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Expert Overview | AML Treatment Options and Phases of Therapy |
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Transcript:
Katherine Banwell:
Hello and welcome, I’m your host Katherine Banwell. Thanks for joining us for another webinar in the Patient Empowerment Network’s Elevate Series. The goal of these programs is to help AML patients and care partners feel educated and informed when making decisions with their healthcare team.
Before we get into the discussion, please remember that program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Daniel Pollyea. Welcome. Thank you so much for being with us. Would you introduce yourself?
Dr. Daniel Pollyea:
Yes, thanks so much for having me. I’m Dan Pollyea and I work at the University of Colorado where I lead the leukemia team.
Katherine Banwell:
Thank you so much for joining us today. As part of this new series we’re learning more about researchers like you. You’re on the frontlines of advancing AML care. What led you here and why is it important to you?
Dr. Daniel Pollyea:
I think my path is everyone’s, is distinct and a bit different.
In short, I think working in AML is one of the most exciting areas in medicine that a person can be in right now. It’s this incredible intersection between delivering potentially curative treatments to patients and sort of harnessing the most unbelievable research-driven sort of drug development, new therapies to patients. So, it’s just a really, really exciting time for all of us who work in the AML field because of all that those opportunities bring to bear.
Katherine Banwell:
Let’s start by having you define AML for the audience.
Dr. Daniel Pollyea:
AML, acute myeloid leukemia, it’s a type of a cancer. You can think of it as a cancer of the bone marrow, and it’s the likely result of several abnormalities, or sometimes I call them mistakes that can occur in stem cells or a stem cell in the bone marrow. And those mistakes that occur, most times, we don’t understand why they happen.
In most cases, they’re completely out of a person’s control. This isn’t something that comes on because it runs in a family in most cases, or because of something somebody did or didn’t do. These appear to be pretty random events that occur. But these mutations that occur in these sort of stem cells in the bone marrow cause a cell to become a cancer cell.
And over a course of a variable amount of time, these can evolve and develop into this condition, AML.
Katherine Banwell:
Okay, thank you for that. Health literacy, which is defined by the ability to find, understand, and use information for health-related decisions, is essential. Would you expand on the term “health literacy” and why it’s important to accessing quality AML care?
Dr. Daniel Pollyea:
Yeah. So, I think health literacy in our field is a challenge, because these are acute conditions that come on oftentimes very quickly. And these are not diseases that are top of mind. Most people don’t know somebody who’s had this. They’re not common; only about 30,000 people every year in the United States will have AML. So, it’s very hard to have any sort of background in this.
And for most patients because of the pace at which this disease occurs, it can be very difficult to sort of read up on it before meeting with a provider or an expert or a specialist. So, there’s a lot of challenges or barriers to health literacy. But like anything, the more a person knows, the more sort of empowered they can be, the more ability they have to ask questions and seek care at sort of the optimal place.
What I find often is that health literacy is best harnessed by a patient’s team; so, in other words, their support system, their family and friends. Because it’s so much to deal with in such rapid succession, to get this diagnosis and to usually be feeling very poorly. To also be expected to sort of have read the most relevant literature and come armed with that information is often too much at the beginning.
So, in the beginning, I think it’s best to leave that to your support system, and then as time goes on and as you start treatment, get comfortable, health literacy in our field, it becomes a more prevalent issue. And I think that when patients learn the most about how the field has evolved and where we are, the better that they can potentially do.
Katherine Banwell:
Well, that leads us perfectly into my next question. What resources do you suggest for boosting knowledge about AML?
Dr. Daniel Pollyea:
AML is like so many fields in medicine, but probably more so, moving so quickly that sort of the usual Google search is not going to, in most cases, bring up the most important, the most relevant information.
So, I think that there are some organizations out there that do a really good job of educating patients. The Leukemia & Lymphoma Society is one. They have a good website.
They have people you can contact, and they have really good information that’s available to patients and their families. That’s where I typically recommend people start. And then from there, based on our interest in education level and things like that, there can be other resources. But I think The Leukemia & Lymphoma Society’s a great place to start.
Katherine Banwell:
Okay. Newly diagnosed patients and their care partners are often overwhelmed, as you mentioned earlier. What advice do you give them at their first appointment?
