In this episode, we’re joined by Dr. Samuel Yates, a researcher focused on leukemia in older adults, to talk about a topic that’s often on the minds of AML patients: how quickly treatment should start after diagnosis. Dr. Yates walks us through new research looking at “time from diagnosis to treatment” in patients receiving the now-standard combination of hypomethylating agents and venetoclax.

His findings suggest that for some patients, taking a little extra time to wait for genetic test results and assess overall physical fitness can actually lead to better outcomes. These findings challenge the long-held belief that immediate treatment after diagnosis is always best. Dr. Yates also breaks down what genetic testing really means and why it’s so important in guiding today’s more personalized treatment approaches.

He expands on what researchers around the world are learning about timing and treatment for AML. The study Dr. Yates led focused on the now-common combination of hypomethylating agents and venetoclax, especially for older adults. They found that patients who started treatment after 14 days from diagnosis had better survival—likely because doctors had time to gather more genetic information, assess the patient's overall health, and help them get physically ready for their AML treatment.

This suggests that, for many patients, taking that extra time may lead to more personalized, better-targeted care, without worsening outcomes. Ongoing trials may even show that these newer, gentler treatments work just as well in younger patients, with fewer side effects. 

Here at HealthTree, we will keep an eye on this important line of research and keep our audience up to date on any advances made so you can have educated conversations with your doctors and make sure you are receiving the best treatment for your specific case of AML. 

Mary (00:00)
Hi everyone, welcome to the first episode of the 2025 season of the Health Tree Podcast for AML, where we connect patients with AML to the research and information they need to know about. If you've been with us before, welcome back. If this is your first time joining us, welcome. We are so happy to have you join our AML podcast community.

My name is Mary Arnett. I'm your host and AML education manager here at the Health Tree Foundation. The goal of this podcast is to make research and new information coming out about your disease easy to understand and easily accessible. If you've ever found yourself overwhelmed by clinicaltrial.gov or a medical abstract, we are here to change that. The theme for this season is exploring breakthroughs in equity and AML treatment. So come back each Monday for the next few weeks as we explore these topics and see what the research tells us.

The topic of today's podcast is, does delaying treatment impact survival? This is specifically pulling from an abstract titled, "impact of time from diagnosis to treatment on outcomes of adults with AML treated with HMA and Venetoclax, a US-based multi-center real-world retrospective analysis from the Consortium on Myeloid Malignancies and Neoplastic Diseases". Yes, that is a mouthful, and we are going to get into all of that here in just a minute. I'll link this in the episode description for anyone who wants to read the actual abstract itself.

We're gonna be joined here in just a few minutes by Dr. Samuel Yates, a researcher on the study I just mentioned. Before we bring him on, I wanna give you just a little introduction. Dr. Yates is a researcher interested in hematologic malignancies, especially in leukemias like AML, and older adults with a specific interest in assessment and intervention of nutrition and body composition in these patients. I chose Dr. Yates and the topic of treatment timing and AML care for today's episode because this is a topic I see a lot of discussion on in various forms within our AML community. An AML diagnosis can often feel like a whirlwind of information, decisions, and treatment. New research we'll get into today suggests we might be able to slow things down just a little bit.

Stick around until the end of the episode when I'll be back to share my final thoughts on today's interview, as well some additional resources you can dive into related to today's topic if you just want to keep learning. Now, without further ado, let's bring on Dr. Yates.

Mary (02:15)
Okay, Dr. Yates, thank you so much for joining us today.

Sam Yates (02:18)
Yeah, thank you so much for having me. Happy to be here.

Mary (02:22)
So I like to start all of our episodes with the why behind research. So what problem or issue did you see in the AML space that you're hoping to fill with this research?

Sam Yates (02:31)
Yeah, it's a great question. the majority of the work, actually all the work that has been done looking at the time from diagnosis to treatment in patients with AML was done before the approval of the standard of care for the majority of our patients who are older adults and even some younger patients, which is the hypomethylating agents and benetoclax, which many of your listeners are probably very familiar with. And so all of the studies before and there are five of them, three of them in Europe, and two of them in the United States have been done in what's called the seven plus three era. And so besides one study that was done in Germany, there really was not much data for patients who were receiving what's the de facto kind of standard of care, particularly for less fit patients. So we wanted to try and answer that question to the best of our ability with the data that we had.

