeper and faster treatment response rates compared to imatinib in the first-line setting. However, a direct comparison between nilotinib and dasatinib has never been reported previously. Our study aims to compare the outcomes and molecular responses achieved following the first-line use of these two agents in patients with CML-CP. The database of the CML Cooperative Study Group was reviewed and patients with CML in the chronic phase (CP) who were given nilotinib or dasatinib as first-line therapy were identified. Out of 361 patients with CML-CP enrolled in our database, 58 and 63 had been treated with conventional doses of nilotinib (300 mg twice daily) and dasatinib (100 mg once daily), respectively, as first-line therapy. The patient demographics did not show significant differences between the groups. The event-free survival rates did not differ between these two groups. The major molecular response (MMR) and the deep molecular response (DMR) rates by 6, 12, 18, and 24 months did not differ between groups. Among the three scoring systems, only the Hasford score could predict the achievement of DMR, and all of them failed to predict the achievement of MMR in the entire cohort. Our data suggest that both nilotinib and dasatinib have comparable efficacies and promising outcomes.

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References

  1. Hochhaus A, Larson RA, Guilhot F, et al. Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. N Engl J Med. 2017;376:917–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tauchi T, Kizaki M, Okamoto S, et al. Seven-year follow-up of patients receiving imatinib for the treatment of newly diagnosed chronic myelogenous leukemia by the TARGET system. Leuk Res. 2011;35:585–90.

    Article  CAS  PubMed  Google Scholar 

  3. Giles FJ, le Coutre PD, 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. 2013;27:107–12.

    Article  CAS  PubMed  Google Scholar 

  4. Shah NP, Rousselot P, Schiffer C, et al. Dasatinib in imatinib-resistant or -intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034. Am J Hematol. 2016;91:869–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kantarjian HM, Cortes JE, Kim DW, et al. Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. Blood. 2014;123:1309–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018;132:393–404.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hochhaus A, Saglio G, Hughes TP, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016;30:1044–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-year study results of DASISION: the dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34:2333–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol. 2018;36:231–7.

    Article  PubMed  Google Scholar 

  10. Lipton JH, Chuah C, Guerci-Bresler A, et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17:612–21.

    Article  CAS  PubMed  Google Scholar 

  11. Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122:872–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hughes TP, Saglio G, Kantarjian HM, et al. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. Blood. 2014;123:1353–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jabbour E, Kantarjian HM, Saglio G, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014;123:494–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Iriyama N, Hatta Y, Kobayashi S, et al. The European Treatment and Outcome Study score is associated with clinical outcomes and treatment response following European LeukemiaNet 2013 recommendations in chronic-phase chronic myeloid leukemia. Int J Hematol. 2014;100:379–85.

    Article  PubMed  Google Scholar 

  15. Bonifacio M, Binotto G, Calistri E, et al. EUTOS score predicts early optimal response to imatinib according to the revised 2013 ELN recommendations. Ann Hematol. 2014;93:163–4.

    Article  PubMed  Google Scholar 

  16. Yamamoto E, Fujisawa S, Hagihara M, et al. European Treatment and Outcome Study score does not predict imatinib treatment response and outcome in chronic myeloid leukemia patients. Cancer Sci. 2014;105:105–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Dybko J, Jaźwiec B, Haus O, et al. The hasford score may predict molecular response in chronic myeloid leukemia patients: a single institution experience. Dis Mark. 2016;2016:7531472.

    Google Scholar 

  18. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.

    Article  CAS  Google Scholar 

  19. Cortes JE, Jones D, O’Brien S, et al. Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase. J Clin Oncol. 2010;28:392–7.

    Article  CAS  PubMed  Google Scholar 

  20. Cortes JE, Jones D, O’Brien S, et al. Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. J Clin Oncol. 2010;28:398–404.

