Secondary Acute Myeloid Leukemia (AML): Overview

Richard Stone, MD: Welcome to this OncLive® My Treatment Approach program on improving outcomes in newly diagnosed acute myeloid leukemia [AML] and translating evidence to clinical practice. My name is Dr Richard Stone, and I’m a professor of medicine at Harvard Medical School, the chief of staff at Dana-Farber Cancer Institute, and director of translational research in the leukemia division of medical oncology at Dana-Farber Cancer Institute in Boston, Massachusetts. I’m joined by my colleague Dr Eunice Wang. I welcome my good friend and colleague to introduce herself.

Eunice Wang, MD: Thank you, Rich. I’m delighted to be here to participate in this program. My name is Dr Eunice Wang from the Roswell Park Comprehensive Cancer Center [in Buffalo, New York], where I’m with the leukemia service and the department of medicine. I’m delighted to share my treatment approach for AML.

Richard Stone, MD: Welcome, and thank you for joining us in what we hope will be an enlightening discussion. We’re going to discuss advances in the treatment of newly diagnosed acute myeloid leukemia and its impact on clinical practice. We’ll present 2 hypothetical patient cases and discuss our treatment approach to illustrate how we incorporate recent data in our practice. Let’s get started.

At least 1 of these cases, if not both of them, will have secondary AML. This term isn’t used with the utmost precision when talking about cases. But in general, there are different flavors of secondary AML. One flavor of secondary AML is treatment-related AML. These folks have had hints of cancer chemotherapy for another neoplasm, whether chemotherapy or radiation, and now they have a myeloid malignancy. Not all those patients are the same. We know from DNA sequencing of cytogenetics, which can define the biology of the disease, that some of these patients may be more treatable than others. Certainly, such patients are enriched with what we’d consider mild dysplasia-related changes, such as abnormalities of chromosome 5 and 7 in complex karyotypes as well as adverse mutations, such as TP53.

Another type of secondary AML is seen in patients who have had a prior episode of myelodysplasia, ideally documented, who now have AML. Most of those patients have what we call secondary or myelodysplasia-related cytogenic and particularly molecular abnormalities, as was shown by many doctors, especially Dr Coleman Lindsley, who showed that a lot of patients with AML who have a prior history of MDS [myelodysplastic syndrome] have certain mutations that are usually in chromatin-remodeling enzymes or spliceosome genes. Some patients who have never had a known history of MDS have secondary AML mutations. Whether those should be considered secondary AML without a history of MDS is open for debate.

The notion of secondary AML is enriched for adverse prognostic features, but not every patient has adverse prognostic features. This is a distinction to de novo AML, where there’s no history of MDS. In general, those patients are more likely to have what we call pan-AML mutations, normal cytogenetics, or favorable cytogenetics. But as I mentioned a few seconds ago, some patients with de novo AML really have secondary AML, at least biologically, so that’s a bit of a challenge.

With most patients with secondary AML—at least the ones who have less than ideal prognosis, which is the majority—what are our treatment goals? It depends on patient age, comorbidities, and philosophy about what our treatment goals would be. If a patient is reasonably young, under age 75, we might even have cure as the goal. If cure is the goal in general, a patient with adverse chromosomes or secondary AML mutations are only going to be cured if they can get to a stem cell transplant.

In general, when someone presents with 1 of these adverse AML cases, we’d consider some form of induction chemotherapy. We’ll talk in a few minutes about the possibilities for induction or initial chemotherapy. Then the goal would be to do a stem cell transplant. We know that stem cell transplants can be difficult in the subgroup of patients with secondary AML with TP53 mutations, but it’s still there as a goal for many of those patients, although it’s a distant, difficult-to-achieve goal for those with TP53 mutations or complex karyotypes.

There’s also a question about how our practice has changed since COVID-19. With COVID-19 receding, we’re somewhat back to the way we were pre–COVID-19. But during COVID-19, more patients were being treated at community oncology centers. They couldn’t or wouldn’t come to the tertiary care centers, even now with the advent of the HMA [hypomethylating agent] venetoclax as an initial therapy for many patients with AML. That’s a combination that, while not completely benign, certainly lends itself to being given to the community because it isn’t as myelointensive as standard 3+7–based regimens. We need to make sure our community oncologists are aware of how to manage that chemotherapy and deal with the adverse effects.

Plus, we have targeted agents like IDH1 inhibitors, IDH2 inhibitors, and FLT3 inhibitors. Maybe those need to be managed in a different way from how we’re used to treating patients with AML with 3+7 alone. During COVID-19, some of the patients were pretty far along when they got to see the doctors, but I’m happy to report that we seem to be back into the same level of disease that patients have when they come to the doctor. Eunice, do you want to make additional comments about secondary AML?

Eunice Wang, MD: My only comment is that it appears that we’re seeing more cases of secondary AML over time, in part because of the overall aging of the general population, and that people are living longer and developing secondary myeloid processes. I also think that as we treat more patients who have other malignancies, cancers, and conditions with things like cytotoxic agents, CAR [chimeric antigen receptor] T-cell therapy, and transplants, the subset of patients who have therapy-related AML, which is a subset of secondary AML, has also been increasing. That’s partially the result of our success in other areas that we’re starting to see that continue to rise.

Richard Stone, MD: Those are fantastic points, Eunice, and I agree with all of them.

Transcript edited for clarity.