Dan Pollyea, MD, MS, on the Discovery and Incidence of IDH1 and IDH2 mutations in Patients With AML

IDH1/2 mutations have been detected in nearly 20% of patients with acute myeloid leukemia.

A study of venetoclax (Venclexta) plus azacitidine (Vidaza) resulted in higher response rates, longer duration of response, and a higher median overall survival versus azacitidine alone for patients with acute myeloid leukemia (AML) harboring IDH1/2 mutations who were treatment naïve and ineligible for chemotherapy.

The results of the study, which pooled data from an ongoing phase 3 study (NCT02993523) and a phase 1b study (NCT02203773), were presented at the 2020 American Society for Hematology Annual Meeting & Exposition, and provided further evidence of an effective treatment for this patient cohort, many of whom are ineligible for intensive chemotherapy due to existing comorbidities or age.

In an interview with CancerNetwork®, Dan Pollyea, MD, MS, of the University of Colorado Cancer Center, discussed how these mutations were originally discovered.

Transcript:

We have only known about the presence of IDH in AML for about the last 10 years. It’s really a fascinating story. A little over 10 years ago, the first patient with cancer had whole genome sequencing performed. That patient happened to [have AML], and that patient happened to have an IDH1 mutation. That was published in the New England Journal of Medicine. We’ve since gone back and looked and done targeted resequencing to see what the incidence of IDH1 and IDH2 mutations are in AML; it’s upwards of 20% of patients who have these mutations, which we didn’t even know about them before. It’s really fascinating story. Add to that the fact that these are targetable mutations on their own and that there are 2 therapies that are specifically FDA approved for use in the relapse setting for patients with IDH1 and IDH2 mutations. There’s just been a lot of excitement around this in general.

Reference:

Mardis ER, Ding L, Dooling DJ, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med. 2009;361(11):1058-66. doi: 10.1056/NEJMoa0903840