Moving toward targeted therapies in acute myeloid leukemia.

Advances in genomic sequencing and insights into molecular leukemogenesis are opening the door to using targeted agents to tailor treatment for acute myeloid leukemia (AML) in individual patients. Although this shift away from traditional cytotoxic therapies represents an innovative approach to AML therapy, a number of obstacles stand in the way of widespread adoption of targeted therapy into daily practice. For example, the effects of single agents are marginal, and the degree of variability among patients is great. Some have advocated incorporation of newly identified biomarkers into clinical trials to guide patient-specific treatment, but the relevance of these biomarkers to clinical response is uncertain and requires further validation. Combining targeted agents with other targeted agents or with conventional chemotherapy to overcome the biological heterogeneity of AML may enhance treatment efficacy; however, drug toxicities also are increased and drug resistance continues to occur. Overall survival is an impractical endpoint for clinical trials of AML, which may be addressed by using the endpoint of event-free survival to evaluate novel targeted agents. Another barrier to implementation is the high cost and limited availability of targeted agents. Herein, we address the above practical questions and propose potential strategies for the future evaluation of targeted treatments.