How to Handle Challenging Management Issues in AML

Diagnosis, Risk-Stratification, MRD-Monitoring 

At the 2022 Lymphoma, Leukemia & Myeloma Congress in New York, Gail J. Roboz, MD, New York Presbyterian Hospital, Weill Cornell Medicine, New York, NY offers insight into the best practices for handling challenging management issues in acute myeloid leukemia (AML). Dr Roboz discusses such topics as pitfalls in risk stratification, choosing treatment for older patients, and options for patients in remission who are not candidates for stem cell transplants.

Transcript:

Hi everyone. My name is Dr. Gail Roboz. I'm a professor of medicine and head of the leukemia program at Weill Cornell Medicine in the New York Presbyterian Hospital in New York City. I am very happy to be at Lymphoma, Leukemia & Myeloma [Congress] 2022, now back in person. I'm the chair of Leukemia Day here and had the opportunity to watch and participate in a lot of different talks. I also gave 2 myself, both of which were on the topic of acute myeloid leukemia (AML). 

One of [the talks] I called Tricks of the Trade. In that talk I tried to focus on some of the things that I think are actually currently most challenging in AML. First, it's the diagnosis and risk stratification of the disease. While looking under the microscope and finding blasts isn't necessarily that complicated, the updated ELN 2022 classification system makes it clear that the combination of cytogenetic and molecular genetic information is actually not that simple to risk-stratify the disease.

I went over in some detail what some of the, maybe, pitfalls are for risk stratification. For example, what happens if you have an NPM1 mutation, which is generally favorable, but combined with complex carrier type, which is generally adverse? Well, the adverse wins in that scenario, and I gave some other examples of how the ELN 2022 has to be really carefully looked at for risk stratification.

If you get the disease right and you are classifying it correctly, that's also helpful on the post-remission side of what to do for monitoring for measurable residual disease (MRD). Monitoring is very important. We went over that for the molecularly classified diseases like NPM1-mutated or core-binding factor AML, following those patients by PCR is standard of care, whereas following post-remission patients who don't have a molecularly defined biology is done via flow cytometry.

Among the more difficult treatment decisions in AML is to what to do with [older] patients who are in their sixties and seventies. We discussed some of the strategies of deciding between therapies that are intensive, for example, CPX-351, which would be approved for patients with [AML with] myelodysplasia-related changes versus the standard of care for older patients of azacitidine and venetoclax.

There are actually a number of scenarios in which either of those therapies might be appropriate for a patient in his or her sixties or seventies. We went over some of the retrospective data looking at patients treated with those regimens and how some of them actually have more or less the same survival, whether they're treated with CPX-351 or azacitidine and venetoclax upfront. We discussed some of the ways to try to make decisions about whether patients would be routed toward an intensive therapy versus a venetoclax-based initial treatment.

And then, once they're in remission, many of the patients may be candidates for stem cell transplant, but for those who aren't, we discussed the utilization of oral azacitidine as maintenance for patients who had intensive induction but couldn't go on to transplant. Then we also discussed some of the management strategies for ongoing cycles of azacitidine and venetoclax for patients who are not going to continue onto transplant after a non-intensive induction, but rather continue to get [azacitidine and venetoclax]. We talked about some of the dose modifications and schedule changes that are likely needed for that group of patients.

AML is a hard space at the moment—lots of treatment decisions. I hope you'll have the opportunity to watch…the presentations from this excellent meeting… on various tapes and on the website.

Source: 

Roboz G J. Challenging Management Issues in AML: Tricks of the Trade; and How to Keep AML in Remission. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022. New York, NY