Acute Myeloid Leukemia: Optimizing Risk Stratification

Expert oncologists reflect on risk stratification in acute myeloid leukemia and the process of categorizing patients into ‘fit’ versus ‘unfit’ subsets.


Jorge E. Cortes, MD: We’ve discussed the molecular classification, but another important classification that we must also consider is the one that we increasingly talk about, whether the patient is fit or unfit for therapy because that also has important implications as to how we manage a patient. I’d like to ask Hetty, how do you define the fitness? Is it age? Is it comorbidities? Do you use one of these scores that have been developed? How do you assess that fitness?

Hetty E. Carraway, MD: I don’t personally use a scoring system for our patients, although that is perfectly acceptable if people are using that, and certainly, for patients that are headed to transplant, they use a score to evaluate for comorbidities. I will argue that for some of our patients that begin therapy for AML [acute myeloid leukemia], they can become unfit because of the AML and how long they’ve had and been suffering from the toxicities of leukemia itself. We are often challenged with getting the results of next-generation sequencing. If a patient’s disease and tempo of disease is such that they’re in the ICU, hypotensive, have many issues with a pneumonia or some other type of sepsis, and/or involvement of the parenchyma or other types of skin involvement, for some of those patients, I move quickly and use induction chemotherapy. I don’t often wait for next-generation sequencing or chromosome tests to come back, especially in our patients that are younger and otherwise fit with very limited comorbidities. Many of our patients with this diagnosis are over the age of 65, and it’s unusual to have patients that have no other comorbidities, but it can be that those comorbidities are well managed or well controlled. For some of those patients, we can move forward with induction chemotherapy and we often can offer those in the upfront setting, especially if we have a clinical trial that they are eligible for, and in that clinical trial, it allows for the addition of newer novel agents to help with the improvement of what we expect to be the standard outcome. The same is true for patients that may be moving forward with other regimens, such as azacitidine [Vidaza]and venetoclax [Venclexta], where we have many clinical trials that use those 2 agents and offer a novel therapy. With regard to fit or unfit, we are equally filling in those classifications based on our clinical trial paradigms. For the clinical trials, they often want us to quantify or meet certain ECOG [Eastern Cooperative Oncology Group] performance status criteria to move forward on study or not. The biggest pieces to this for my patients are listening to how they were doing before they were diagnosed or having symptoms of AML. Even if they’re not fit at the current time, if you start them on therapy and reassess after the first cycle of disease, they can get better once their leukemia is better controlled. Those are things that are hard to quantify in a scoring system, and one of the reasons why we remain challenged by the definition of fit or unfit because I believe it’s dynamic more than static.

Jorge E. Cortes, MD: I agree, and as somebody who’s already up there in age, I think that we need to remember that it’s not just an age factor. There’s certainly older patients who can be very fit for more intensive chemotherapy, and there are younger patients that because of other reasons, they cannot handle it. I’m glad you brought up the issue that this should be a dynamic assessment of the patient because that can evolve. You don’t just classify them at the time of diagnosis and stay with that. They can go from unfit to fit or vice versa, and you must adjust to that and provide the best treatment for the patient.

Transcript edited for clarity.

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