Benefits of Thorough Evaluations Before Starting AML Treatment | Samuel Yates, MD, MS | #ASH24

I'm Sam Yates. I'm a leukemia physician at the University of Chicago Comprehensive Cancer Center. So we presented a large retrospective analysis, including eight different academic centers in the United States, where we looked at the impact of time from diagnosis to treatment. So the time that a patient gets diagnosed with AML to when they receive their therapy with what's currently the frontline therapy for patients who are older than 60 called hypomethylating agents and venetoclax. And we looked at the impact of waiting to see the impact of overall survival, the time that you wait. So we think that the impact is that a lot of times patients when they first get diagnosed, they may have an infection, they may need transfusions, they may need to see a physical They may need to see a nutritionist. And we want to focus on basically optimizing a patient's care outside of just the fact that they have a newly diagnosed AML. And then often we need to wait about a week or so to get very sensitive data to better characterize the AML. And that test is called a next generation sequencing or NGS. And that allows us as treating leukemia doctors to better tailor the therapy, not just to broadly of AML, but to the specific type of AML that that patient has. First of all, we need to reassure those patients and tell them that we've studied this both in this current treatment that we use now. But over the past two decades, there have been five different studies, two of which have been in the United States, three of them have been in Europe, where it shows that overall we have time to wait and get a full, thorough evaluation. And we think that we should reaffirm to patients as well that their outcomes are likely to be better if we can get all of our ducks in a row and make sure we have the clearest picture possible before starting their journey with AML therapy. The therapy that we're describing right now that all these patients in our study received is not a targeted therapy when patients read that on HELP3 or another resource. The benefit, though, of getting that information is that there are a lot of other therapies, including the FLIT3 inhibitors that you just mentioned there, and then TP3 mutations, which can confer a worse prognosis. It allows us to better tailor the therapy that they may receive. Some of that is not necessarily in the current era of AML therapy right now, but as a lot of studies have been presented at ASH here, we have all sorts of new drugs, FLIT3 inhibitors, the Mennon inhibitors, where we're trying to combine those targeted drugs for specific subtypes with HMA and venetoclax. And from my perspective, in about five to 10 years, probably more so five years, certain subtypes like the FLIT3 mutated AML, the NPM1 mutated AML, those are going to be receiving triplet therapies, so HMA-VEN plus an inhibitor, not just HMA-VEN. Caregiver support is so incredibly important, especially the emotional support at the early time because this patient hears that they have a new leukemia. If they look online, they will see that it is an aggressive leukemia, and it indeed is. And we as treating leukemia doctors will do our best to comfort that patient and tell them that things are going to be all right. But there's no better comfort than hearing a familiar voice say, I'm taking all of this in with you, and I believe that we should take some time, get a thorough evaluation of your diabetes, your heart dysfunction, along with the AML, and let's take this time to get a full appraisal of what's going on before we start the treatment. So getting that reassurance from a family member often does better than getting a reassurance from a leukemia doctor that you just met in the hospital, right? Yeah, it's good to have this family support. Currently, we don't use a lot of TriPnet regimens. So I alluded to the FLIT3 inhibitors for IDH1 mutated AML and IDH2 mutated AML. We have targeted drugs as well, and IDH1, we have ivacidinim. And again, those combinations, those triplets are being more and more heavily studied, and I think that that is very much going to be the standard of care in five to 10 years. There's also a lot of current investigation looking at comparing HMA and VIN, which has historically been used in older patients, older than 60 years old, or unfit patients, which we define by whoever the treating physician is at that time, assessing that patient to say, I don't think they're going to benefit from what is the previous standard of care in more fit patients, which is called 7 plus 3, which is a very standard chemotherapy regimen. There's a lot of investigation going on right now, though, that may show that HMA VIN is going to do just as well as that intensive chemotherapy. And we may be able to spare patients the toxicity of getting traditional chemotherapy and being able to receive HMA VIN. That depends on the subtype of AML, though, and so we really do need to wait for that molecular data to be able to see whether we can use HMA VIN or we really do need to use the kind of beefier regimen in 7 plus 3. I think a diagnosis of AML is an incredibly frightening thing. We hear that all the time. And there's so much urgency when patients first get that diagnosis, and it's especially exacerbated because it's usually not in a calm, quiet, outpatient setting. It's in an emergency room. It's in a hospital where patients are acutely ill. Trying to recognize that we are assessing many, many things on top of just a new diagnosis of AML, we want to make sure that we have all the information about the AML to be able to choose the best treatment regimen. And then we also want to focus on not just the AML, but your other comorbidities. Are you malnourished? Do you need an evaluation from a physical therapist to do some sort of prehabilitation to make it so that you're as healthy as possible before we start? Because an AML diagnosis and the treatment, it's a long-term plan that we're coming up with. It's a long-term diagnosis, and we want to make sure that you're as healthy as possible and as strong as possible before we start the treatment.