Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: Results of a phase 2 study

Moshe Talpaz, Richard T. Silver, Brian J. Druker, John M. Goldman, Carlo Gambacorti-Passerini, Francois Guilhot, Charles A. Schiffer, Thomas Fischer, Michael W.N. Deininger, Anne L. Lennard, Andreas Hochhaus, Oliver G. Ottmann, Alois Gratwohl, Michele Baccarani, Richard Stone, Sante Tura, Francois Xavier Mahon, Sofia Fernandes-Reese, Insa Gathmann, Renaud CapdevilleHagop M. Kantarjian, Charles L. Sawyers

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Abstract

Chronic myelogenous leukemia (CML) is caused by expression of the BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies. Imatinib (formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl kinase. A total of 235 CML patients were enrolled in this study, of whom 181 had a confirmed diagnosis of accelerated phase. Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response, time to progression, survival, and toxicity. Imatinib induced hematologic response in 82% of patients and sustained hematologic responses lasting at least 4 weeks in 69% (complete in 34%). The rate of major cytogenetic response was 24% (complete in 17%). Estimated 12-month progression-free and overall survival rates were 59% and 74%, respectively. Nonhematologic toxicity was usually mild or moderate, and hematologic toxicity was manageable. In comparison to 400 mg, imatinib doses of 600 mg/d led to more cytogenetic responses (28% compared to 16%), longer duration of response (79% compared to 57% at 12 months), time to disease progression (67% compared to 44% at 12 months), and overall survival (78% compared to 65% at 12 months), with no clinically relevant increase in toxicity. Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity.

Original languageEnglish (US)
Pages (from-to)1928-1937
Number of pages10
JournalBlood
Volume99
Issue number6
DOIs
StatePublished - Mar 15 2002

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Talpaz, M., Silver, R. T., Druker, B. J., Goldman, J. M., Gambacorti-Passerini, C., Guilhot, F., Schiffer, C. A., Fischer, T., Deininger, M. W. N., Lennard, A. L., Hochhaus, A., Ottmann, O. G., Gratwohl, A., Baccarani, M., Stone, R., Tura, S., Mahon, F. X., Fernandes-Reese, S., Gathmann, I., ... Sawyers, C. L. (2002). Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: Results of a phase 2 study. Blood, 99(6), 1928-1937. https://doi.org/10.1182/blood.V99.6.1928