Mary (03:22)
So brief overview, what is the study we're gonna be talking about today and why do believe it's important for AML patients to understand?

Sam Yates (03:32)
so this is where we call a retrospective study, meaning we looked at data that was available at each of our centers. And so there's a large what we call consortium of centers. There's about eight to 10 of us who are a part of this group where we share data together. And we each looked at all of the patients in our center who had been treated with AML, who had been treated with the combination of a hypomethylating agent. So that could be azacitidine or decitabine and then venetoclax. And we looked at the time from the date that the patient was diagnosed up until the date that they started that therapy. And we looked at the impact that the amount of time that that had had on their survival. Importantly, we wanted to make sure as is really important in any study that you're doing with retrospective data when you're looking back, those studies can be very susceptible to bias. And so you have to get very granular information about each of those patients, meaning the exact therapy that they got. So how many days of the, know, the vanitex pills did they get? What comorbidities did they have at the time of diagnosis? How fit were they? Which is a very important marker, which we'll probably talk about moving forward as well. Whether those patients got transplant, those sorts of things.

We collected that data overall, had 488 patients between these eight centers and we're able to then look at for patients who are treated before 14 days versus at 14 days or more from the time from diagnosis to treatment and see the impact of survival. And what we found was that those who were treated the later time point actually did better from a survival perspective, even when controlling for important kind of intuitive prognostic factors for survival, meaning the aggressiveness of the disease, how healthy those patients were at the time of diagnosis and those sorts of things.

Mary (05:33)
So I wanna really get into the research itself. you just touched on what TDT or time from diagnosis to treatment is. So why does this play such an important role in AML treatment and in overall AML patient care?

Sam Yates (05:41)
Yeah. as your listeners are probably very well aware, which is a wonderful thing. There are more and more drugs available for patients with AML these days in comparison to, you know, 10, 15 years ago when I, you know, I alluded to what we call kind of the seven plus three era, the intensive induction era, where it was, it was largely chemotherapy based regimens. Now we have increasingly these targeted drugs. So drugs that target a mutation in FLIT3, drugs that target mutations in IDH1 and IDH2, the newly approved MENIN inhibitors. So all of these drugs are very exciting. As we're kind of alluding to though, you need the mutational profile of that patient's AML. And so there's actually not publicly available data on how long these mutational tests, what we commonly call next generation sequencing tests, take to come back. It kind of varies from centers to center, but increasingly it's getting faster. It's still for the readily actionable ones in between, around five to seven days. And then some of them can take up to two weeks. And so we thought it was very important as we move into this era where there are more and more treatment options to be able to figure out, know, what is, what does the data show in the era where patients are readily primarily being treated with a hypomethylating agent and vanita clots on the amount of time that it is safe or not safe to wait for that information.

And then the other piece that we think is really important and is the core of what my research is about is how long do we have to evaluate patient fitness for anti leukemic therapy? Fitness is a very, very broad term and I will say is one of the highly debated topics in the world of AML right now. Again, is one of my big area of research interests. But broadly speaking, we think about it as the ability of the patient to be able to withstand the toxicities that unfortunately come with the therapies that we give. And that information can take some time to gather. the pieces that go along with that are what comorbidities do they have? What does their life look like before the diagnosis and then currently in the diagnosis? So are they able to take care of themselves at home or not, are they able to work or not, how physically active are they, all those things can be really informative of how well a patient may tolerate the therapy, which then obviously translates into longevity on that therapy. And importantly, it's not just assessing a patient's fitness, but then being able to optimize it in certain circumstances.

So if we have patients who have lost 30 pounds of weight in the last couple of months, it would be really nice if we had the time to be able to optimize those patients beforehand. so getting an idea of how long is reasonable to potentially wait if we wanted to optimize the patient and to get those, you know, those genetic testing results back was really the basis of what we were really trying to get at.

Mary (09:00)
I'm glad you brought up patient fitness. think that's something amongst our patients and our patient focus groups or Facebook groups, we see a lot of patients talking about these other factors that influence their overall health and they're always curious, is this gonna affect my ability to get treatment? Is this gonna affect my ability to get transplant? And so I'm glad you addressed those topics and I'm excited to see how some of that plays into.

