An Overview of Incidence, Diagnosis, and Subtype Classification in Acute Myeloid Leukemia

Dr. Naval G. Daver: Welcome everyone and thank you for joining me. Today, we're going to discuss recent updates in the treatment of acute myeloid leukemia. We will discuss the data in the context of guidelines, the treatment landscape, and its impact on clinical practice. So let's get started. So the first section we're going to cover is incidence diagnosis and classification of acute myeloid leukemia. So I'll take a start here. We all are aware AML is the most common of acute leukemia is about 20,000 patients or so a year diagnosed with AML. The recent data statistics published in 2022 show that we are making some progress. The survival is now around 32% for five year, but this is still quite dismal. We still need to do a lot of work. And I think there's a lot of importance and focus now being put on understanding the molecular pathogenesis of acute myeloid leukemia. So maybe I'll turn it here to you, Dr. Kasner, to just talk through what you do in your practice when you see a new patient, what are the cytogenetic factors you're looking at and what you expect as the presentation for new AML?

Dr. Margaret T. Kasner: So that's a big question, right?

Dr. Naval G. Daver: Sure.

Dr. Margaret T. Kasner: Because AML is a broad range of diseases and presentations. We have patients who might present in a more indolent fashion where maybe they saw their primary care doctor even for routine visit without any real symptoms, or some fatigue and have pancytopenia. And on the other side, we have patients who may present acutely ill from any of the complications of AML. So they may have infections, they may have a very high white count that leads to leukostasis. They may have easy bruising or even overt bleeding, all the things that can happen when your white count is too high or low and your hemoglobin is low and your platelets are low. So I think all of them though, in terms of diagnosis, we take a very similar approach, which is that we start with the oldest of the morphology. We look under the microscope to classify the patient, but really flow cytometry. So flow cytometry describes the cells that we're looking at and helps us classify a patient into a myeloid leukemia. And we may be able to sub classify them into a monocytic, but at any rate, that's going to be the first step in our diagnostic process. After that, we're going to be looking for important cytogenetic factors. And some of them, like 15, 17 translocation will put patients in a completely separate type of AML that we treat so differently from what we're going to talk about today. And others may just be, not just, but they may prognosticate for us. So a minus five or a minus seven might tell us, we have a patient with a poor risk. Then things like PCR able, which will also categorize our very initial presentation. Then we're looking at molecular factors. So, FLT3 ITD mutations are sort of its own in terms of testing because they're a PCR-based test as opposed to a genetic panel of molecular tests. And then there's a whole range of genetic things that we look at. I think we're going to get into the molecular biomarker testing in a moment, but I think that's the range of tests that we look at for every patient, no matter how they present.

Dr. Naval G. Daver: So it's a big question, and as we get more and more cytogenetic molecular information, I think we're integrating it more and more into practice. So Dr. Fathi, can you just walk us through the different subtypes of acute myeloid leukemia? What classifications are you using? Are you still focusing on morphology at all in your institution, or is it all now molecular cytogenetic-based when you see a new patient?

Dr. Amir Fathi: I think a lot of this has evolved over time. And broadly speaking, we have become accustomed to categorizing patients according to favorable, intermediate, and adverse risk. And we incorporate chromosomal data as well as mutational data in making those decisions. And that has really carried over the course of the last, I would say, decade. There have been iterations over time in terms of what falls into what category, but generally we do use cytogenetic and molecular features to make those determinations. In our institution, we use all of the above. So we look at the patient, look at their age, look at their comorbidities, we look at AML and whether it's de novo or arose from an antecedent myeloid disorder like MDS or CMML or CML. We look at the cytogenetics. So cytogenetics are quite important. If somebody has a core binding factor alteration, they generally have a better prognosis. If they have something ugly like inversion three or an MLL translocation, they in general have an adverse risk. And many of the alterations fall into the intermediate risk category. And in which group we don't really can establish whether they're more favorable or more adverse, hence the larger category. Mutations, initially we had just FLT3 and NPM1, one was unfavorable, one was favorable. But in recent years, there has been a floodgate opening of all these new mutations that we know about that underpin AML. Some we think are more favorable, some we think are less favorable. So all of this data comes together for us to get a better sense of what the AML looks like. So if you have a younger patient, for example, who has an inversion 16, a core binding factor alteration in general, we feel pretty confident that we can treat those patients with intensive chemotherapy and perhaps consolidate with additional rounds of therapy in an effort to cure them without the need for transplant. Let's say you get an older patient, and I'm just providing examples here, an older patient who has a long history of MDS and after many rounds of treatment for MDS has now progressed to AML. You know you're dealing with a more challenging subtype. Maybe they have a P53 mutation, maybe they have complex carrier type or a deletion seven. Those patients in general are going to have a tougher course, a tougher biology in terms of responsiveness to treatments. So those are important for you to gather together so you can have a good nuanced informative discussion with the patient and come up with a management plan.