New agents in the treatment of chronic myelogenous leukemia

The discovery of molecularly targeted agents that selectively inhibit bcr-abl tyrosine kinase activity, such as imatinib, has revolutionized the treatment and natural history of chronic myelogenous leukemia (CML). Treatment of chronic-phase CML with imatinib showed complete cytogenetic response rates of more than 40% in patients after failure of interferon-alpha, and more than 80% in patients with newly diagnosed CML. Patients with CML can now expect excellent long-term survival, often without major side effects. In most patients, however, residual leukemic burden remains detectable using a sensitive reverse transcription-polymerase chain reaction method. In addition, many patients undergoing imatinib therapy will either not respond or lose their response over time because of resistance or intolerance. The introduction of second-generation tyrosine kinase inhibitors (TKIs) re-establishes response in approximately half of these patients. Several agents are being developed for treating patients who experience suboptimal response to second-generation TKIs and for those who develop resistance caused by the emergence of highly resistant BCR-ABL1 mutations. This article provides an overview of novel targeted agents available for CML.