High-dose imatinib induction followed by standard-dose maintenance in pre-treated chronic phase chronic myeloid leukemia patients – final analysis of a randomized, multicenter, phase III trial

• Published in: Haematologica (Roma) Vol. 97; no. 10; pp. 1562 - 1569
• Main Authors: PETZER, Andreas L, FONG, Dominic, STOJANOVIC, Aleksandar, PEYTCHEV, Dontcho, TZVETKOV, Nikolay, GRINIUTE, Rasa, STANCHEV, Atanas, GRUBINGER, Thomas, KWAKKELSTEIN, Marthin, SCHULD, Peter, GASTL, Guenther, WOLF, Dominik, LION, Thomas, DYAGIL, Irina, MASLIAK, Zvenyslava, BOGDANOVIC, Andrija, GRISKEVICIUS, Laimonas, LEJNIECE, Sandra, GORANOV, Stefan, GERCHEVA, Liana
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01.10.2012
• Subjects: Adolescent; Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Benzamides - administration & dosage; Benzamides - adverse effects; Benzamides - therapeutic use; Biological and medical sciences; Female; Hematologic and hematopoietic diseases; Humans; Imatinib Mesylate; Induction Chemotherapy; Leukemia, Myeloid, Chronic-Phase - drug therapy; Leukemia, Myeloid, Chronic-Phase - mortality; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Maintenance Chemotherapy; Male; Medical sciences; Middle Aged; Original and Brief Reports; Piperazines - administration & dosage; Piperazines - adverse effects; Piperazines - therapeutic use; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Treatment Outcome; Young Adult; Antineoplastic agent; Phase III trial; high-dose; Multicenter study; chronic phase; Myeloproliferative syndrome; Randomization; phase III study; Clinical trial; Protein-tyrosine kinase; High dose; Human; pre-treated; Imatinib; CML; Hematology; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Chronic myelogenous leukemia; Malignant hemopathy; Standards; Chemotherapy; Chronic; Treatment; Cancer
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2011.060087

Previous data suggest that the response of chronic myeloid leukemia cells to imatinib is dose-dependent. The potential benefit of initial dose intensification of imatinib in pre-treated patients with chronic phase chronic myeloid leukemia remains unknown. Two hundred and twenty-seven pre-treated patients with chronic myeloid leukemia in chronic phase were randomly assigned to continuous treatment with a standard dose of imatinib (400 mg/day; n=113) or to 6 months of high-dose induction with imatinib (800 mg/day) followed by a standard dose of imatinib as maintenance therapy (n=114). The rates of major and complete cytogenetic responses were significantly higher in the high-dose arm than in the standard-dose arm at both 3 and 6 months (major cytogenetic responses: 36.8% versus 21.2%, P=0.01 and 50.0% versus 34.5%, P=0.018; complete cytogenetic responses: 22.8% versus 6.2%, P<0.001 and 40.4% versus 16.8%, P<0.001) on the basis of an intention-to-treat analysis. At 12 months, the difference between treatment arms remained statistically significant for complete cytogenetic responses (40.4% versus 24.8%, P=0.012) but not for major cytogenetic responses (49.1% versus 44.2%, P=0.462). The rate of major molecular responses was also significantly better at 3 and 6 months in the high-dose arm (month 3: 14.9% versus 3.5%, P=0.003; month 6: 32.5% versus 8.8%, P<0.001). Overall and progression-free survival rates were comparable between arms, but event-free survival was significantly worse in the high-dose arm (P=0.014). Standard-dose imatinib remains the standard of care for pre-treated patients with chronic phase chronic myeloid leukemia (Clinicaltrials.gov identifier: NCT00327262).