Evolving treatment strategies for patients newly diagnosed with chronic myeloid leukemia: the role of second-generation BCR–ABL inhibitors as first-line therapy

In patients with chronic myeloid leukemia (CML), disease in the initial chronic phase (CP) and subsequent progression are driven by the oncogenic activity of the BCR–ABL fusion kinase. Imatinib, a tyrosine kinase inhibitor of BCR–ABL, has been the mainstay of first-line therapy for CML for 10 years. Although patients with CML–CP respond well to imatinib, those who have delayed reductions in leukemic burden during imatinib therapy, such as not achieving a complete cytogenetic response (CCyR) by 12 months, have an increased risk of disease progression. It has been recognized, with 8 years of observation, that patients who achieve an early major molecular response (MMR) on imatinib have a very low probability of disease progression. Recent randomized phase 3 trials have shown that first-line treatment with dasatinib or nilotinib—more potent BCR–ABL inhibitors—results in significantly higher rates and more rapid achievement of CCyR and MMR in comparison with standard-dose imatinib. These trials suggest that CML treatment can be improved with more potent BCR–ABL inhibition during initial therapy, but further follow-up is needed to confirm that the improved response rates with dasatinib and nilotinib are maintained long term.