Advertisement

International Journal of Hematology

, Volume 105, Issue 6, pp 792–804 | Cite as

Dasatinib versus imatinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia: a subanalysis of the DASISION 5-year final report

  • Hirohisa NakamaeEmail author
  • Shin Fujisawa
  • Michinori Ogura
  • Toshiki Uchida
  • Yasushi Onishi
  • Masafumi Taniwaki
  • Atae Utsunomiya
  • Kosei Matsue
  • Yasushi Takamatsu
  • Kensuke Usuki
  • Mitsune Tanimoto
  • Yoji Ishida
  • Kazuteru Ohashi
  • Li Li
  • Masafumi Miyoshi
Original Article

Abstract

The international phase III DASISION trial demonstrated improved efficacy of dasatinib versus imatinib in treatment-naive patients with chronic myeloid leukemia in the chronic phase (CML-CP). We report efficacy and safety outcomes in a Japanese population from the final, 5-year follow-up of DASISION. At the end of the study, 77% (20/26) of dasatinib-treated and 61% (14/23) of imatinib-treated patients remained on initial therapy. Improved responses were observed in Japanese patients who received dasatinib versus imatinib (complete cytogenetic response: 96 vs 87%; major molecular response: 88 vs 74%; BCR-ABL1 ≤0.0032% International Scale [MR4.5]: 58 vs 52%). In patients who achieved BCR-ABL1 ≤10% at 3 months, 5-year progression-free survival and overall survival rates were high with dasatinib (96 and 96%) and imatinib (88 and 100%). The majority of adverse events were grade 1/2 in Japanese patients. Pleural effusion occurred more frequently in dasatinib-treated Japanese patients versus all patients (42 vs 28%), with no treatment discontinuations. Overall, in Japanese patients, dasatinib maintained its safety profile and had higher or comparable response and survival outcomes compared with imatinib or with all patients in DASISION. These findings demonstrate the long-term efficacy and tolerability of dasatinib and support frontline treatment of Japanese patients with CML-CP with dasatinib.

Keywords

CML Tyrosine kinase inhibitor Dasatinib Imatinib Japan 

Notes

Acknowledgements

The authors would like to thank all participating study sites for this Bristol-Myers Squibb (BMS)-sponsored analysis. Professional medical writing and editorial assistance was provided by Kelly M. Fahrbach, PhD, of StemScientific, an Ashfield Company, part of UDG Healthcare plc, funded by BMS. The authors did not receive financial compensation from BMS for authoring this manuscript.

Author contributions

All authors provided feedback and guidance on the analysis and interpretation of the results, critically reviewed and provided revisions to the manuscript, and approved the final draft for submission.

Compliance with ethical standards

Conflict of interest

Hirohisa Nakamae has worked as a consultant for, received honoraria from, received research funding and travel expense reimbursement from, and served on speakers’ bureaus for Bristol-Myers Squibb and Novartis. Shin Fujisawa received research funding from Pfizer. Michinori Ogura has received research funding from Celltrion and SymBio Pharmaceuticals, has received honoraria from AstraZeneca, Janssen, and Takeda, and acted as a consultant for AstraZeneca, Celltrion, Meiji-Seika Pharma, and Mundipharma. Toshiki Uchida has received honoraria from Janssen Pharmaceuticals. Yasushi Onishi has received research funding from Bristol-Myers Squibb KK, and Novartis. Masafumi Taniwaki has received research funding from Chugai Pharmaceutical, Eisai, Kyowa Hakko Kirin, Pfizer, and Toyama Chemical. Atae Utsunomiya has served as a consultant to and received honoraria from Bristol-Myers Squibb KK and Kyowa Kakko Kirin Co., Ltd. Kosei Matsue has received honoraria from Celgene. Yasushi Takamatsu has received honoraria from Celgene, Kyowa Hakko Kirin, and Taisho Toyama Pharmaceutical. Kensuke Usuki has received research funding from Astellas Pharma, Fujimoto Pharmaceutical, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma. Mitsune Tanimoto has received research funding from Astellas Pharma, Chugai Pharmaceutical, Kyowa Hakko Kirin, Nippon Shinyaku, Novartis, Otsuka Pharmaceutical, and Pfizer. Yoji Ishida declares no conflict of interest. Kazuteru Ohashi declares no conflict of interest. Li Li is an employee of Bristol-Myers Squibb. Masafumi Miyoshi is an employee of Bristol-Myers Squibb KK.

