International Journal of Hematology

, Volume 99, Issue 5, pp 616–624

Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study


    • Department of Hematology and Oncology “L. e A. Seràgnoli,” S.Orsola-Malpighi University HospitalUniversity of Bologna
  • Brian J. Druker
    • Knight Cancer InstituteOregon Health & Science University
  • Susan Branford
    • Centre for Cancer Biology, SA PathologyUniversity of Adelaide
  • Dong-Wook Kim
    • Seoul St. Mary’s HospitalThe Catholic University of Korea
  • Fabrizio Pane
    • University of Naples Federico II
  • Lidia Mongay
    • Novartis Pharmaceuticals Corporation
  • Manisha Mone
    • Novartis Pharmaceuticals Corporation
  • Christine-Elke Ortmann
    • Novartis Pharma AG
  • Hagop M. Kantarjian
    • The University of Texas, MD Anderson Cancer Center
  • Jerald P. Radich
    • Fred Hutchinson Cancer Research Center
  • Timothy P. Hughes
    • Division of Haematology and Centre for Cancer Biology, SA Pathology, South Australian Health and Medical Research InstituteUniversity of Adelaide
  • Jorge E. Cortes
    • The University of Texas, MD Anderson Cancer Center
  • François Guilhot
    • Inserm CIC 1402
  • On behalf of the TOPS investigators
Original Article

DOI: 10.1007/s12185-014-1566-2

Cite this article as:
Baccarani, M., Druker, B.J., Branford, S. et al. Int J Hematol (2014) 99: 616. doi:10.1007/s12185-014-1566-2


The TOPS trial evaluated high- (800 mg/day; n = 319) versus standard-dose (400 mg/day; n = 157) imatinib in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Patients had a minimum follow-up of 42 months or discontinued early. Major molecular response (MMR) rates were similar between arms at (51.6 vs 50.2 % for 400 and 800 mg/day, respectively; P = 0.77) and by (75.8 vs 79.0 %; P = 0.4807) 42 months. There were no differences in event-free survival (EFS), progression-free survival (PFS), or overall survival (OS) between arms. The estimated rates of PFS on treatment and OS at 42 months were significantly higher in patients with MMR at 6, 12, and 18 months compared with those without MMR. Adverse events were more frequent with high-dose imatinib. Patients with ≤1 treatment interruption (vs >1) and those able to maintain imatinib ≥600 mg/day (vs <600 mg/day) in the first year of treatment had faster and higher response rates, but no improvement in EFS or PFS. Adherence to prescribed dose without interruption may be more important than initiation of therapy with higher doses of imatinib. Achievement of MMR correlated with long-term clinical outcomes.


ImatinibChronic myeloid leukemiaPhase 3 clinical trialBCR-ABLTyrosine kinase inhibitor

Copyright information

© The Japanese Society of Hematology 2014