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

Michele Baccarani, Brian J. Druker, Susan Branford, Dong Wook Kim, Fabrizio Pane, Lidia Mongay, Manisha Mone, Christine Elke Ortmann, Hagop M. Kantarjian, Jerald P. Radich, Timothy P. Hughes, Jorge E. Cortes, François Guilhot

Research output: Contribution to journalArticle

30 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)616-624
Number of pages9
JournalInternational Journal of Hematology
Issue number5
StatePublished - May 2014



  • Chronic myeloid leukemia
  • Imatinib
  • Phase 3 clinical trial
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Hematology

Cite this