Sam Yates (09:13)
you

Yeah.

Mary (09:29)
more of this study and more of the outcomes. You also mentioned genetic testing that a lot of patients are now being given at diagnosis. Can you explain a little bit for people who are unfamiliar what that testing overall is trying to accomplish?

Sam Yates (09:35)
Mm-hmm.

Yeah. So when I explain this to patients, I usually break it down in two ways. So the first thing that we're looking at is the very small changes in DNA and we call those the mutations. And those are the things that patients probably see online, the FLIT3, IDH1, the IDH2, the TP53. So those are small changes in the DNA and those are what we're getting when we order a next generation sequencing panel.

And depending on the institution or the practice that these patients are at, it can sometimes have different names, and there's different companies who do them. So that's number one. And then number two is we're looking at the large chromosomal changes as well. And so sometimes there are extra chromosomes in the AML cell in and of itself. And sometimes they're missing chromosomes. And then sometimes pieces of the chromosomes switch with each other. call those translocations. And so

When a patient has a new diagnosis of AML, we need each of those things to basically fill out what's our basically version of a staging. Patients commonly ask me, you what stage am I thinking in the kind of mindset of someone with breast cancer or lung cancer? Because blood is everywhere. We can't do just based off of location or depth. And so we look at these genetic changes to be able to figure out how high risk is someone and how

Mary (10:54)
Right.

Sam Yates (11:08)
likely is their ability to be able to respond to chemotherapy alone or needing something potentially as aggressive as an allergenic stem cell transplant. So we need all of those pieces of information to guide us in our initial treatment decision at diagnosis.

Mary (11:23)
Thank you for explaining that and giving that context. think there are so many things that happen at that initial diagnosis for patients, especially with something like AML. moves really fast. And a lot of times I think some of that gets missed, especially early on. And so I think that over saturation of information, it's a nice to get a little refresher sometimes. previous.

Sam Yates (11:29)
Mm-hmm.

Mary (11:44)
knowledge before this study. What did we know already about time from diagnosis to treatment and how it affected outcomes? And then what did we start to learn from this study itself?

Sam Yates (11:56)
Yeah, so there were, I would say five big studies that have looked at this question over the past 15, about 15 years now. So there were two large cohorts out of the United States and they found that in patients younger than 60 years old, it was better to act quicker. And I believe the cutoff was less than or equal to five days. And then for those who are older than 60, it made no difference.

I will go ahead and mention this. 60-year-old cutoff is kind of arbitrary, as I'm alluding to the 60-year-old over and over, but that's how we generally define older adults, which is very important in determining whether we use a 7 plus 3 type regimen, an intensive induction, or an HMA and phenethyclate space regimen. And then the three European cohorts, again, one from France, one from Sweden.

I believe the other was from the UK, found no difference either in younger patients or in older patients who were receiving intensive induction regimens. I should mention as well, there was a study that came out about six months ago from Germany where they looked at venetoclax-based regimens. So it was not all venetoclax and hypomethylating agents. Some of them had less common regimen in there as well, but they also looked at this question for patients receiving venetoclax. What was the impact of from diagnosis to treatment and they found no impact on the patient's survival. One was a smaller real world cohort where they had some granular data of around 100 patients and the other one was using kind of electronic health record population based data but they also found no difference in outcomes.

Mary (13:34)
Interesting. And it's interesting that the studies here found the difference for the younger patients and the studies abroad weren't finding those same differences. Did they both include the same demographics or similar demographics?

Sam Yates (13:49)
Yeah, they did. And there's been a lot of discussion and debate over the years of what can account for that difference. And honestly, no one I think has a really great answer. Some of it may reflect slight differences in terms of treatment patterns in Europe versus Europeans often will use kind of a double induction regimen versus we don't as commonly use that in United States. But it's an ongoing and very open question of

Why did they find those slight differences in outcomes? think a lot of that is not... The question has changed a little bit, I think, in this era where we do have these next generation sequencing tests to really guide our therapies a lot of the time, because, again, with so many new drug approvals, which are dependent on the mutational profile of the AML...

Sam Yates (14:44)
To me, you really need to know that information before diving into treating a patient.