Dr. Daniel Pollyea:
Right. So, this is a huge challenge. Anybody in the situation would be feeling like this. So, first of all, it’s sort of like, it’s okay to feel like this. It’s normal.
It would be unnatural to not be overwhelmed with what you’re going through; that’s an important message. And then, I think there’s this period of time between diagnosis and a plan that is particularly anxiety-provoking. And so, as your doctor and their team sort of sorts through the necessary information to get a plan together, just know that that this a very anxiety-provoking time when you’re being told that you have a really significant and serious disease, and we don’t have a plan yet.
So, making sure that you sort of comfort yourself during that period, knowing that that his temporary and that is potentially the worst anxiety you will feel, I think, can be helpful. And then, from there once the plan is sort of in place and enacting it, it really is just focusing on short-term goals.
So, instead of thinking three steps ahead and how’s the transplant going to work, in the early days, focusing on “Okay, how am I going to get into a remission?” and “How am I going to feel day-to-day? How can I feel as best I can day-to-day? What’s the best path to a remission?” And then, once you sort of meet the goal of remission, “Okay, what’s next? How are we going to cure this?” So, thinking through sort of in short bites, I think, is best.
Katherine Banwell:
Are there other key questions that they should be asking their doctor or their healthcare team?
Dr. Daniel Pollyea:
Yeah. Depending on the situation, this is a disease that can be cured; and so, from the first day, asking “Is that a possibility for me? Is there a curative plan for me, and what might that look like?” I think is an important question to ask from the beginning.
Making sure you communicate your goals and your wishes, how you define quality of life, what that means to you. And in that way, that can really help inform your doctor and their team to put together a plan that sort of is most customized to you.
Katherine Banwell:
That makes sense. Excuse me. When it comes to choosing AML therapy, it’s important to work with your healthcare team to identify what will be best for you. Would you walk us through the factors that are considered when choosing therapy for AML?
Dr. Daniel Pollyea:
Sure, yeah. So, we now have options in treatments for this disease and for decades, that wasn’t the case. This was a one-size-fits-all type of disease. And in the last eight years, that has completely changed.
So, there are approaches and diagnosis that vary between very intensive chemotherapy and less intensive treatments. What we call “targeted therapies” in some cases can be considered or be appropriate.
And so, having a sense, after learning a little bit about this, of how much would you be willing to tolerate an intensive chemotherapy regimen and all the risks inherent in that, if that’s even being presented as an option, and if so, what does that look like? And if not, hey, what are the other options if that sort of doesn’t sound like something that you would be willing to accept? So, I think those kind of probing questions.
First, asking yourself and then sort of translating that into your treatment team, into “Hey, this is sort of how I define quality of life.
And these are some red lines that I wouldn’t cross,” that can really help the healthcare team because, again, this is not one-size-fits-all anymore. We do have several options to consider at the time of diagnosis.
Katherine Banwell:
What other factors would you take into consideration? Do you look at age and overall health and fitness, test results?
Dr. Daniel Pollyea:
Absolutely. So, the relevant factors at the time of diagnosis would be, as you described, age, to some extent. And there’s no magic cutoff. “When a person is a certain age, this is no longer a treatment.” But age just gives us guidelines. Other comorbidities, other disease that you may be dealing with, things in your past, organ dysfunction; all those things are really, highly considered.
And also, sort of your own attitude toward “Hey, would I be okay with a month-long stay in the hospital or is that something that there’s no sort of outcome that that would be okay for me to withstand?” But then, the other huge part of this are things that are sort of, at diagnosis, unknown to you and unknown to your doctor for a little bit. And those are disease factors. So, what are the mutations that make up your disease? What’s making your disease tick? And now, just with normal clinical care, we have unbelievable access to this information. We can essentially learn within a week or two every relevant mutation that’s contributing to your disease.
And that helps us tremendously with respect to prognostication, sure, but also treatment selection because there are some treatments that will work, we think, better with certain disease biology, and other treatments that will work less well.
And we even have targeted therapies; so, based on particular mutations or other abnormalities, sort of a rationally designed therapy for exactly that disease biology. So, that is also a huge part of treatment selection, and we call those disease factors.
