Expert Point of View: John C. Byrd, MD


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John C. Byrd, MD

The study shows that AML with IDH2 mutations is therapeutically targetable with AG-221. This is a patient-friendly therapy, and it can be moved to combination therapy.

—John C. Byrd, MD

Formal discussant of the AG-221 study presented at the 2014 American Association for Cancer Research meeting, John C. Byrd, MD, of The Ohio State University, Columbus, said, “Congratulations to Dr. Stein for bringing this drug forth.”

He continued, “Acute myeloid leukemia (AML) is challenging to treat. The initial introduction of therapies is done in relapsed AML, where secondary aberrations often predominate, with lower likelihood of clinical benefit. AML is often proliferative, and virtually all AML patients have cytopenias.”

About 10% of all adult AML patients have IDH2 mutations, and these occur more frequently with age, Dr. Byrd said. IDH2 levels correlate with progression-free survival and are a good surrogate endpoint.

Impressive Data

“We would not expect relapsed AML patients to do very well. It is impressive that 16 patients remain on study. The complete response rate is notable, and there are no dose-limiting toxicities,” he noted.

“The study shows that AML with IDH2 mutations is therapeutically targetable with AG-221. This is a patient-friendly therapy, and it can be moved to combination therapy. There are some questions, including the durability of the remissions, how well the drug works for the aggressive IDH2 172 mutation, and whether there are latent side effects. Combinations and sequences will be studied. The future looks interesting for this compound,” Dr. Byrd stated. ■

Disclosure: Dr. Byrd reported no potential conflicts of interest.


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