Mary (14:53)
Yeah, we're starting to see our community of that AYA younger population growing. And so we've been putting more resources and effort and we have several other, at least another episode in this podcast series talking about research into the AYA population. So it's always interesting to see when they pop up. Cause there's not as much research there as in other areas.

Sam Yates (14:59)
Mm-hmm.

Yeah.

Yeah, and that is a close mentor and colleague of mine is Wendy Stock, who is a beloved AYA oncologist here at the University of Chicago. And it's funny you bring that up because that comes up a lot in our clinic. We have an AYA clinic on Tuesdays. patients are obviously, they want to be rid of their leukemia, but they also don't want significant disability incurred based off of those regimens.

So I mentioned at the outset that our study focuses on patients who receiving hypomethylating agents and venetoclax, which as many of your listeners probably know, was primarily studied in older patients and patients who are considered unfit based off of certain comorbidities. And this was approved back in 2020 or maybe early 2021. There's a lot of ongoing trials though that are looking at comparing these hypomethylating agents and venetoclax to those intensive induction regimens, which are certainly more toxic, even in younger patients. So there may be a chance that in the coming years that we don't use those more intensive induction regimens and we use these gentler regimens that work just as effectively, but don't have as many toxicities. They certainly still have their own toxicities, but it doesn't come at least with a three to four week hospital stay, which is a wonderful thing.

Mary (16:41)
Yeah, definitely. We'll keep our audience updated on the research in that field. It's exciting. So you just talked a lot about the hypomethylating agent and Venetoclax and the intensive chemotherapy idea. So this study focused on hypomethylating agents and Venetoclax instead of intensive chemotherapy. Can you talk a little bit about the decision for that?

Sam Yates (16:44)
Mm-hmm.

Yeah, so the median age at diagnosis for acute myeloid leukemia is 69 years old. So the majority of our patients fit into that older adult category. And so the majority of patients are getting this regimen. And again, there was just a lack of data, you know, this group of patients and because it's the most common regimen that we're utilizing now, and I would say around the world as well, we thought it was very important to focus on that group and especially because some of the cohorts that had come out in the intensive induction regimens, were the German cohort in particular was I think a couple thousand patients. So we didn't think it was important to really add to that data. We didn't think we were going to add anything novel and we thought it was a very important question to provide some data to the field about those who receiving epimethylating agents in Vanita Clack.

Mary (17:59)
let's get into the findings. So how was the study conducted first? And then what were some of the key findings that you guys saw come out of this?

Sam Yates (18:04)

Yeah, so this was a retrospective cohort study, which basically just means we each at each of our individual institutions are having a data safety agreement, of course, amongst these institutions, looked at the patients within our institution who have been treated with HMAs and venetoclax and collected again, these important covariates. the comorbidities that patients have, their performance status which is an important kind of marker for trial eligibility is why we make sure to always collect that. The genetic profile, which we were alluding to earlier, so how aggressive or high risk is the disease? And then the presentation that these patients had when they were first diagnosed, meaning how sick were they? And did they require certain medications or a certain procedure, what we call leukophoresis? So sometimes we will actually pull off the leukemia cell using a central line which is very rare to have happen, but it's kind of a sign of a very aggressive disease. And those are important co-founders when you're trying to figure out, how long can you wait? And we then collated that data as a group within our consortium and looked at the data with our primary outcome and the main focus being how long did patients survive?

So when we looked at that data and we, using a statistical approach that our lovely statistician is, which is way over above my head, the optimal cutoff was 14 days, which is two weeks, which is also a very convenient cutoff for us because that is an important time point, I would say, for turnaround time for that mutational profile. So we looked at patients who were treated between one and 13 days from the date of diagnosis to the date of treatment to those who are treated at 14 days or after.

And those who were treated at 14 days or after in comparison to those who were treated from day one to day 13 had better survival. And we importantly, in this analysis controlled for how aggressive the disease was at diagnosis, the risk score that is commonly used throughout the world for dividing how high risk a patient's AML is. And we also control for how healthy those patients were when they started their therapy. It is not completely intuitive, I think, for some people to think that it's better to wait for the therapy. But we actually have that hypothesis that we thought it actually may benefit patients to wait. And the reason for that, from our perspective, is that when you get more information about a patient's AML, you're able to make a more informed decision.

