Standard Management of Patients with Chronic Myeloid Leukemia

The successful introduction of the tyrosine kinase inhibitors has revolutionized the treatment of patients with chronic myeloid leukemia (CML). Imatinib therapy induced high rates of complete cytogenetic and major molecular responses, and improved survival in CML. Resistance to imatinib represents a clinical challenge. The most common mechanisms of resistance include BCR-ABL kinase domain mutations, amplification and overexpression of BCR-ABL oncogene, and clonal evolution. Several approaches to overcome resistance have been proposed. The understanding of at least some of the mechanisms of resistance to imatinib has led to a rapid development of new agents that may overcome this resistance. Novel targeted agents designed to overcome imatinib resistance, include second generation tyrosine-kinase inhibitors like dasatinib, nilotinib, and others. Other approaches are exploring combination therapy, with agents affecting different oncogenic pathways, and immune modulation. Herein, we review some of these targeted therapies, particularly those for which clinical data are already available