Clonal Evolution of IDH2 Mutations in AML

Isocitrate dehydrogenase 2 (IDH2) is mutated in roughly 10% of acute myeloid leukemia (AML) cases. However, the clonal evolution of IDH2 mutations through the course of AML has not been clearly elucidated.

A study presented at December’s American Society of Hematology (ASH) virtual meeting analyzed 120 AML patients for IDH2 mutation status in diagnosis, remission, relapse, and persistent disease.

In this exclusive MedPage Today video, study author Mohammad O. Hussaini, MD, of Moffitt Cancer Center in Tampa, Florida, discusses the findings.

Following is a transcript of his remarks:

I wanted to speak to you today about our abstract, which looks at IDH2 mutations in AML. As you know, IDH2 mutations are frequently mutated in AML, and since there’s targeted therapy for IDH2-mutant AML, it becomes pretty important to understand what the clonal evolution of the mutation is through the course of AML. And this is something that’s not really been clearly elucidated.

So what we did was looked through about 6,000 patients for whom we had genomic data on to find 120 AML patients who had IDH2 mutations at somewhere along their disease spectrum. We looked at the total cohort of AML patients, there are about an even split of AML-NOS [not otherwise specified] and AML with myelodysplasia-related changes. And what we found is that there’s a tremendous amount of movement in terms of the clonal evolution with both acquisition and loss of IDH mutations, remission at relapse, and in the context of persistent disease.

And what we found also, interestingly enough, is that some of these patterns also have an impact on the survival of these patients. So particularly our major findings is that most patients do end up clearing IDH2 mutations when you can push them into morphologic remission. But in those with refractory disease, about 20% will lose IDH2 mutations, and at relapse about 22% show loss of IDH2.

So overall we have about 12% of patients who gain IDH mutations sometime in their disease course. And this usually happens in the setting of relapse/refractory AML. And these patients, along with those who remain IDH positive in remission and during refractory disease, fair worse than their counterparts.