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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

Leukemia volume 16, pages 1213–1219 (2002)Cite this article

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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Acknowledgements

PL is the recipient of a postdoctoral grant of the Deutsche Krebshilfe, Dr Mildred Scheel Stiftung, Germany. BJD is funded by grants from the NCI, a Specialized Center of Research Award from The Leukemia and Lymphoma Society, a Clinical Scientist Award from the Burroughs Wellcome Fund and the TJ Martell Foundation. BJD is consultant for Novartis Pharmaceuticals Inc. MEO is on the Speakers Bureau of Novartis Pharmaceuticals Inc., and Cell Therapeutics Inc.

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    P La Rosée, ME O'Dwyer & BJ Druker

  2. III Medizinische Universitätsklink, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany

    P La Rosée

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La Rosée, P., O'Dwyer, M. & Druker, B. 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. Leukemia 16, 1213–1219 (2002). https://doi.org/10.1038/sj.leu.2402555

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