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AML Gene Mutations | Emerging Targeted Therapies in Development

 

What are emerging targeted therapies for AML? Dr. Daniel Pollyea discusses the current landscape of targeted treatments for AML gene mutations, while emphasizing ongoing research efforts surrounding less common mutations.

Dr. Daniel Pollyea is Clinical Director of Leukemia Services in the Division of Medical Oncology, Hematologic Malignancies and Blood and Marrow Transplant at University of Colorado Cancer Center. Learn more about Dr. Pollyea.
 
 
Related Resources:
AML Therapy | Emerging Treatments and Clinical Trials

AML Therapy | Emerging Treatments and Clinical Trials

An Overview of Current AML Treatment Types

An Overview of Current AML Treatment Types

AML Treatment Planning | Key Questions to Ask You Doctor

AML Treatment Planning | Key Questions to Ask You Doctor

Transcript: 

Katherine Banwell:

Chris sent in this question: I would like to hear more about mutations found during molecular testing. Are there new AML drugs in trials for other less common mutations? 

Dr. Daniel Pollyea:

Great question. So, at the moment, what we have clinically available are targeted therapies for patients with FLT3 mutations, IDH1, and IDH2 mutations.  

And there are about 50 different genes that can be mutated in AML, and so that’s a small slice of the pie. Those are relatively common mutations, but still, small slice of the pie. A lot of the very uncommon or less common gene mutations we don’t have great paths to targeted therapies for them.  

And is that just we never will? I don’t think necessarily, but I think those can be really challenging. Not every mutation is amenable to a targeted therapy, at least as far as we know now. The one that’s coming, that we’re hopeful about is NPM1, which may be able to be targeted with one of those menin inhibitors that we talked about. So, that’s the next big one up.  

And that will probably constitute 40 percent of patients that have one of those mutations that I listed. But research is ongoing to kind of try and dig into this more. What I will say is that the AML research community is so fantastic that every lead is being pursued, and there is a lab somewhere in the world whose focus is on whatever small, even the most least common AML mutation; that’s somebody’s focus. 

And so, if there were to be promising therapies developed for even rare mutations, I assure you, the field would take those forward and figure out a way to do those clinical trials and to get to approval if it’s appropriate. So, but I think that’s where the landscape is right now.   

AML Treatment Planning | Key Questions to Ask Your Doctor

 
What key questions should patients ask about their AML treatment plan? Dr. Daniel Pollyea provides key advice and emphasizes the importance of sharing symptoms, while also highlighting the critical role of a care partner for support and advocacy in AML care.
 
Dr. Daniel Pollyea is Clinical Director of Leukemia Services in the Division of Medical Oncology, Hematologic Malignancies and Blood and Marrow Transplant at University of Colorado Cancer Center. Learn more about Dr. Pollyea.
 
 

Related Resources:

How Is an AML Treatment Plan Determine?

How Is an AML Treatment Plan Determined?

AML Treatment | Understanding Induction and Consolidation Therapy

AML Treatment | Understanding Induction and Consolidation Therapy

An Overview of Current AML Treatment Types

An Overview of Current AML Treatment Types

Transcript: 

Katherine Banwell:

Dr. Pollyea, when choosing a therapy what questions should patients be asking their healthcare team about a treatment plan? 

Dr. Daniel Pollyea:

So, at the time of diagnosis I think it’s a reasonable question to say, “Is my disease amenable to a cure? Can I be potentially cured?” and “Is this treatment part of a plan for a cure?” If that is possible, then I would want to be walked through the steps that that’s going to executed. And if it’s not possible for me to be cured, then I would like to discuss what is the treatment plan that could potentially give me the longest duration of a remission and the best quality of life. And so, that’s the conversation that I think is important to have.  

And then, everything that we discuss comes into play there; an individual’s sort of appropriateness for intensive chemotherapy versus less intensive regimens, and also the disease biology and what that maybe make them a candidate for.  

