Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase

Hagop M. Kantarjian, Richard A. Larson, Francois Guilhot, Stephen G. O'Brien, Manisha Mone, Marc Rudoltz, Tillmann Krahnke, Jorge Cortes, Brian J. Druker

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

BACKGROUND: Imatinib mesylate given orally at a daily dose of 400 mg is the standard of care as initial therapy for patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP). Treatment guidelines propose dose escalation based on clinical assessments of disease response. METHODS: Response and survival were analyzed in a cohort of patients (n = 106) with newly diagnosed CML-CP who were enrolled on the International Randomized Study of Interferon and STI571 (IRIS) trial, who began treatment with imatinib at a dose of 400 mg daily, and who subsequently underwent dose escalation to either 600 mg or 800 mg daily. Reasons for dose escalation were evaluated retrospectively based on 2 sets of criteria: the IRIS protocol-defined criteria (n = 39 patients) and the European LeukemiaNet (ELN) recommendations (n = 48 patients). RESULTS: Among all 106 patients who underwent dose escalation, the rates of freedom from progression to accelerated phase or blast phase and overall survival were 89% and 84% at 3 years after dose increase, respectively. A cytogenetic response was obtained in 42% of patients who had their dose escalated based on protocol criteria and in 38% of patients who had their dose escalated according to the ELN recommendations. CONCLUSIONS: The results from this retrospective analysis supported imatinib dose escalation as an appropriate initial option for patients with CML-CP who were experiencing suboptimal cytogenetic response or resistance.

Original languageEnglish (US)
Pages (from-to)551-560
Number of pages10
JournalCancer
Volume115
Issue number3
DOIs
StatePublished - Feb 1 2009

Keywords

  • Chronic myeloid leukemia in chronic phase
  • Dose escalation
  • Imatinib
  • Suboptimal response

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kantarjian, H. M., Larson, R. A., Guilhot, F., O'Brien, S. G., Mone, M., Rudoltz, M., Krahnke, T., Cortes, J., & Druker, B. J. (2009). Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase. Cancer, 115(3), 551-560. https://doi.org/10.1002/cncr.24066