Blood Journal
Leading the way in experimental and clinical research in hematology

Dasatinib or imatinib in newly diagnosed chronic phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION)

  1. Hagop M Kantarjian1,*,
  2. Neil P Shah2,
  3. Jorge E Cortes1,
  4. Michele Baccarani3,
  5. Mohan B Agarwal4,
  6. María Soledad Undurraga5,
  7. Jianxiang Wang6,
  8. Juan Julio Kassack Ipiña7,
  9. Dong-Wook Kim8,
  10. Michinori Ogura9,
  11. Carolina Pavlovsky10,
  12. Christian Junghanss11,
  13. Jorge H Milone12,
  14. Franck E Nicolini13,
  15. Tadeusz Robak14,
  16. Jan Van Droogenbroeck15,
  17. Edo Vellenga16,
  18. M Brigid Bradley-Garelik17,
  19. Chao Zhu17, and
  20. Andreas Hochhaus18
  1. 1 University of Texas M.D. Anderson Cancer Center, Houston, TX, United States;
  2. 2 University of California, San Francisco School of Medicine, San Francisco, CA, United States;
  3. 3 Department of Hematology-Oncology "L. and A. Seragnoli", University of Bologna, Bologna, Italy;
  4. 4 Institute of Medical Sciences, Bombay Hospital, Mumbai, India;
  5. 5 Department of Hematology, Hospital del Salvador, Santiago, Chile;
  6. 6 Department of Clinical Hematology, Institute of Hematology and Blood Diseases Hospital, Tianjin, China;
  7. 7 Hospital General de Mexico, Mexico City, Mexico;
  8. 8 Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of;
  9. 9 Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan;
  10. 10 FUNDALEU, Angelica Ocampo Hospitalization and Clinical Research Center, Buenos Aires, Argentina;
  11. 11 Department of Hematology/Oncology, University of Rostock, Rostock, Germany;
  12. 12 Department of Hematology, Hospital Italiano de La Plata, Buenos Aires, Argentina;
  13. 13 Hematology Department, Edouard Herriot Hospital, Lyon, France;
  14. 14 Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland;
  15. 15 Department of Haematology, AZ St Jan Hospital, Brugge, Belgium;
  16. 16 Department of Hematology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands;
  17. 17 Bristol-Myers Squibb, Wallingford, CT, United States;
  18. 18 Abteilung Haematologie/Onkologie, Universitaetsklinikum Jena, Jena, Germany
  1. * Corresponding author; email: hkantarj{at}mdanderson.org

Abstract

Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase (CP) CML were randomized to receive dasatinib 100 mg (n=259) or imatinib 400 mg (n=260) once daily. Primary data showed superior efficacy for dasatinib compared with imatinib after 12 months, including significantly higher rates of complete cytogenetic response (CCyR), confirmed CCyR (primary endpoint), and major molecular response (MMR). Here, 24-month data are presented. Cumulative response rates by 24 months in dasatinib and imatinib arms were: CCyR in 86% vs 82%, MMR in 64% vs 46%, and BCR-ABL reduction to ≤0.0032% (4.5-log reduction) in 17% vs 8%. Transformation to accelerated/blast phase CML on study occurred in 2.3% with dasatinib vs 5.0% with imatinib. BCR-ABL mutations, assessed after discontinuation, were detected in 10 patients in each arm. In safety analyses, fluid retention, superficial edema, myalgia, vomiting, and rash were less frequent with dasatinib compared with imatinib, whereas pleural effusion and grade 3/4 thrombocytopenia were more frequent with dasatinib. Overall, dasatinib continues to show faster and deeper responses compared with imatinib, supporting first-line use of dasatinib in patients with newly diagnosed CML-CP. This study was registered at ClinicalTrials.gov: NCT00481247.

  • Submitted August 26, 2011.
  • Accepted November 26, 2011.