And also that these patients are very likely benefiting from the ability to have a nutritionist see them, a physical therapist see them. You know, if they have underlying heart disease or lung disease that comes up when we're, know, anytime we have a new patient with AML, they automatically get an ultrasound of their heart. They get a CT scan at their chest. If there's things that we see, we try and evaluate those and optimize those before starting therapy. And we think even though we did not collect data on what optimization strategies were done, we think that, you know, over when you pull data over 500 patients, that's probably what's translating into into better outcomes. The other question that I very commonly get and came up at the talk at Ash in December is how do you know whether those patients who were waiting for those NGS results who may have passed away

How do you make sure that there was not a bias there? And fortunately, the trial that again, your listeners may be very familiar with the beat AML trial that has been going on through the leukemia lymphoma society, which is just incredible and massive undertaking of many institutions throughout the country. And the goal of that trial was to see whether you could incorporate, was to answer that question basically, could you incorporate next generation sequencing or mutational profile results into patient's treatment and not impair their outcomes and actually improve their outcomes. And they collected the data on whether how many patients were enrolled in that trial, but then passed away before they could get their results of the mutation profile. And it was around 1 % of their cohort. It was like six patients. So we did not collect that data for our study. was not possible to do so. But we think that

Mary (22:30)
yeah

Sam Yates (22:45)
With such a small effect size, we don't think that that would influence the results of our study.

Mary (22:51)
A lot of interesting things to dive into with that. So from the very beginning, like you said, that feels very counterintuitive to a lot of people, especially when they get this diagnosis of AML and maybe they're looking it up online or just from the conversation they have with their doctor, they see how aggressive this disease can be. And especially with how therapy and treatment has gone in the past where it is very much you get your diagnosis and you start treatment immediately.

Sam Yates (22:53)
Haha

Mary (23:20)
that could give the patient who is being told that it's okay to wait a lot of anxiety or nerves surrounding that. what would you say to those patients?

Sam Yates (23:32)
think I always try and remind people just that we're waiting, but it doesn't mean we're not doing anything while we are. We're not deferring treatment because we don't want to get started. We are collecting.

Mary (23:38)
Right.

Sam Yates (23:46)
very eagerly and aggressively collecting as much information both about the patient and about the disease as we can. And I will go ahead and jump to one of the important conclusions of the studies. We're not saying that you should wait as long as possible to treat a patient. We're saying that you definitely should have next generation sequencing results, mutational profile, and you should evaluate a patient's fitness, their comorbidities their performance status, and things that you find, you should try and optimize those as best as possible before starting treatment. yeah, what I try and tell patients is, historically, we didn't have as many drugs as we do now. So that's one part, and we have a lot of treatment. We have a lot of decisions to make these days in terms of what we would want to use. And being able to make those decisions requires having this information.

And so we are going to get that information as quickly as we can and keep you as healthy as possible and oftentimes improve your health actually in those days while we're waiting to start treatment. And then once we're all ready, we will move forward with treatment. I think, you know, it's also a little counterintuitive, but I find, you know, I saw a patient earlier this week who oftentimes patients have things that are coming up that they're just like, wow, it sounds really great that I don't have to go into the hospital right now to start treatment for this aggressive disease. I think patients feel a lot of relief and that ease when their physician walks in and this physician doesn't have this look of dismay on their face. And they're like, no, we're going to take our time here.

We're going to be very deliberate and do our due diligence to make sure we

Mary (25:13)
Yeah.

Sam Yates (25:41)
leave no stone unturned. And then when we're all ready to move forward, then we will move forward. There are certainly certain circumstances where patients are very, very ill. And we do have to say, you know what, I'm sorry, but today we need to admit you into the hospital and we need to get started. But I would say those are few and far between.

Mary (26:01)
I think that's a good way to help reframe it maybe for someone whose initial reaction is to feel uncomfortable with that idea, to reframe it as this is giving them the chance to go home, digest the information, talk to their loved one, maybe tie up some loose ends with people that you had something scheduled for next week and you can talk to that person instead of that initial.

Sam Yates (26:18)
Mm-hmm. Mm-hmm.