Katherine Banwell:
Why is molecular testing important following an AML diagnosis?
Dr. Daniel Pollyea:
Right. So, this basically just gets into what we were just discussing. So, that molecular testing is the testing that will tell us all the mutations that make up your disease biology. And so, that is crucial for prognostication, but also treatment selection.
And frankly, also when thinking about how to potentially cure your disease, those will be factors taken into account to make decisions that are pretty significant, such as should you receive a bone marrow transplant at some point in the future or not. And the reason it’s so crucial to get this done at diagnosis is, after diagnosis, we start a treatment, and hopefully we put your disease into a remission.
And at that point, we no longer have access to your disease cells. They’re gone, or they’re too low to even measure. And so, we need to get this information at diagnosis so that we can have it later on so that we can really understand your disease and make the best treatment plan for you.
Katherine Banwell:
Right. We’ve covered this in past programs, but I think it’s worth reiterating. Would you define induction and consolidation therapy for the audience?
Dr. Daniel Pollyea:
Yeah. So, traditionally when we only had intensive chemotherapy treatments, induction meant “Let’s get your disease under control.” That’s the first sort of line of treatment. “Let’s induce a remission.” That’s where that comes from.
And then, consolidation meant “Let’s do more stuff, more chemotherapy to consolidate that remission,” or you can think of it as maintain that remission, deepen that remission. All those are sort of the same adjectives there. So, induction was step one. Consolidation was step two. We’ve retained a lot of this language into a time when we don’t only have intensive chemotherapy. So, we’ll still use the word induction sometimes to mean “Let’s get your disease under control, even if it’s not with intensive chemotherapy.” So, admittedly that can be very confusing, but if someone uses it in that manner, that what they’re talking about is “Let’s get your disease under control.”
And consolidation still meant “Let’s deepen your remission” or “Let’s prolong your remission.” So, those are the general terms. They’re very much linked to intensive chemotherapy, which we still use, but it’s not all we use anymore.
So, I think it has gotten confusing, and it’s perfectly reasonable to be confused about that terminology.
Katherine Banwell:
Would you share an overview of the types of therapy for AML, and how do you decide which patient gets what?
Dr. Daniel Pollyea:
Yeah. Because things are very different at relapse too, but at diagnosis, the options still are intensive chemotherapy, which is a regimen that hasn’t changed much in several decades really, 50 years.
And then, there are other treatments. There’s a treatment called venetoclax (Venclexta) that we pair with a low-intensity chemotherapy treatment, either azacitidine (Vidaza), decitabine (Dacogen), or something called low-dose cytarabine (Cytosar U). Those are the three sort of partners for venetoclax.
And then, there’s a targeted therapy against leukemia cells that have an IDH1 mutation that’s called ivosidenib (Tibsovo) that we also give with low-dose chemotherapy. So, in most cases those are the sort of three general options. That last treatment that’s targeted against IDH1, we typically preserve that for older patients or those that really are not good candidates for intensive chemotherapy but who have that IDH1 mutation, which is only somewhere around 10 percent of AML patients.
And then, so then the main decision then is “Do we give intensive chemotherapy, or do we give the venetoclax regimen?” And our policy is sort of, if we think we can cure you within intensive chemotherapy, and there’s certain disease biology subtypes that can be cured potentially with intensive chemotherapy, then that would be our first choice for you.
If we don’t think we can cure you with intensive chemotherapy, if you don’t have that disease biology or if you do but you’re just not a candidate for that type of an approach, that’s when we give the venetoclax regimen.
Katherine Banwell:
Are there other targeted therapies that you use?
Dr. Daniel Pollyea:
Yes. So, venetoclax is a targeted therapy against Bcl-2. Unlike some of these other gene mutations, you don’t have to have something; there’s no mutation in Bcl-2 that you need to be a candidate for venetoclax. We give venetoclax pretty much to any potential AML patients. Genomically-targeted therapies: you mentioned FLT3. Before I mentioned IDH1. There’s also one for IDH2. We hope there’s a couple more of these coming. Where these are approved, for the most part, at the moment, are in the relapse setting.
So, a patient who r