• Andreas L Petzer, Dominic Fong, Thomas Lion, Irina Dyagil, Zvenyslava Masliak, Andrija Bogdanovic, Laimonas Griskevicius, Sandra Lejniece, Stefan Goranov, Liana Gercheva, Aleksandar Stojanovic, Dontcho Peytchev, Nikolay Tzvetkov, Rasa Griniute, Atanas Stanchev, Thomas Grubinger, Marthin Kwakkelstein, Peter Schuld, Guenther Gastl, and Dominik Wolf.
• Central European Leukemia Study Group, Internal Medicine V, Hematology and Oncology, Medical University Innsbruck, Innsbruck, Austria. andreas.petzer@bhs.at
• Haematologica. 2012 Oct 1; 97 (10): 1562-9.

BackgroundPrevious 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.Design And MethodsTwo 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).ResultsThe 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).ConclusionsStandard-dose imatinib remains the standard of care for pre-treated patients with chronic phase chronic myeloid leukemia (Clinicaltrials.gov identifier: NCT00327262).

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