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.

ABSTRACT

BACKGROUND: 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. DESIGN AND METHODS: 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). RESULTS: 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). CONCLUSIONS: Standard-dose imatinib remains the standard of care for pre-treated patients with chronic phase chronic myeloid leukemia (Clinicaltrials.gov identifier NCT00327262).