Mary (26:28)
huge whirlwind that has been seen in AML in the past. I think that's a great way to look at it. And then also something you mentioned, the patient being able to see other physicians to help with other comorbidities that they may be experiencing. Who is leading that? Is the patient now scheduling all of these doctor's appointments? How does that process go after, say they have these other things?

Sam Yates (26:35)
Mm-hmm.

Yeah, definitely not.

Yeah, yeah, I think, you know, we, I'm at the University of Chicago, you know, we, and I did my residency here as well, which is very convenient. You start to get to know all the other departments because you rotate through so

Mary (27:04)
Yeah.

Sam Yates (27:06)
I think many folks either in private practice or in an academic setting will have their colleagues in pulmonology or cardiology or endocrinology. You know, if someone has very poorly controlled diabetes saying, you know, hey, unfortunately, this gentleman has a new diagnosis of cumulonil leukemia. I want to start this regimen that may impact their diabetes. Could you see them tomorrow and get them, you know, get them a little bit better controlled or certainly from a cardiology perspective, cardiology, we work with them very closely and there's a wonderful new, I would say field emerging of cardio-oncology and we're fortunate to have some cardio-oncologists here at the University of Chicago and many centers have these now. It's wonderful, yeah, and they know a lot more about the heart than I do. So it's really wonderful when you can call those folks and say, I would really appreciate if you could see them tomorrow and almost always the answer is yes.

Mary (27:49)
That's amazing.

Sam Yates (28:04)
and getting that optimization done before we start, think can really make an impact. And I will say that the data on optimization strategies or what we kind of call pre-habilitation strategies for patients with AML are, there's not a lot of literature out there, but there's papers probably in the next year or so that will be coming out showing that some of these models do work. we've published on some of this work in patients undergoing allogeneic stem cell transplant, and then also in CAR T cell therapy, which is more relevant to lymphoid leukemias, but in myeloma and lymphoma, but there's emerging data that these pre-habilitation models can improve patients' outcomes by basically getting them healthier before they start their therapy.

Mary (28:53)
It's really exciting and cool to see the increase of more specialized help for these patients across the board to address their health concerns. What does it look like for say a patient knows that they have a heart condition and they have a doctor? Is the coordination between doctors beginning?

Is the patient needing to initiate that?

Sam Yates (29:15)
Yeah, we try and initiate that. think there's so much going on for these patients when they initially get diagnosed. Certainly if they're like, you know what, I'm fine with communicating with them. We're not going to say no, but we always try and facilitate those conversations. And if it's someone within our own institution, that's very, very easy. we have patients who come from all over the Midwest, sometimes across the country. And it's easy to make a phone call to those folks.

You know, say, hey, we're this patient, think that their platelets are, we know their platelets are gonna drop quite a lot. They're on this anti-coragulation for such and such heart condition. You know, can we come to a decision together on what's our game plan for managing this to make sure that their heart function stays okay, but we can also get a good outcome from the leukemia treatment as well.

Mary (30:08)
I'm sure that collaboration is not only like we just talked about, beneficial to the patient's overall outcome, but the collaboration is beneficial for the patient and their own mental wellbeing, knowing that it's being handled.

Sam Yates (30:21)
Yeah, absolutely. I would never want the burden of that communication to fall on the patient. And we also, you I think all oncology practices try and have nurse navigators who are just critically important primary nurses, nurse practitioners. Oftentimes when it's medication decisions as well, our oncology pharmacists are really phenomenal. So it's having a large multidisciplinary team can make a huge difference because the care of patients with AML is very complex. It's a hard disease to treat and the medicines can have side effects. So having a big team is a huge benefit.

Mary (31:05)
So what does this information mean for patients moving forward with AML? What does this mean for their survival?

Sam Yates (31:16)
I think what it means, number one, is that when patients realize they have find out that they have a new diagnosis of AML and when they are going in to see their oncologist, or maybe they've just gotten out of that initial visit, it's helpful to know that there is published data out there to say that it is okay and is actually helpful to wait for this genetic testing to come back and to basically optimize their health as much as possible before starting therapy. And I think that will have an impact, this data will have an impact on oncologists as well. I think this study got chosen for the highlights of Ashtore throughout North America. And I think it got chosen because it has very important real world impact for...you know, an oncologist in private practice where they can say, oh, it actually is probably beneficial to wait, even though it's more than likely that they're going to get a hypomethylating agent in the benidoclax. It's important to double check that and make sure that there's nothing that we may find on next generation sequencing that may inform their treatment decision. And also in the meantime, while I'm waiting for that, let's go ahead and get a heart ultrasound. Let's take a look at the lungs. Make sure that there's nothing that we could improve on there before starting. So I think it gives peace of mind both to providers and to patients.

