Frontline therapy with high-dose imatinib versus second generation tyrosine kinase inhibitor in patients with chronic-phase chronic myeloid leukemia – a propensity score analysis

摘要

Tyrosine kinase inhibitors (TKI) improve survival in patients with chronic myeloid leukemia in chronic phase (CML-CP), with the survival of patients treated with such agents approaching that of the general population.~(~(1),~(2)) High-dose imatinib has also been reported to induce higher rates of deep and earlier molecular responses compared to the standard dose of imatinib.~(~(3),~(4)) However, the efficacy of high-dose imatinib has never been compared to that of nilotinib and dasatinib. The aim of this study is to compare cytogenetic and molecular response rates and survival outcomes obtained with high-dose imatinib or second generation TKIs.Patients with newly diagnosed CML-CP who enrolled in four consecutive or parallel prospective single-institution clinical trials of imatinib (single-arm 800 mg daily; randomized 800 mg daily pegylated interferon),~(~(5)) nilotinib (400 mg twice daily),~(~(6)) and dasatinib (50 mg twice daily, or 100 mg daily)~(~(7)) were analyzed. Patients who received imatinib 800 mg daily + pegylated interferon were excluded from this analysis. These trials were registered at clinicaltrials.gov identifier. 00038649, 00050531, 00254423, 00129740 . The inclusion criteria were similar for all the trials, including age 15 years, adequate organ function, and performance status 02. Standard definitions for cytogenetic and molecular response were used.~(~(8)) The definition of overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS) were as previously published.~(~(2),~(3)).