The outlook for patients with acute myelogenous leukemia (AML) has never looked better. The recent identification of novel genetic abnormalities is ushering in a new era in which precision medicine may greatly extend survival among some patients with AML.

On August 13, 2014, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to AG-221 for the treatment of patients with AML who harbor an isocitrate dehydrogenase-2 (IDH2) mutation. AG-221 is a first-in-class oral agent. Currently, it is being evaluated in a phase 1 clinical trial in patients with advanced hematologic malignancies.

“So far, we have treated probably 30 patients” said study investigator Martin Tallman, MD, who is chief of leukemia service at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, New York. “I think it is a very exciting drug and we are seeing quite remarkable results. There is a reason for excitement and it is justified, but the results are early.”

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The excitement about this agent, in part, is due to its mechanism of action. Instead of killing the leukemic cells, this agent helps them mature into healthy blood cells.

This past April, Eytan Stein, MD, also of MSKCC, presented the initial findings regarding AG-221 that showed a significant number of patients who responded very quickly and that the treatment was associated with few adverse side effects.1 Dr. Stein reported that 7 out of 10 patients had complete remission following treatment with this oral agent.

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“We are seeing quite limited side effects. It seems to be quite well tolerated,” Dr. Tallman said in an interview with Cancer Therapy Advisor. “I think the next step is to treat patients early in the course of the disease and in conjunction with combination chemotherapy as an initial therapy. I don’t think it will be this year. I would hope by the end of next year.”

It is estimated that approximately 15% of AML may carry the mutated enzyme that is targeted by AG-221. Currently, the company that is developing AG-221 (Agios Pharmaceuticals, Inc.) is also conducting a phase 1 study of a second agent called AG-120, which targets a mutated IDH1 protein that affects up to 10% of patients with AML.

AG-120, which is an oral agent, is a selective, potent inhibitor of the mutated IDH1 protein. The company contends that IDH1 is an important target in the treatment of a broad range of hematologic and solid tumor cancers.