Mary (32:49)
How does this information, this data that we've gotten from this research, how does this change potential treatment guidelines for AML?

Sam Yates (32:58)
Yeah, that's a, that is a big question. will say guidelines changing from, you know, even very large retrospective studies can be hard to do. And there will always be disagreement and discussion about potential biases in retrospective research, which I completely agree with. And in the paper that we're probably going to publish pretty soon, we try and, you know, allude to those limitations and acknowledge them for sure.

With that being said, I think that at the very least, and I think in the coming years, it will be considered standard of care to await the mutational profile of a patient's AML. Again, that next generation sequencing test. And especially as these tests get faster and faster and faster, it's not gonna be as much of an ask up to say waiting for two weeks. But I would say in our practice, the vast majority of providers, if not all of them, they await the brief version of that next generation sequencing test, because we also do a broader one as well, which most institutions do. the one that has the FLIT3, the IDH1, IDH2, the TP53, we really want to know that information. I think within guidelines, it will become standard that it will be recommended that we wait for that before starting treatment.

Mary (34:20)
So where do you go from here? What is next? if you got to decide where research went in this area, what would that look like?

Sam Yates (34:29)
Yeah, so as I alluded to before, so my focus is on fitness assessments and I primarily focus on older adults with AML and my learning dependencies in general. So there are a number of approaches to fitness assessment and there's no standard of care yet. I was mentored by Heidi Kleppen who's a really  well-known geriatric oncologist at Wake Forest, who is one of the pioneers of something called a geriatric assessment, which the concept, which I think your listeners will be familiar with and agree with, is the idea that if you have two patients who are 68 years old, just because they're 68, they're not the same people. They may be very, very different in terms of the comorbidities that they have

Mary (35:14)
Right?

Sam Yates (35:19)
How physically active they are, what jobs do they do, and those sorts of things. And that information, as we've seen over the past more than a decade now, is very informative in terms of determining what treatment a patient may get. going from just getting that information and seeing how it predicts how well a patient may survive is one thing, and that's what we've done up to this point. There are studies now looking at the ability of actually using that information at the time of diagnosis to help decide along with the mutational profile of that patient's AML what treatment to give them. And so rather than just using the pretty basic tests that we do right now in clinical trials, using what's called a comprehensive geriatric assessment to restratify patients of how fit they are and have that guide the treatment that we give, which is going to be, I think, increasingly important as we get more and more therapies and is also very helpful, I will say, in our practice in determining whether a patient should get an intensive regimen or a less intensive regimen. So that's where my research focuses and ongoing data that we'll be releasing probably at ASH in 2025 and years moving forward.

Mary (36:33)
That's exciting. And I think it's a field that patients are going to be really interested in because it directly impacts their treatment. And it's something that they can see the results of and it affects the whole group of patients versus just a specific mutation or something like that. So I think this is definitely something to keep their eye on.

Sam Yates (36:43)
Uh-huh.

Yeah.

And the large impetus, for me, this idea came back in 2019 when I realized we didn't have data on time from diagnosis to treatment in HMA-Ven with the idea being that I want to do pre-habilitation trials. I want to do interventional trials where we're optimizing patient's health before they start their AML therapy. But as you can imagine, that takes time. And so you need to show that you, what is the approximate

Mary (37:19)
Yeah.

Sam Yates (37:24)
amount of time that we can wait before starting therapy. And I think this information is helpful to justify people who are doing predibilitation trials. And thankfully there's multiple people across the country who's really interested in this type of work. So I think the field will increasingly move in this direction in the coming years.

Mary (37:45)
Very exciting, we'll definitely keep an eye and watch and see what goes next. with all of this information, all of this data, all of this potential changes for how AML standard of care would be, what advice do you have for newly diagnosed patients based on all of this information?

