Last year, researchers identified virtually all of the major mutations that appear to drive AML and the findings may pave the way for many more patients with AML receiving precision medicine.2
The investigators analyzed the genomes of 200 clinically annotated adult cases of de novo AML. They performed either whole-genome sequencing or whole-exome sequencing, along with RNA and microRNA sequencing and DNA-methylation analysis.
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The researchers found that AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML, according to the investigators. Study author John F. DiPersio, MD, PhD, the chief of the division of oncology and at the Siteman Cancer Center at Washington University School of Medicine in St. Louis, Missouri, said major advances are occurring in the understanding of the AML.
He explained that, thanks to new technology, there are now smaller and more efficient platforms. “Everyone hopes that the new insights will change the management of AML,” said Dr. DiPersio. “These are just pieces of the puzzle. These are complicated genetic diseases and there are a number of mutations associated with AML.”
Dr. DiPersio said AG-221 is promising and it may have an even greater role in treating AML patients when they are first diagnosed, instead of when they are relapsed. However, he said that is only speculation at this time. “We need to be cautious,” he warned in an interview with Cancer Therapy Advisor. “Leukemias tend to figure out how to overcome inhibitions.”
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AML is the second most common type of leukemia diagnosed in both adults and children in the United States and the majority of patients with AML relapse or have remitting disease. Dr. DiPersio said there is a great need for an agent that leads to a sustained response.
“We don’t know how long this therapy will last and whether it can help upfront and help patients with other mutations. A massive cottage industry is doing candidate gene sequencing. The tests are very expensive and there is an addiction to ordering these tests and they may not be always helpful,” said Dr. DiPersio.
The five-year survival rate for AML patients is approximately 24%. and it is estimated that 10,460 deaths from AML will occur this year in the US.3 Dr. Tallman said he hopes to see significant improvements in AML mortality over the next two to three years.
References
- Stein E. Tallman M, Pollyea DA, et al. Clinical safety and activity in a phase I trial of AG-221, a first in class, potent inhibitor of the IDH2-mutant protein, in patients with IDH2 mutant positive advanced hematologic malignancies. In: Proceedings of the Americal Asscoiateion for Cancer Research Annual Meeting; April 5-9, 2014, San Diego, California. Abstract CT103.
- Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059-2074.
- Cancer.Net. Leukemia-Acute Myeloid-AML: Statistics. http://www.cancer.net/cancer-types/leukemia-acute-myeloid-aml/statistics. Updated: August 2013. Accessed November 3, 2014.
