Treatment options in imatinib-resistant chronic myelogenous leukemia.

Objective: To discuss new therapeutic options available in the treatment of chronic myelogenous leukemia (CML) in patients who failed or were intolerant to imatinib therapy.

Data Sources: Literature was accessed via MEDLINE (1966-May 2007), EMBASE (1991-3rd quarter 2007), the Proceedings of the American Society of Hematology (2000-2006), and the Proceedings of the American Society of Clinical Oncology (2000-2007). Search terms included imatinib, dasatinib, nilotinib, and chronic myelogenous leukemia.

Study Selection And Data Extraction: Meeting abstracts and studies that reported preclinical and Phase 1, 2, and 3 trials published in English are included.

Data Synthesis: Imatinib is the standard of care for CML; however, some patients develop resistance or are intolerant to the drug. Phase 1 and 2 clinical data for the more potent tyrosine kinase inhibitors, dasatinib and nilotinib, are promising. Hematologic and cytogenetic responses are reported with both. There does not appear to be cross-resistance between the drugs, although neither is effective against all mutations of the hallmark molecular marker, the Philadelphia chromosome. Novel agents are also being examined for the treatment of patients with CML, including aurora kinase and farnesyl transferase inhibitors, as well as combination therapies.

Conclusions: Dasatinib and nilotinib are second-line options for patients who have CML and are resistant or intolerant to imatinib. Toxicity profiles between agents may differ. Clinical trials with these drugs and others are ongoing.