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

作者：Petzer Andreas L^*; Fong Dominic; Lion Thomas; Dyagil Irina; Masliak Zvenyslava; Bogdanovic Andrija; Griskevicius Laimonas; Lejniece Sandra; Goranov Stefan; Gercheva Liana; Stojanovic Aleksandar; Peytchev Dontcho; Tzvetkov Nikolay; Griniute Rasa; Stanchev Atanas; Grubinger Thomas; Kwakkelstein Marthin; Schuld Peter; Gastl Guenther; Wolf Dominik

来源：Haematologica-The Hematology Journal, 2012, 97(10): 1562-1569.

DOI：10.3324/haematol.2011.060087

• CML
• chronic phase
• pre-treated
• imatinib
• high-dose
• phase III study

Background %26lt;br%26gt;Previous data suggest that the response of chronic myeloid leukemia cells to imatinib is dosedependent. The potential benefit of initial dose intensification of imatinib in pre-treated patients with chronic phase chronic myeloid leukemia remains unknown. %26lt;br%26gt;Design and Methods %26lt;br%26gt;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). %26lt;br%26gt;Results %26lt;br%26gt;The rates of major and complete cytogenetic responses were significantly higher in the highdose 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 %26lt; 0.001 and 40.4% versus 16.8%, P %26lt; 0.001) on the basis of an intentionto-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 %26lt; 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). %26lt;br%26gt;Conclusions %26lt;br%26gt;Standard-dose imatinib remains the standard of care for pre-treated patients with chronic phase chronic myeloid leukemia (Clinicaltrials.gov identifier: NCT00327262).

• 出版日期2012-10
• 单位煤炭科学技术研究院有限公司