Second-generation TKIs: which and when?

Impressive response rates and good tolerability have led imatinib 400 mg once a day to become the standard frontline therapy for chronic myeloid leukemia (CML) patients. However, approximately one-third of the treated patients do not respond in an optimal manner to this drug, and the appropriate type and rhythm of CML monitoring, as well as the correct action to be undertaken in case of failure or suboptimal responses to imatinib therapy have been published in specific recommendations by European Leukemia Net and National Comprehensive Cancer Network. Failure and also cytogenetic suboptimal responses strongly demand for a change in treatment and for a switch from imatinib to one of the two second-generation tyrosine kinase inhibitors (TKIs) so far registered, dasatinib and nilotinib, for which efficacy as second-line therapy in imatinib-resistant or intolerant cases has been clearly demonstrated in phase II studies, and for which 4-year updates are now available. Other TKIs, at the moment, still under clinical investigation for imatinib-resistant patients include bosutinib and the next-generation TKI ponatinib. Different efficacy and safety criteria characterize each of the mentioned compounds and may help to decide on the one to be preferably used in individual patients.