    Article  CAS  PubMed  Google Scholar 

  21. Sato E, Iriyama N, Tokuhira M, et al. Introduction of second-generation tyrosine kinase inhibitors may reduce the prognostic impact of high-risk patients, according to the European treatment and outcome study (EUTOS) score. Leuk Lymphoma. 2018;59:1105–12.

    Article  CAS  PubMed  Google Scholar 

  22. Rea D, Mahon FX. How I manage relapse of chronic myeloid leukaemia after stopping tyrosine kinase inhibitor therapy. Br J Haematol. 2018;180:24–32.

    Article  CAS  PubMed  Google Scholar 

  23. Rea D, Ame S, Berger M, et al. Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: recommendations for clinical practice from the French Chronic Myeloid Leukemia Study Group. Cancer. 2018;124:2956–63.

    Article  PubMed  Google Scholar 

  24. Iriyama N, Fujisawa S, Yoshida C, et al. Shorter halving time of BCR-ABL1 transcripts is a novel predictor for achievement of molecular responses in newly diagnosed chronic-phase chronic myeloid leukemia treated with dasatinib: results of the D-first study of Kanto CML study group. Am J Hematol. 2015;90:282–7.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan

    Noriyoshi Iriyama & Yoshihiro Hatta

  2. Department of Hematology, Juntendo University Urayasu Hospital, Urayasu, Japan

    Kei-Ji Sugimoto

  3. Department of Hematology, Juntendo University Nerima Hospital, Tokyo, Japan

    Eriko Sato

  4. Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan

    Tomoiku Takaku, Isao Fujioka & Norio Komatsu

  5. Departments of Hematology, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    Michihide Tokuhira, Yuta Kimura & Masahiro Kizaki

  6. Department of Hematology, Yokohama Municipal Citizen’s Hospital, Yokohama, Japan

    Tomonori Nakazato

  7. Department of Hemato-Oncology, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan

    Maho Ishikawa & Norio Asou

  8. Department of Hematology, Saiseikai Yokohama Nanbu Hospital, Yokohama, Japan

    Hiroyuki Fujita

  9. Department of Medical Technology, Kumamoto Health Science University, Kumamoto, Japan

    Tatsuya Kawaguchi

Authors
  1. Noriyoshi Iriyama
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  2. Kei-Ji Sugimoto
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  3. Eriko Sato
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  4. Tomoiku Takaku
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  5. Michihide Tokuhira
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  6. Tomonori Nakazato
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  7. Maho Ishikawa
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  8. Hiroyuki Fujita
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  9. Isao Fujioka
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  10. Yuta Kimura
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  11. Norio Asou
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  12. Masahiro Kizaki
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  13. Norio Komatsu
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  14. Yoshihiro Hatta
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  15. Tatsuya Kawaguchi
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Corresponding author

Correspondence to Noriyoshi Iriyama.

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Conflict of interest

NI received honoraria and speaker fees from Bristol-Myers Squibb, Novartis Pharma K.K., Otsuka Pharmaceutical, and Pfizer Inc. MT received honoraria and speaker fees from Pfizer Inc. and Bristol-Myers Squibb. MK received honoraria and speaker fees from Bristol-Myers Squibb and Novartis Pharma K.K. TT, and YH received honoraria from Bristol-Myers Squibb and Novartis Pharma K.K. TK received honoraria and speaker fees from Bristol-Myers Squibb, Novartis Pharma K.K., and Pfizer Inc. The remaining authors declare no competing financial interests. All authors have no non-financial conflicts of interest to declare.

Ethical approval

All procedures performed in studies were in accordance with the ethical standards of each institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent was not required due to retrospective fashion of this study.

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Iriyama, N., Sugimoto, KJ., Sato, E. et al. Comparison of the clinical outcomes of nilotinib and dasatinib therapies in newly diagnosed patients in the chronic phase of chronic myeloid leukemia: a retrospective analysis. Med Oncol 35, 142 (2018). https://doi.org/10.1007/s12032-018-1203-7

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  • DOI: https://doi.org/10.1007/s12032-018-1203-7

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