The Paradigm of AML Care: What’s New and What’s Changing

Daniel Peters, MD

Acute myeloid leukemia (AML) is both a rare and difficult-to-treat cancer, although experts across the world seek to discover new treatments and optimize patient care. Among them is Daniel Peters, MD, an assistant professor of Hematology and Oncology in the Department of Medicine at the Medical College of Georgia of Augusta University and bone marrow transplant & cellular therapy faculty member at Georgia Cancer Center, who diagnoses, treats, and guides patients through the transplantation process.

During a visit to Georgia Cancer Center, CancerNetwork® spoke with Peters about the current state of AML care. Among the topics discussed, Peters highlighted prevalent treatment strategies and the toxicity associated with each therapy. He also discussed the FDA’s recent approvals of revumenib (Revuforj) and ziftomenib (Komzifti) in NPM1-mutated AML.1.2

Read the full discussion here:

CancerNetwork: What do current treatment strategies look like for patients with AML, and what factors do you consider when selecting one therapeutic approach over another?

Peters: There are 3 main pillars that I think about with patients who come in with newly diagnosed AML. The first and foremost is the patient's condition. What is their baseline level of health or functional status when they first come in with this really challenging hematologic malignancy? Is this a younger, fit patient who doesn’t have a lot of other medical problems or [as many] comorbidities as an older patient who has chronic medical conditions [such as] heart failure, liver or kidney dysfunction, etc? That’s the first thing in thinking about what kind of treatments they’re going to be eligible for. Alongside that, [we are] thinking about what our goals of care are. For patients, are we shooting for cure? Are we shooting for prolonged disease-free survival and keeping things at bay as long as possible? Or are we thinking about palliative/supportive care to make life as comfortable as possible for that period? The other really important pillar is based on genomics, so thinking about what type of cytogenetic or molecular abnormalities a patient has is obviously very critical in this day and age for guiding our frontline treatment for patients who have AML.

What notable toxicities may occur during treatment for AML, particularly with some of the different immunotherapy approaches? How can clinicians best manage these toxicities while supporting quality of life?

For the standard intensive chemotherapy, we’re still stuck, for the most part, with 7+3, which is an anthracycline along with cytarabine. These are the [adverse] effects and toxicities that most patients will think about in movies or TV shows. You have prolonged periods of myelosuppression or low blood counts. You have things like nausea and vomiting requiring frequent transfusional support with red blood cells/platelets. You’re at high risk for infection when the blood counts are low, so you’re at risk for fever. For the most part, these patients are going to be admitted to the hospital, and [we]...support with transfusions of red blood cells/platelets; getting IV antibiotics; and [mitigating] the nausea, vomiting, hair loss, and [other] types of [adverse] effects.

Going down the lower intensity treatment pathway, the standard of care in this day and age is the combination of azacitidine [Vidaza] plus venetoclax [Venclexta]. With the toxicities, there’s some overlap. This is a pretty myelosuppressive regimen, so patients are increasingly being treated with this regimen as an outpatient. The most common things that we’ll see with this are myelosuppression [and] febrile neutropenia. It’s about a coin flip in patients who are treated with this regimen, so there’s a high likelihood that patients treated with this will have fever and end up back in the hospital. They’re also going to need intensive transfusional support with red blood cells and platelets for the first cycle or 2 until the leukemia is under control. Those are the main toxicities in broad strokes.

Unfortunately, there aren’t a ton of immunotherapies approved yet. In this day and age, for AML, we don’t have immune checkpoint inhibitors like in solid tumors. We don’t have a lot of good CAR T-cell options yet, but probably the most notable immunotherapy, at least in AML, is going to be gemtuzumab ozogamicin [Mylotarg], which is commonly given in the upfront setting to patients who have favorable or core binding factor leukemia. The most notable toxicity with that is going to be hepatic dysfunction, or liver dysfunction, so just watch the liver enzymes.

The other toxicity I’ll mention would be those associated with some of the targeted agents that we have available. Circling back to what we talked about at the beginning, “How are we treating our patients up front if they have one of these molecular mutations that has a targeted agent?” [There are] FLT3 inhibitors, [like] quizartinib [Vanflyta] or midostaurin [Rydapt], [for] one of the IDH1/2 mutations, and now, newly approved, there are some inhibitors of menin that are also out there. With these targeted agents, the big toxicity to think about or look out for is differentiation syndrome, which, in short, is where the leukemic blasts are released from their primitive stage, and they differentiate. They can cause a lot of problems. The big things to look out for are fever, shortness of breath, weight gain, and fluid retention. That’s important for both the clinician to know, but also [for] patients being treated with these regimens to be aware of, so that they can look out for them and have them addressed quickly.

