Tolerability-Adapted Imatinib 800 mg/d Versus 400 mg/d Versus 400 mg/d Plus Interferon-α in Newly Diagnosed Chronic Myeloid Leukemia

• Published in: Journal of clinical oncology Vol. 29; no. 12; pp. 1634 - 1642
• Main Authors: Hehlmann, Rüdiger, Lauseker, Michael, Jung-Munkwitz, Susanne, Leitner, Armin, Müller, Martin C., Pletsch, Nadine, Proetel, Ulrike, Haferlach, Claudia, Schlegelberger, Brigitte, Balleisen, Leopold, Hänel, Mathias, Pfirrmann, Markus, Krause, Stefan W., Nerl, Christoph, Pralle, Hans, Gratwohl, Alois, Hossfeld, Dieter K., Hasford, Joerg, Hochhaus, Andreas, Saußele, Susanne
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.04.2011
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzamides; Biological and medical sciences; Chi-Square Distribution; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Germany; Hematologic and hematopoietic diseases; Humans; Imatinib Mesylate; Interferon-alpha - administration & dosage; Kaplan-Meier Estimate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Piperazines - administration & dosage; Protein Kinase Inhibitors - administration & dosage; Pyrimidines - administration & dosage; Remission Induction; Risk Assessment; Risk Factors; Survival Rate; Time Factors; Treatment Outcome; Tumors; Young Adult; Germany; Antineoplastic agent; Imatinib; Enzyme; Tyrosine kinase inhibitor; Alpha interferon; Transferases; Enzyme inhibitor; Chronic myelogenous leukemia; Early stage; Malignant hemopathy; Myeloproliferative syndrome; Cancerology; Protein-tyrosine kinase; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2010.32.0598

Treatment of chronic-phase (CP) chronic myeloid leukemia (CML) with imatinib 400 mg/d can be unsatisfactory. Optimization of treatment is warranted. In all, 1,014 newly diagnosed CP-CML patients were randomly assigned to imatinib 800 mg/d (n = 338), imatinib 400 mg/d (n = 325), or imatinib 400 mg/d plus interferon alfa (IFN-α; n = 351). Dose adaptation to avoid higher-grade toxicity was recommended. First primary end point was major molecular remission (MMR) at 12 months. A higher rate of MMR at 12 months occurred with tolerability-adapted imatinib 800 mg/d than with imatinib 400 mg/d (59% [95% CI, 53% to 65%] v 44% [95% CI, 37% to 50%]; P < .001) or imatinib 400 mg/d plus IFN-α (59% v 46% [95% CI, 40% to 52%]; P = .002). Median dose in the 800-mg/d arm was 628 mg/d with a maximum dose of 737 mg/d during months 4 to 6 and a maintenance dose of 600 mg/d. All three treatment approaches were well tolerated with similar grade 3 and 4 adverse events. Independent of treatment approach, MMR at 12 months showed better progression-free survival (99% v 94%; P = .0023) and overall survival (99% v 93%; P = .0011) at 3 years when compared with > 1% on the international scale or no MMR but showed no difference in 0.1% to < 1% on the international scale, which closely correlates with complete cytogenetic remission. Treatment of early-phase CML with imatinib can be optimized. Early high-dose therapy followed by rapid adaptation to good tolerability increases the rate of MMR at 12 months. Achievement of MMR by month 12 is directly associated with improved survival.