Second-generation BCR-ABL inhibitors for frontline treatment of chronic myeloid leukemia in chronic phase

Results from several trials in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) of dasatinib and nilotinib, two BCR-ABL inhibitors with higher in vitro potency compared with imatinib, have recently been reported. In this review, the rationale for assessing dasatinib and nilotinib in the frontline setting is discussed and data from clinical trials performed to date are summarized, including single-arm studies and randomized trials compared with imatinib. Overall, both dasatinib and nilotinib have shown superior efficacy compared with imatinib during the first year of treatment and longer-term follow-up is needed to confirm that this superiority is maintained over time. Both agents have also shown favorable tolerability profiles, although distinct patterns of adverse events are seen with each agent. Clinicians now have several effective options to treat patients newly diagnosed with CML-CP and available data suggest that dasatinib and nilotinib represent improved therapeutic options compared with imatinib.