Katherine Banwell:

Are there certain symptoms or side effects a patient should share with their care team?  

Dr. Daniel Pollyea:

Yeah. So, we have a very, very sort liberal request that really anything, it should be shared. We have a 24/7 number to call with one of us on-call at all times. So, it’s very difficult for a patient to kind of be able to appreciate, when they’re going through such dramatic changes, “Hey, is this expected or not?” So, we really emphasize oversharing concerns about symptoms.  

All these drugs have very different side effect profiles, and some of them are common and some of them are less common. The disease itself can cause symptoms and clinical issues. So, instead of really trying to educate yourself in an impossible way on what could be or is not related, it’s better just to ask.  

Katherine Banwell:

What is the role of a care partner when someone is in active treatment? 

Dr. Daniel Pollyea:

Having a care partner is crucial. This is physically and mentally extraordinarily stressful on the body and on the mind. Having that support person for those purposes is really important. Having that person be an advocate for a patient to ask those questions that may not be getting asked, to reframe questions to get the best answers is really, really important.  

And then, there’s the more mundane things; just getting patients to their appointments and kind of keeping their morale up and those things. So, there’s data and research on this that patients with caregivers, they have better outcomes. When it comes to a transplant, a caregiver is not an option. You must have a caregiver. And the importance of that will be sort of relayed to you in the context of a discussion about a transplant. But a caregiver in the setting of a transplant is so important that it is a requirement to even be considered for that.   

An Overview of Current AML Treatment Types

 

Dr. Daniel Pollyea provides an overview of AML treatment options, explaining the choices between intensive chemotherapy and targeted therapies, while also discussing when stem cell transplants are considered.
 
Dr. Daniel Pollyea is Clinical Director of Leukemia Services in the Division of Medical Oncology, Hematologic Malignancies and Blood and Marrow Transplant at University of Colorado Cancer Center. Learn more about Dr. Pollyea.
 

 

Related Resources:

AML Therapy | Emerging Treatments and Clinical Trials

AML Therapy | Emerging Treatments and Clinical Trials

AML Gene Mutations | Emerging Targeted Therapies in Development

AML Gene Mutations | Emerging Targeted Therapies in Development

AML Treatment Planning | Key Questions to Ask You Doctor

AML Treatment Planning | Key Questions to Ask You Doctor

Transcript: 

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 receives a treatment, and then either doesn’t respond or responds and then relapses, that’s typically where we bring in these genomically-targeted therapies. There’s an exception for IDH1 that, like I said, can be used now in the upfront treatment setting. But for the most part, these genomically-targeted therapies are relevant in relapse disease. 

Katherine Banwell:

When would you use stem cell transplant?  

Dr. Daniel Pollyea:

So, stem cell transplant for the majority of AML patients is still the only potential way to cure this disease. And so, a stem cell transplant is something that we give for that purpose. It’s something that we really reserve for people whose disease is in a remission. So, nobody comes in at diagnosis and goes right into a stem cell transplant; that wouldn’t work. So, you first have to achieve a remission with any number of one of the combinations of things that we’ve already discussed.  

But once the patient is in a remission and doesn’t have a curative strategy with, like, intensive chemotherapy or some other approach and is a good candidate for a transplant, which is a whole other sort of set of circumstances that has to be considered, that’s patients who we offer a transplant for. 

AML Therapy | Emerging Treatments and Clinical Trials

 
What new AML treatments are emerging? Dr. Daniel Pollyea discusses recent advances in AML therapy, including the new menin inhibitors in development, and which patients they may be right for. Dr. Pollyea also emphasizes the crucial role of clinical trials as a treatment option for patients. 
 
Dr. Daniel Pollyea is Clinical Director of Leukemia Services in the Division of Medical Oncology, Hematologic Malignancies and Blood and Marrow Transplant at University of Colorado Cancer Center. Learn more about Dr. Pollyea.
 

