Insights from pre-clinical studies for new combination treatment regimens with the Bcr-Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec) in chronic myelogenous leukemia

A translational perspective

P. La Rosée, M. E. O'Dwyer, Brian Druker

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Clinical phase I/II studies with the Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec, formerly STI571) for the treatment for chronic myelogenous leukemia (CML) demonstrated the safety and the remarkable efficacy of this molecularly targeted agent. However, a significant proportion of patients treated in the chronic phase of the disease after having failed interferon alpha (IFN) remain predominantly Philadelphia chromosome positive (Ph+), suggesting a risk of later relapses. Furthermore, results in blast crisis patients revealed a high frequency of relapses or resistance to imatinib. To circumvent resistance, improve response rates, or prolong survival, pre-clinical evaluations of combinations of imatinib with other agents have been pursued. Some of these have already been translated into clinical studies. Here, we first summarize evidence from pre-clinical studies on new combination regimens with imatinib in the treatment of CML. Second, we analyze preliminary clinical data of ongoing combination studies. Finally, we provide a summary of approaches that use novel antileukemic agents with molecularly characterized modes of action.

Original languageEnglish (US)
Pages (from-to)1213-1219
Number of pages7
JournalLeukemia
Volume16
Issue number7
DOIs
StatePublished - 2002

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Phosphotransferases
Therapeutics
Blast Crisis
Recurrence
Philadelphia Chromosome
Imatinib Mesylate
Clinical Studies
Interferon-alpha
Chronic Disease
Safety
Survival

Keywords

  • CML
  • Combination therapy
  • Imatinib mesylate
  • ST1571

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

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title = "Insights from pre-clinical studies for new combination treatment regimens with the Bcr-Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec) in chronic myelogenous leukemia: A translational perspective",
abstract = "Clinical phase I/II studies with the Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec, formerly STI571) for the treatment for chronic myelogenous leukemia (CML) demonstrated the safety and the remarkable efficacy of this molecularly targeted agent. However, a significant proportion of patients treated in the chronic phase of the disease after having failed interferon alpha (IFN) remain predominantly Philadelphia chromosome positive (Ph+), suggesting a risk of later relapses. Furthermore, results in blast crisis patients revealed a high frequency of relapses or resistance to imatinib. To circumvent resistance, improve response rates, or prolong survival, pre-clinical evaluations of combinations of imatinib with other agents have been pursued. Some of these have already been translated into clinical studies. Here, we first summarize evidence from pre-clinical studies on new combination regimens with imatinib in the treatment of CML. Second, we analyze preliminary clinical data of ongoing combination studies. Finally, we provide a summary of approaches that use novel antileukemic agents with molecularly characterized modes of action.",
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AU - O'Dwyer, M. E.

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