Chronic myeloid leukemia in the tyrosine kinase inhibitor era: what is the best therapy?

Imatinib mesylate, 400 mg/d, is considered standard therapy for managing patients with chronic myeloid leukemia (CML) in chronic phase, yielding high rates of cytogenetic responses that translate into favorable long-term outcomes. However, some patients do not achieve adequate levels of response, lose a previously acquired response, or are forced to discontinue imatinib therapy because of safety reasons. To avoid these outcomes, several approaches are being tested in the frontline setting, including the use of higher imatinib doses or second-generation tyrosine kinase inhibitors such as nilotinib or dasatinib, the latter of which is approved only for managing patients who have imatinib therapy failure. Newer multikinase inhibitors active against multiple ABL1 mutations are also under development for patients in any CML phase who have therapy failure on sequential imatinib and a second-generation tyrosine kinase inhibitor or carry the highly resistant T315I mutation and are not candidates for allogeneic stem cell transplantation. Some of these approaches are expected to improve the outcomes of patients with CML.