Acute Myeloid Leukemia: Advances in Initial Therapy - Episode 1
Daniel Pollyea, MD, MS, explains the risk factors for acute myeloid leukemia, the importance of biomarker testing, and the challenges that prevent every patient from being tested.
Daniel Pollyea, MD, MS: Acute myeloid leukemia, or AML, is a pretty heterogeneous disease. We’ll get to some of that on the biological front. But with respect to the epidemiology, compared with other types of malignancies, it’s quite rare. There are probably around 30,000 cases a year in the United States. The risk factors for this disease are poorly understood. We think there are some environmental exposures that can cause this to occur, but those are very poorly understood. Lots of exposure to benzene in the setting of an industrial accident and radiation in large amounts are 2 examples. For the most part, we don’t know what causes AML.
There are some other risk factors that are a little more obvious. AML can evolve from an antecedent hematologic condition like MDS, or myelodysplastic syndromes. That’s a common way for AML to evolve, particularly in older patients. There are also some emerging data on some inherited genetic mutations that can prompt this. We only recently started recognizing this in the setting of some families in which this diagnosis clusters. But this is a very uncommon scenario. With respect to the prognosis, it’s very varied. With some of these new therapies that we’re going to discuss, the prognostic abilities of us to make an assessment are less accurate because of a shorter track record with some of these new therapies. The jury is out. Historically, the prognosis has been quite poor for AML, but we hope that’s changing.
At diagnosis, it’s important to collect some information from patients, because if you’re successful in getting patients into a remission, then this information will no longer be available to you. The only time you’ll have access to it is at diagnosis. Because of the importance of this information on the treatment plan on decisions such as whether a patient should get a transplant, it’s critical to get this information.
What information are we talking about? At diagnosis, you need flow cytometry, which can help make a distinction between AML and ALL [acute lymphocytic leukemia]. You need cytogenetic data, so metaphase cytogenetics is really important. There are also FISH [fluorescence in situ hybridization] panels that can be used if cytogenetics fails, or to supplement the cytogenetic data. The last is what we call molecular data, the status of any gene mutations that may be present. There are upward of 50 that are recurrently mutated in AML. There are large panels that include all 50 of these mutations that you need to send for at diagnosis because of the implications of this. This is all recommended by the NCCN [National Comprehensive Cancer Network]. These are the standard recommendations for the care and diagnosis of a patient with AML.
In addition to that broad spectrum genomic panel, if a patient is a potential candidate for intensive induction chemotherapy, one must have access to getting FLT3 mutation status within a couple of days. Because if you’re giving a patient standard induction chemotherapy, and they have a FLT3 mutation, it’s necessary to add in midostaurin by day 8. That’s a very important element as well.
It’s important to retest all these at relapse or suspected relapse. There are a couple of reasons for that. One is that the disease can evolve and change. Sometimes a patient who didn’t have a particular gene mutation at diagnosis develops it at relapse. That can be an opportunity for a targeted therapy. That’s one reason, because it can change the therapeutic approach. Another reason is to gain a more sophisticated understanding of how the disease has evolved and what the best course of action might be. In the relapse setting, the only curative strategy would potentially be a transplant. Typically, if a patient is a transplant candidate, regardless of the disease biology, at relapse, that’s the plan. But it’s really important to investigate that gene mutation panel in particular because the disease can evolve and mutations can come and go. That can give you some way to approach the disease that you didn’t before.
Not all patients are getting this recommended testing for a variety of reasons. In some cases, it’s a knowledge issue, knowing and understanding what needs to be collected and when. In other cases, there are reimbursement issues. There are also issues with respect to different institutions doing this differently. At some institutions, it’s the job of the pathologist. At other institutions, it’s the job of the clinician. Sometimes that hasn’t been clearly defined, because this is a rare disease. In a community-based oncology practice, they may be seeing only a few cases of AML a year. All those barriers are at play. But it’s really important to address them, because this is crucial for the effective treatment and best possible outcomes of these patients.
Transcript edited for clarity.