TY - JOUR
T1 - Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia
T2 - Results of a phase 2 study
AU - Talpaz, Moshe
AU - Silver, Richard T.
AU - Druker, Brian J.
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.
PY - 2002/3/15
Y1 - 2002/3/15
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.
AB - 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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U2 - 10.1182/blood.V99.6.1928
DO - 10.1182/blood.V99.6.1928
M3 - Article
C2 - 11877262
AN - SCOPUS:0037085785
SN - 0006-4971
VL - 99
SP - 1928
EP - 1937
JO - Blood
JF - Blood
IS - 6
ER -