References

  1. 1.
    Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17.CrossRefPubMedGoogle Scholar
  2. 2.
    Gleevec® (imatinib) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2015. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/gleevec_tabs.pdf. Accessed 1 Nov 2016.
  3. 3.
    O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004.CrossRefPubMedGoogle Scholar
  4. 4.
    Alvarado Y, Kantarjian H, O’Brien S, Faderl S, Borthakur G, Burger J, et al. Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long-term outcome of patients with early chronic myeloid leukemia in chronic phase. Cancer. 2009;115:3709–18.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Branford S, Kim DW, Soverini S, Haque A, Shou Y, Woodman RC, et al. Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib. J Clin Oncol. 2012;30:4323–9.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Hanfstein B, Müller MC, Hehlmann R, Erben P, Lauseker M, Fabarius A, et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia. 2012;26:2096–102.CrossRefPubMedGoogle Scholar
  7. 7.
    Hughes TP, Hochhaus A, Branford S, Müller MC, Kaeda JS, Foroni L, et al. IRIS investigators. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood. 2010;116(19):3758–65.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Jabbour E, Kantarjian HM, Saglio G, Steegmann JL, Shah NP, Boqué C, 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
  9. 9.
    Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boqué C, et al. Final 5-year study results of DASISION: the dasatinib versus imatinib study in treatment-naive chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34:2333–40.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim DW, Issaragrisil S, 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
  11. 11.
    Sprycel® (dasatinib) [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.; 2015. https://packageinserts.bms.com/pi/pi_sprycel.pdf. Accessed 1 Nov 2016.
  12. 12.
    Kim DW, Banavali SD, Bunworasate U, Goh YT, Ganly P, Huang H, et al. Chronic myeloid leukemia in the Asia-Pacific region: current practice, challenges and opportunities in the targeted therapy era. Leuk Res. 2010;34:1459–71.CrossRefPubMedGoogle Scholar
  13. 13.
    Efficace F, Baccarani M, Breccia M, Alimena G, Rosti G, Cottone F, et al. GIMEMA. Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. Blood. 2011;118:4554–60.CrossRefPubMedGoogle Scholar
  14. 14.
    World Health Organization Union for International Cancer Control. 2014 Review of Cancer Medicines: Chronic Myeloid Leukemia—Executive Summary; 2014. http://www.who.int/selection_medicines/committees/expert/20/applications/CML.pdf?ua=1. Accessed October 10, 2016.
  15. 15.
    Mendizabal AM, Younes N, Levine PH. Geographic and income variations in age at diagnosis and incidence of chronic myeloid leukemia. Int J Hematol. 2016;103:70–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Chuah CT, Nakamae H, Shen ZX, Bradley-Garelik MB, Kim DW. Efficacy and safety of dasatinib versus imatinib in the East Asian subpopulation of the DASISION trial of newly diagnosed chronic myeloid leukemia in chronic phase. Leuk Lymphoma. 2014;55:2093–100.CrossRefPubMedGoogle Scholar
  17. 17.
    Ng KP, Hillmer AM, Chuah CT, Juan WC, Ko TK, Teo AS, et al. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med. 2012;18(4):521–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Ohnishi K, Nakaseko C, Takeuchi J, Fujisawa S, Nagai T, Yamazaki H, et al. Japan Adult Leukemia Study Group. Long-term outcome following imatinib therapy for chronic myelogenous leukemia, with assessment of dosage and blood levels: the JALSG CML202 study. Cancer Sci. 2012;103:1071–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Iriyama N, Fujisawa S, Yoshida C, Wakita H, Chiba S, Okamoto S, et al. Early cytotoxic lymphocyte expansion contributes to a deep molecular response to dasatinib in patients with newly diagnosed chronic myeloid leukemia in the chronic phase: results of the D-first study. Am J Hematol. 2015;90:819–24.CrossRefPubMedGoogle Scholar
  20. 20.
    Fujisawa S, Nakamae H, Ogura M, Ishizawa K, Taniwaki M, Utsunomiya A, et al. Efficacy and safety of dasatinib versus imatinib in Japanese patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP): subset analysis of the DASISION trial with 2-year follow-up. Int J Hematol. 2014;99:141–53.CrossRefPubMedGoogle Scholar
  21. 21.
    Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362:2260–70.CrossRefPubMedGoogle Scholar
  22. 22.
    Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, et al. Writing Committee for the Collaborative CML Prognostic Factors Project Group. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst. 1998;90:850–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol. 2009;27:6041–51.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Gainor JF, Chabner BA. Ponatinib: accelerated disapproval. Oncologist. 2015;20:847–8.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Quintás-Cardama A, Kantarjian H, Cortes J. Nilotinib-associated vascular events. Clin Lymphoma Myeloma Leuk. 2012;12:337–40.CrossRefPubMedGoogle Scholar
  26. 26.
    Saglio G, le Coutre P, Cortes J, Mayer J, Rowlings PA, Mahon F-X, et al. The observed and expected incidence of cardiovascular ischemic events in dasatinib-treated patients across a clinical trial program [abstract]. Blood. 2014;124:4534.Google Scholar

Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  • Hirohisa Nakamae
    • 1
    Email author
  • Shin Fujisawa
    • 2
  • Michinori Ogura
    • 3
    • 4
  • Toshiki Uchida
    • 3
  • Yasushi Onishi
    • 5
  • Masafumi Taniwaki
    • 6
  • Atae Utsunomiya
    • 7
  • Kosei Matsue
    • 8
  • Yasushi Takamatsu
    • 9
  • Kensuke Usuki
    • 10
  • Mitsune Tanimoto
    • 11
  • Yoji Ishida
    • 12
  • Kazuteru Ohashi
    • 13
  • Li Li
    • 14
  • Masafumi Miyoshi
    • 15
  1. 1.Department of Hematology, Graduate School of MedicineOsaka City UniversityOsakaJapan
  2. 2.Department of HematologyYokohama City University Medical CenterYokohamaJapan
  3. 3.Department of Hematology and OncologyJapanese Red Cross Nagoya Daini HospitalNagoyaJapan
  4. 4.Department of HematologyTokai Central HospitalGifuJapan
  5. 5.Department of Hematology and RheumatologyTohoku University HospitalSendaiJapan
  6. 6.Department of Hematology, University HospitalKyoto Prefectural University of MedicineKyotoJapan
  7. 7.Department of HematologyImamura Bun-in HospitalKagoshimaJapan
  8. 8.Department of Internal MedicineKameda Medical CenterChibaJapan
  9. 9.Division of Medical Oncology, Hematology and Infectious Diseases, Department of Internal MedicineFukuoka University HospitalFukuokaJapan
  10. 10.Department of HematologyNTT Medical Center TokyoTokyoJapan
  11. 11.Department of Hematology and OncologyOkayama University HospitalOkayamaJapan
  12. 12.Department of Hematology and Oncology, Internal MedicineIwate Medical University School of MedicineMoriokaJapan
  13. 13.Cancer and Infectious Diseases CenterTokyo Metropolitan Komagome HospitalTokyoJapan
  14. 14.Bristol-Myers SquibbPrincetonUSA
  15. 15.Bristol-Myers SquibbTokyoJapan

Personalised recommendations