Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study

• Published in: Blood Vol. 113; no. 19; pp. 4497 - 4504
• Main Authors: Baccarani, Michele, Rosti, Gianantonio, Castagnetti, Fausto, Haznedaroglu, Ibrahim, Porkka, Kimmo, Abruzzese, Elisabetta, Alimena, Giuliana, Ehrencrona, Hans, Hjorth-Hansen, Henrik, Kairisto, Veli, Levato, Luciano, Martinelli, Giovanni, Nagler, Arnon, Lanng Nielsen, Johan, Ozbek, Ugur, Palandri, Francesca, Palmieri, Fausto, Pane, Fabrizio, Rege-Cambrin, Giovanna, Russo, Domenico, Specchia, Giorgina, Testoni, Nicoletta, Weiss-Bjerrum, Ole, Saglio, Giuseppe, Simonsson, Bengt
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 07.05.2009; Americain Society of Hematology
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Benzamides; Biological and medical sciences; Cytogenetic Analysis; Dose-Response Relationship, Drug; Europe; Female; Fusion Proteins, bcr-abl - genetics; Hematologic and hematopoietic diseases; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; MEDICIN; MEDICINE; Middle Aged; Piperazines - administration & dosage; Prognosis; Protein Kinase Inhibitors - administration & dosage; Protein-Tyrosine Kinases - antagonists & inhibitors; Pyrimidines - administration & dosage; Risk Factors; Survival Rate; Treatment Outcome; Young Adult; Europe; Antineoplastic agent; High risk; Imatinib; Hematology; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Chronic myelogenous leukemia; Malignant hemopathy; First line treatment; Myeloproliferative syndrome; Philadelphia-positive leukemia; Protein-tyrosine kinase; Comparative study; Cancer
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2008-12-191254

Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph+ CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P = .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.gov as #NCT00514488.