Sam Yates (38:04)
Yeah, I think number one is do not be shocked or alarmed if, you know, it goes back to something you said earlier, patients come into that first visit and they've often, you know, used Google or whatever search engine and they see this as an aggressive disease and they want understandably to be rid of this thing as quickly as possible, which we do too, 100%. But I really think that

taking our time and making sure we know four things. I always tell people four things that we really wanna know. We wanna know the disease biology. So I wanna know the mutations, the chromosomal changes. I wanna know the treatment options that I have. I wanna know what type of social support a patient has, because sometimes that can be really, really important. And then I wanna know host fitness. So those four things I really wanna know. And getting really good quality information about those four things and then making a treatment decision can take some time. I think it's helpful for patients to know that don't be alarmed if your provider is saying, we're gonna wait for this information and then we're gonna come together and we're gonna make a treatment plan together and then move forward together based off that information. Not to be alarmed, but actually to be comforted that we're gonna be doing our due diligence, make sure we get good information and then move forward.

Mary (39:31)
I think it's a good problem to have in the AML space for current information to differ from what patients are seeing a lot online. There are so many new treatments, so much new research that's come out within the last couple of years, like you mentioned earlier, and this new data that suggests maybe wait and see what all this information comes back. That way you can make a more informed decision on how to treat with the patient and the doctor and all of the other doctors that might be involved in that patient's care with other fitness things like you mentioned earlier. I think it's a good problem to have that there's more decisions to be made now.

Sam Yates (40:02)
Mm-hmm.

Yeah, and we're, we always try and remind people we are going to wait for this information, but we are always a phone call away. You we're always available. And we give very, very strict return precautions of if this happens, you need to call us immediately. And at that point, we would bring into the hospital. So we want people to enjoy, you know, their life at home as much as possible while we're awaiting that information before often we initiate therapy in the hospital. And I think that's really nice for patients too. They get that initial visit, which can be just a tsunami of information and they get to go home and process that with their family members, their loved ones, their dogs, cats, and then prepare mentally as well for a hospital stay.

Mary (40:42)
Yeah.

Sam Yates (40:56)
It's hard to measure the impact that that has on patients' outcomes, but I certainly think that that makes a difference.

Mary (41:02)
Well, thank you so much for being willing to come on today and to share your research and for the research that you're doing and the interest you have in this specific area of care for AML patients. And we will excitedly be watching to see what comes next. And we'd love to have you back on if there's ever more information or new information to share.

Sam Yates (41:22)
Yeah, absolutely. Thank you so much for having me.

Mary (41:28)
Okay, so many pieces of amazing information shared in this episode. I think one of my main takeaways is the importance of getting the right testing done upfront when possible so that treatments and decisions about care can be as tailored to each individual as possible. I am so excited about the direction we're going in AML research related to how providers are making decisions with the help of genetic testing that helps to ensure that patients are getting the best care possible to manage their AML.

If you wanna keep learning about treatments and decision-making in AML, I have two resources I'd encourage you to look into. First is our Health Tree University Program, specifically our Know Your Therapy units and our unit on testing and genetics. This Health Tree University Program, if you're not familiar, shares information in a short video format with top experts explaining these complex topics in easy-to-understand ways. Another source I suggest is a podcast episode we did with Dr. Joshua Zeidner late last year that is a full overview of Menin Inhibitors and Dr. Zeidner's trial on Menin Inhibitors. These new drugs, Menin Inhibitors, are the newest drugs in the AML space and are actually really exciting and can possibly change the way AML is treated. So if you want to keep learning, look into those resources. If they piqued your interest, I'll link them in the episode description so you can check them out. I want to thank you for joining us on today's episode of the Health Tree Podcast for AML. I hope you learned something new.

Join us next week where we're gonna talk with Dr. Emily Hsieh about the complexities and challenges of treating pediatric AML, as well as some of her exciting research into CAR T therapy for this unique AML population. I think this episode is going to be really exciting for the pediatric population, but not only them. I think a lot of the insights that she shares and some of this work in CAR T is gonna be relatable to all AML patients. So I encourage you to tune in. I would love to hear your thoughts on today's episode. Share them with me in a comment on whatever platform you're listening or send them to me in an email. You'll also be able to find my email in the episode description. Until next time!