Combinations are the Future in FLT3-Mutated AML - Episode 1

Overview of FLT3-mutated AML

March 31, 2021
Jessica K. Altman, MD, Northwestern University

Naval G. Daver, MD, MD Anderson Cancer Center

Jessica K. Altman, MD, and Naval G. Daver, MD, share their approaches to genetic testing for FLT3 and other actionable mutations in acute myeloid leukemia (AML).

Jessica K. Altman, MD: Hi everyone, my name is Jessica Altman. I am speaking to you from Chicago. I am a leukemia physician at Northwestern University. I’m very excited to be here today with my friend and colleague, Dr Naval Daver, from MD Anderson Cancer Center in Texas. Today we’re going to spend some time getting into the nitty gritty of FLT3 mutations. Before we do that, I’d like to ask Naval to introduce himself.

Naval G. Daver, MD: Hi, thanks Jessica. It’s an absolute pleasure for me as well to be discussing this very interesting topic that we both do a lot of research on—FLT3 mutations in AML [acute myeloid leukemia]. I am a leukemia physician at the MD Anderson Cancer Center in Houston, Texas. My focus is in leukemia therapies, and one of the areas of interest is FLT3.

Jessica K. Altman, MD: Over the last number of years, we’ve developed an increased understanding of the genetics of acute myeloid leukemia. In addition to cytogenetics, it’s important to assess for mutations. Naval, what mutations do you check for routinely in your patients with newly diagnosed acute myeloid leukemia?

Naval G. Daver, MD: Our approach is very similar to what most academic centers in the US are doing. When we see a new patient with AML, we do a bone marrow biopsy, usually same day. Then we rush the cytogenetics, including FISH [fluorescence in situ hybridization] probes for core binding factor, inversion 16, 8;21, as well as for acute promyelocytic leukemia [APL] and translocation 15;17. Those are usually very quick. Usually within 24, 48 hours we know if we have one of these favorable, targetable cytogenetic groups, which of course takes us in a separate direction when making treatment decisions.

We rush the molecular panel in parallel. That takes about 4 to 5 days. We have a rapid molecular panel of only 9 or 10 genes, but they are the important prognostic therapeutic genes—FLT3, NPM1, IDH1, IDH2. Now we also include TP53 because we are using some TP53-directed therapies. These are the main mutations. CEBPA is another one.

Then maybe another week later, so around day 10, we conduct the broader 81-gene panel. But really, what we need to know is that APL is ruled out, core binding factor, and then we need to know if there is a FLT3 mutation; and if we have trials, then IDH, TP53. That’s our general approach. What about you? What is your timeline for those tests?

Jessica K. Altman, MD: Sure. We are also very lucky to be able to get rapid preliminary cytogenetic results, so it’s pretty rare that I do directed FISH studies because I can get preliminary cytogenetic results within 1 to 2 days. Certainly, that’s not the complete 20 metaphases, but if we have dividing cells we can get preliminary results. We do a next-generation sequencing [NGS] panel that’s limited to about 40 genes, and we can get results in about 5 working days. We do our FLT3 results separately, just because sometimes, as you know, the long internal tandem duplication mutations are not picked up by NGS. We’ve not missed a FLT3 mutation via NGS, but we have that PCR [polymerase chain reaction test] there just in case. Just like you, we like to ensure that we know about the mutations that are both clinically actionable and impact prognosis, and we like to have those results fairly quickly.

Transcript Edited for Clarity