 

Related Resources:

AML Gene Mutations | Emerging Targeted Therapies in Development

AML Gene Mutations | Emerging Targeted Therapies in Development

An Overview of Current AML Treatment Types

An Overview of Current AML Treatment Types

AML Treatment Planning | Key Questions to Ask You Doctor

AML Treatment Planning | Key Questions to Ask You Doctor

Transcript: 

Katherine Banwell:

What about new and emerging treatments?  

Dr. Daniel Pollyea:

So much that’s really exciting here. So, we’ve had several new approvals. We have a new FLT3 inhibitor that we can use for newly diagnosed patients who have a FLT3 mutation and who are getting intensive chemotherapy.  

We have, even now, a new therapy that’s given as a maintenance treatment. It’s called oral azacitidine or Onureg, which is really exciting as well.  

But I think the next sort of big thing in the field is going to be a targeted therapy for another subset of patients who are defined by the presence of a gene mutation, NPM1, but also by a chromosomal abnormality, something we call KMT2A. But these patients have disease that’s potentially amenable to what we call a menin inhibitor.

And there are several companies with menin inhibitors. These therapies are getting pretty far along. We expect approval potentially soon for at least one of them. And then, I think these are going  to have a big impact on the field for those patients who have that type of disease. 

Katherine Banwell:

Oh, that’s exciting news. Where do clinical trials fit in? 

Dr. Daniel Pollyea:

So, clinical trials are crucial for everything that we’re trying to do. We don’t make any progress without clinical trials. So, that’s the field as a whole. We don’t move forward. We don’t get any of these new treatments without clinical trials.  

On an individual patient level, clinical trials are also really important because, for many patients we are still not doing as well as we want to be doing with this disease. We’ve made progress, but there’s still a lot of room for improvement. And so, for an individual patient, getting access to another therapy that, although we admit we don’t quite know yet whether it may be helpful but might be helpful, I think, is a really compelling situation to potentially consider participating because it is a guarantee you will help the field; and it’s a guarantee you will help every patient that comes after you through participation in clinical trial.  

But all these clinical trials are also designed to help you; to help you in a situation where we as a field don’t feel like we’re doing well enough. So, clinical trials, totally crucial if we’re going to continue making progress.  

And clinical trials are the reason why these last 10 years we have had such just dramatic improvement in availably of all these new therapies because literally thousands of patients have chosen to participate. 

Katherine Banwell:

How can patients find clinical trials that might be right for them? 

Dr. Daniel Pollyea:

So, back to The Leukemia & Lymphoma Society. They can be really helpful in guiding this. Asking your doctor, “Hey, are there any clinical trials her or at any other center that I should be considering?” And then, people who are interested in just going to the source. Every clinical trial that is available is registered at clinicaltrials.gov. And so, going to clinicaltrials.gov and then putting in some keywords like “acute myeloid leukemia,” you’ll see every clinical trial that’s available. 

How Is an AML Treatment Plan Determined?

 

Dr. Daniel Pollyea explains the importance of collaborating with your healthcare team on your AML care decisions and discusses factors that guide an individualized AML treatment plan, such as age, overall health, and personal preference. Dr. Pollyea also addresses the role of common AML gene mutations when choosing therapy.

Dr. Daniel Pollyea is Clinical Director of Leukemia Services in the Division of Medical Oncology, Hematologic Malignancies and Blood and Marrow Transplant at University of Colorado Cancer Center. Learn more about Dr. Pollyea.
 

 

Related Resources:

AML Treatment | Understanding Induction and Consolidation Therapy

AML Treatment | Understanding Induction and Consolidation Therapy

An Overview of Current AML Treatment Types

An Overview of Current AML Treatment Types

AML Treatment Planning | Key Questions to Ask You Doctor

AML Treatment Planning | Key Questions to Ask You Doctor

Transcript: 

Katherine Banwell:

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.  

