Advertisement

Medical Oncology

, 35:142 | Cite as

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

  • Noriyoshi Iriyama
  • Kei-Ji Sugimoto
  • Eriko Sato
  • Tomoiku Takaku
  • Michihide Tokuhira
  • Tomonori Nakazato
  • Maho Ishikawa
  • Hiroyuki Fujita
  • Isao Fujioka
  • Yuta Kimura
  • Norio Asou
  • Masahiro Kizaki
  • Norio Komatsu
  • Yoshihiro Hatta
  • Tatsuya Kawaguchi
Original Paper

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.

Keywords

Chronic myeloid leukemia Nilotinib Dasatinib Molecular response Scoring system 

Notes

Compliance with ethical standards

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.

References

  1. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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. 18.
    Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.CrossRefGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Noriyoshi Iriyama
    • 1
  • Kei-Ji Sugimoto
    • 2
  • Eriko Sato
    • 3
  • Tomoiku Takaku
    • 4
  • Michihide Tokuhira
    • 5
  • Tomonori Nakazato
    • 6
  • Maho Ishikawa
    • 7
  • Hiroyuki Fujita
    • 8
  • Isao Fujioka
    • 4
  • Yuta Kimura
    • 5
  • Norio Asou
    • 7
  • Masahiro Kizaki
    • 5
  • Norio Komatsu
    • 4
  • Yoshihiro Hatta
    • 1
  • Tatsuya Kawaguchi
    • 9
  1. 1.Division of Hematology and Rheumatology, Department of MedicineNihon University School of MedicineTokyoJapan
  2. 2.Department of HematologyJuntendo University Urayasu HospitalUrayasuJapan
  3. 3.Department of HematologyJuntendo University Nerima HospitalTokyoJapan
  4. 4.Department of HematologyJuntendo University School of MedicineTokyoJapan
  5. 5.Departments of Hematology, Saitama Medical CenterSaitama Medical UniversitySaitamaJapan
  6. 6.Department of HematologyYokohama Municipal Citizen’s HospitalYokohamaJapan
  7. 7.Department of Hemato-Oncology, Comprehensive Cancer CenterSaitama Medical University International Medical CenterSaitamaJapan
  8. 8.Department of HematologySaiseikai Yokohama Nanbu HospitalYokohamaJapan
  9. 9.Department of Medical TechnologyKumamoto Health Science UniversityKumamotoJapan

Personalised recommendations