Front-line and salvage therapies with tyrosine kinase inhibitors and other treatments in chronic myeloid leukemia

Chronic myeloid leukemia (CML) has been a model disease in the development of targeted therapies. After nearly 40 years of the recognition of the chromosomal abnormality that defines CML, specific therapy was developed, initially with imatinib mesylate, which has transformed our treatment algorithms and has changed the natural history of the disease. Today, most patients have the expectation of a favorable outcome when treated with standard-dose imatinib. However, a significant proportion of patients do not achieve the optimal desirable outcome. Effective salvage therapy followed the recognition of some of the most common mechanisms of resistance. More recently, the focus has turned to new areas of research and medical need, such as improving the front-line therapy to minimize the risk of resistance, to fight the most resistant mutant forms of BCR-ABL, and to eliminate minimal residual disease with the goal of achieving total elimination of the disease and treatment discontinuation. In this review, we analyze the current status of therapy of CML, and we discuss some of the most relevant clinical questions that we face today.