Dose escalation of imatinib in chronic-phase chronic myeloid leukemia patients: is it still reasonable?

Abstract

Suboptimal response or treatment failure to standard-dose imatinib are relevant problems in chronic-phase chronic myeloid leukemia patients. Insufficient adherence is one of the main causes of insufficient response but biological reasons also have to be considered. Various mechanisms of resistance have been described in the past, some of them mediating absolute resistance and others, relative resistance, to imatinib. The latter can be overcome by dose intensification of imatinib. However, the availability of second-generation tyrosine kinase inhibitors means these patients can be switched to these novel agents. Thus, which strategy is most appropriate for the individual patient with insufficient response to standard-dose imatinib remains elusive. Moreover, it remains unclear whether dose intensification of imatinib in the first-line setting might allow a more rapid and deeper response rate. This article will summarize data on imatinib dose intensification and will make recommendations about which patients imatinib dose intensification is most appropriate for.