Sequential therapy in chronic myelogenous leukemia: where do emerging therapies fit within current treatment regimens?

Overview

Chronic myelogenous leukemia (CML) is a slowly progressing malignancy that most often includes a clonal genetic aberration (the Philadelphia chromosome) that results in the BCR-ABL fusion protein, a constitutively activated tyrosine kinase. The management of CML was revolutionized more than a decade ago with the introduction of imatinib, a targeted inhibitor of the BCR-ABL protein. Imatinib has improved outcome and increased survival, but a substantial number of patients will develop resistance or intolerance to therapy. The second-generation tyrosine kinase inhibitors nilotinib and dasatinib are now approved in both the first-line and second-line settings. More recently, ponatinib and bosutinib were approved for resistant or refractory disease. This expansion to the treatment armamentarium has raised questions regarding the best selection and sequencing of agents. Clinical trials are now beginning to address these issues and others. The many treatment options in CML can offer patients improved outcomes, greater quality of life, and increased survival.