The FDA recently approved ziftomenib and revumenib as options for patients with relapsed/refractory NPM1-mutated AML. How do you anticipate these newly approved menin inhibitors impacting patient outcomes in the future?

This is probably one of the more exciting developments in AML in the last 5 or so years. We now have not 1, but 2 new targeted treatments approved in relapsed and refractory AML, which is a big deal for us. Revumenib is now approved in the relapsed/refractory setting for KMT2A-rearranged, as well as NPM1-mutated, AML. Ziftomenib is approved now for NPM1-mutated relapsed and refractory AML. There are a couple of agents, other menin inhibitors, that are still being assessed in clinical trials.

What early-phase clinical trial and translational research are you involved with at Georgia Cancer Center? How might this research help improve outcomes for those with AML or other disease types?

AML causes a lot of immune dysfunction, and by immune dysfunction, I mean dysfunction in the normal patient’s immune system that’s just trying to live its life and do its job. One of my interests is to look at what these drivers of immune dysfunction are; what cellular components or subsets are dysfunctional in a patient’s immune system; and which of these cells can be targeted, exploited, or removed in hopes that we can create less intensive cellular therapy approaches for patients with AML. For patients who are going down this pathway of receiving the azacitidine and venetoclax, are there perhaps autologous cell therapies that we could use that would avoid some of the big [adverse] effects that you’d get with graft-versus-host-disease or bone marrow transplant? Or are there other ways to exploit the host immune system to augment or improve outcomes with standard allogeneic stem cell transplant?

Another thing I’ll just say is that I uniquely have the opportunity and privilege here at the Georgia Cancer Center, with my position, to both diagnose and treat patients with AML and take them up to and through the transplant process in and of itself. In a lot of other centers, the leukemia care and the transplant care are partitioned, but here, I can actually do both. That enables me to do some of these translational projects and some other research that I’m interested in.

How would this translate into benefiting patients? Essentially, what I’m hoping to do is find new therapies that are going to improve outcomes, cause less [adverse] effects, and be more accessible to a variety of patients who have AML.

How can clinicians work together more effectively to better deliver personalized treatment strategies to those with AML or other malignancies?

The important thing to stress is that none of AML or leukemia care happens in a vacuum. Here at the Georgia Cancer Center, we take care of patients across the state of Georgia and South Carolina. Many of our patients are coming from 2- or 3-plus hours away. A lot of their care is and should be anchored in the community. Our job is to serve as a good resource for the community providers. We can be easily reached, and we assist in rapid diagnosis, evaluation, and workup for these patients. In patients who are younger and fit, thinking about who would be eligible for clinical trials—those are always patients whom we would love to help take care of and get enrolled in clinical trials that could potentially be impactful. But again, none of this happens in a vacuum. We’re here to be a resource for the community, and my mindset is never to take a patient from a community practice provider. It’s to share this important responsibility of taking care of these patients as best as we can.

When you look towards the future, where does the field as a whole need to head in order to further optimize outcomes for patients with acute leukemias and other high-risk hematologic malignancies?

There are going to be some things presented at the upcoming 2025 American Society of Hematology Annual Meeting (ASH) that I think are going to change the treatment paradigm, potentially in AML. I think the field is moving towards leaving this old paradigm of 7+3 intensive chemotherapies for newly diagnosed patients with AML who are young and fit, and it’s looking at some of these other regimens, particularly azacitidine and venetoclax. That’s going to be an interesting story to watch. The field [may] move towards a less intensive approach and a less toxic approach up front. Also, another interesting story that’s going to be borne out as there’s more adoption of this azacitidine and venetoclax regimen up front is, how do additional targeted agents fit into that? This is going to be a big thing that the field needs to work out. Should we be doing triplet therapy—azacitidine, venetoclax, plus one of these targeted agents that we’ve talked about today? Is it going to be the sequencing of therapy? Is it something else? Those are questions that are going to need to be answered in the field.

References

1. FDA approves revumenib for relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation. News release. FDA. October 24, 2025. Accessed November 25, 2025. https://tinyurl.com/2s5fenvy
2. FDA approves ziftomenib for relapsed or refractory acute myeloid leukemia with a NPM1 mutation. News release. FDA. November 13, 2025. Accessed November 25, 2025. https://tinyurl.com/2mcsxzuv