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 

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 

 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.

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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 Comprehensive Cancer Center, discusses developing active therapeutic combinations for the treatment of patients with acute myeloid leukemia (AML).

At the 2017 ASH Annual Meeting, researchers discussed that clinical trials have been focused on developing active therapeutic combinations. Smith cites the benefit of such an approach in the recent FDA approval and application of midostaurin (Rydapt), an inactive single agent, in combination with chemotherapy. This resulted in an increase in overall survival (OS) in a randomized upfront trial compared to chemotherapy alone, demonstrating a 7% absolute benefit in 4-year OS.

Drugs that may not be ideal alone, when combined with the right agents, may be able to produce better outcomes. Ongoing trials of these more active second-generation FLT3 inhibitors are currently accruing in the upfront setting and the relapsed/refractory setting. These include upfront combinations with gilteritinib, quizartinib, induction chemotherapy, and hypomethylating agents.

Catherine Smith, MD, assistant professor, Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, discusses developing active therapeutic combinations for the treatment of patients with acute myeloid leukemia

Catherine Smith, MD

Articles

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