Targeted Therapies in Chronic Myeloid Leukemia

Until 2000, therapy for chronic myeloid leukemia (CML) was limited to nonspecific agents such as busulfan, hydroxyurea, and interferon-alpha (IFN-a). The landscape changed dramatically with the development of small-molecule tyrosine kinase inhibitors (TKIs) that was shown to potently interfere with the interaction between the BCR-ABL protein and adenosine triphosphate (ATP), blocking cellular proliferation of the malignant clone. Three TKIs are commercially available for the front-line treatment of CML: imatinib, dasatinib, and nilotinib. With the updates of the DASISION and ENESTnd trials, the question often arises as to the optimal choice for front-line management of CP-CML. Based on attainment of faster and higher rates of complete cytogenetic response (CCyR), major molecular response (MMR), and complete molecular response (CMR), and a trend for lower progression rates to accelerated phase (AP) or breakpoint cluster, it is reasonable to use a second generation TKI for front-line management.