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 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 Capdeville & 2 others Hagop M. Kantarjian, Charles L. Sawyers

Research output: Contribution to journalArticle

918 Citations (Scopus)

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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Leukemia, Myeloid, Accelerated Phase
Cytogenetics
Toxicity
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Survival
Oncogene Proteins
Protein-Tyrosine Kinases
Reaction Time
Disease-Free Survival
Disease Progression
Imatinib Mesylate
Phosphotransferases
Survival Rate

ASJC Scopus subject areas

  • Hematology

Cite this

Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia : Results of a phase 2 study. / Talpaz, Moshe; Silver, Richard T.; Druker, Brian; Goldman, John M.; Gambacorti-Passerini, Carlo; Guilhot, Francois; Schiffer, Charles A.; Fischer, Thomas; Deininger, Michael W N; Lennard, Anne L.; Hochhaus, Andreas; Ottmann, Oliver G.; Gratwohl, Alois; Baccarani, Michele; Stone, Richard; Tura, Sante; Mahon, Francois Xavier; Fernandes-Reese, Sofia; Gathmann, Insa; Capdeville, Renaud; Kantarjian, Hagop M.; Sawyers, Charles L.

In: Blood, Vol. 99, No. 6, 15.03.2002, p. 1928-1937.

Research output: Contribution to journalArticle

Talpaz, M, Silver, RT, Druker, B, Goldman, JM, Gambacorti-Passerini, C, Guilhot, F, Schiffer, CA, Fischer, T, Deininger, MWN, Lennard, AL, Hochhaus, A, Ottmann, OG, Gratwohl, A, Baccarani, M, Stone, R, Tura, S, Mahon, FX, Fernandes-Reese, S, Gathmann, I, Capdeville, R, Kantarjian, HM & Sawyers, CL 2002, 'Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: Results of a phase 2 study', Blood, vol. 99, no. 6, pp. 1928-1937. https://doi.org/10.1182/blood.V99.6.1928
Talpaz, Moshe ; Silver, Richard T. ; Druker, Brian ; Goldman, John M. ; Gambacorti-Passerini, Carlo ; Guilhot, Francois ; Schiffer, Charles A. ; Fischer, Thomas ; Deininger, Michael W N ; Lennard, Anne L. ; Hochhaus, Andreas ; Ottmann, Oliver G. ; Gratwohl, Alois ; Baccarani, Michele ; Stone, Richard ; Tura, Sante ; Mahon, Francois Xavier ; Fernandes-Reese, Sofia ; Gathmann, Insa ; Capdeville, Renaud ; Kantarjian, Hagop M. ; Sawyers, Charles L. / Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia : Results of a phase 2 study. In: Blood. 2002 ; Vol. 99, No. 6. pp. 1928-1937.
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AU - Talpaz, Moshe

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AU - Goldman, John M.

AU - Gambacorti-Passerini, Carlo

AU - Guilhot, Francois

AU - Schiffer, Charles A.

AU - Fischer, Thomas

AU - Deininger, Michael W N

AU - Lennard, Anne L.

AU - Hochhaus, Andreas

AU - Ottmann, Oliver G.

AU - Gratwohl, Alois

AU - Baccarani, Michele

AU - Stone, Richard

AU - Tura, Sante

AU - Mahon, Francois Xavier

AU - Fernandes-Reese, Sofia

AU - Gathmann, Insa

AU - Capdeville, Renaud

AU - Kantarjian, Hagop M.

AU - Sawyers, Charles L.

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N2 - 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.

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