Dr. Smith on Acquired Resistance to Targeted Agents for AML

Catherine Smith, MD, assistant professor, Division of Hematology/Oncology, Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, discusses patient acquired resistance in quizartinib (AC220) and gilteritinib (ASP2215) in acute myeloid leukemia (AML).

Over more recent years, more potent and selective inhibitors have been developed such as quizartinib, an active drug that resulted in composite complete remission rates of 40% to 50% in a relapse/refractory FLT3-mutant population. Responses were limited by the rapid development of resistance usually due to on target kinase mutations at the DA35 residue, also found in de novo AML.

Targeted therapies such as gilteritinib have since been developed to target these DA35 mutations. Results from the phase I/II trial resulted in complete remission rates of about 40%. However, the drug is still limited to resistance, and physicians are working to mitigate this resistance in patients.