Genetic Alterations in Acute Myeloid Leukemia

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Transcript:

Harry Erba, MD, PhD: Next-generation sequencing has led to a deeper understanding of acute myeloid leukemia [AML] pathogenesis resulting in several recent FDA approvals of novel agents. In light of these advances, we have growing opportunities to individualize therapy for each patient. In this OncLive Peer Exchange® discussion, we will discuss new and more personalized treatment options for managing AML, and emerging strategies for improving outcomes. We’ll discuss key clinical trials including data from the 2019 ASCO [American Society of Clinical Oncology] annual meeting and how the newest research will apply to your clinical practice.

I am Dr Harry Erba, professor of medicine and director of the leukemia program at Duke University in Durham, North Carolina. Participating today on our panel are: Dr Jorge Cortes, deputy chair and professor of medicine in the Department of Leukemia at MD Anderson Cancer Center, in Houston, Texas. Dr Alexander Perl, associate professor of medicine at the Hospital of The University of Pennsylvania, in Philadelphia, Pennsylvania. Dr Daniel Pollyea, associate professor of medicine and clinical director of leukemia services at the University of Colorado in Aurora, Colorado. And Dr Eunice Wang, chief of the leukemia service at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

Let’s start by reviewing the genetic testing that is needed for the optimal care of people with acute myeloid leukemia. Eunice, do you want to take us through some considerations there?

Eunice Wang, MD: Sure, Harry. As you know acute myeloid leukemia or AML is an incredibly biologically heterogeneous disease. It is a disease of immature myeloblasts, which are prematurely arrested in an early phase and don’t differentiate. And it is characterized as we are now seeing in all of the next-generation sequencing data by an incredible complexity of molecular and genetic aberrations. When we look at AML, we used to think of it as a bulk disease with a clonal tumor type. We now know through next-generation sequencing and even single-cell analysis that that’s not true. Almost every AML genome has mutations involved in it, and some of these mutations actually are incredibly helpful, both therapeutically and prognostically.

We’ve also known through sequential analysis from diagnosis, remission, and relapse that the number of clones over time in that AML population can vary. We can eradicate some of them with chemotherapy, and very frighteningly, we also have development of novel ones at the time of relapse and recurrence. So the mutations that have been identified as most prognostic include those that are most prevalent, as well as those that are rarer. The most prevalent mutations that we find in AML are: FLT3, either ITD [internal tandem duplication] or TKD [tyrosine kinase domain] mutations; IDH1/2, which is found in anywhere from 7% to 15% of AML; DNMT3A; NPM1; TP53; RUNX1; ASXL1, and many other ones. It seems like every year there are new mutations being identified, and our prognostic system, both through the NCCN [National Comprehensive Cancer Network] and the European LeukemiaNet, now lists a multitude of both cytogenetic and molecular aberrations in terms of differentiating between favorable, intermediate, and poor-risk disease.

As we move forward, I know we’re going to be talking a little bit about how identification of some of these mutations is not only prognostic but also can be therapeutic. I think it’s important to mention at this point that for many AML clinicians, next-generation sequencing using an extensive panel for all of these multiple mutations really is becoming the standard of care to allow us to optimally treat our AML patients now and in the future.

Transcript Edited for Clarity

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