Elevate | Expert Advice for Accessing Quality AML Care and Treatment

 
How can you access the best care and treatment for YOUR AML? Dr. Daniel Pollyea, an AML expert, discusses the importance of patient education, including understanding the available treatment options for AML, how test results may impact care, and he shares advice for advocating for yourself.
 
Dr. Daniel Pollyea is Clinical Director of Leukemia Services in the Division of Medical Oncology, Hematologic Malignancies and Blood and Marrow Transplant at University of Colorado Cancer Center. Learn more about Dr. Pollyea.
 

Related Resources:

Choosing Therapy | How Are AML Treatment Goals Determined?

Choosing Therapy | How Are AML Treatment Goals Determined?

Expert Overview | AML Treatment Options and Phases of Therapy

Expert Overview | AML Treatment Options and Phases of Therapy

What Are AML Inhibitor Therapies and How Do They Work? 

What Are AML Inhibitor Therapies and How Do They Work?

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 receives a treatment, and then either doesn’t respond or responds and then relapses, that’s typically where we bring in these genomically-targeted therapies. There’s an exception for IDH1 that, like I said, can be used now in the upfront treatment setting. But for the most part, these genomically-targeted therapies are relevant in relapse disease. 

Katherine Banwell:

When would you use stem cell transplant?  

Dr. Daniel Pollyea:

So, stem cell transplant for the majority of AML patients is still the only potential way to cure this disease. And so, a stem cell transplant is something that we give for that purpose. It’s something that we really reserve for people whose disease is in a remission. So, nobody comes in at diagnosis and goes right into a stem cell transplant; that wouldn’t work. So, you first have to achieve a remission with any number of one of the combinations of things that we’ve already discussed.  

But once the patient is in a remission and doesn’t have a curative strategy with, like, intensive chemotherapy or some other approach and is a good candidate for a transplant, which is a whole other sort of set of circumstances that has to be considered, that’s patients who we offer a transplant for. 

Katherine Banwell:

Okay. What about new and emerging treatments?  

Dr. Daniel Pollyea:

So much that’s really exciting here. So, we’ve had several new approvals. We have a new FLT3 inhibitor that we can use for newly diagnosed patients who have a FLT3 mutation and who are getting intensive chemotherapy. We have, even now, a new therapy that’s given as a maintenance treatment. It’s called oral azacitidine or Onureg, which is really exciting as well.  

But I think the next sort of big thing in the field is going to be a targeted therapy for another subset of patients who are defined by the presence of a gene mutation, NPM1, but also by a chromosomal abnormality, something we call KMT2A. But these patients have disease that’s potentially amenable to what we call a menin inhibitor. And there are several companies with menin inhibitors. These therapies are getting pretty far along. We expect approval potentially soon for at least one of them. And then, I think these are going  to have a big impact on the field for those patients who have that type of disease.

Katherine Banwell:

Oh, that’s exciting news. Where do clinical trials fit in? 

Dr. Daniel Pollyea:

So, clinical trials are crucial for everything that we’re trying to do. We don’t make any progress without clinical trials. So, that’s the field as a whole. We don’t move forward. We don’t get any of these new treatments without clinical trials 

On an individual patient level, clinical trials are also really important because, for many patients we are still not doing as well as we want to be doing with this disease. We’ve made progress, but there’s still a lot of room for improvement. And so, for an individual patient, getting access to another therapy that, although we admit we don’t quite know yet whether it may be helpful but might be helpful, I think, is a really compelling situation to potentially consider participating because it is a guarantee you will help the field; and it’s a guarantee you will help every patient that comes after you through participation in clinical trial.  

But all these clinical trials are also designed to help you; to help you in a situation where we as a field don’t feel like we’re doing well enough. So, clinical trials, totally crucial if we’re going to continue making progress.  

And clinical trials are the reason why these last 10 years we have had such just dramatic improvement in availably of all these new therapies because literally thousands of patients have chosen to participate. 

Katherine Banwell:

How can patients find clinical trials that might be right for them? 

Dr. Daniel Pollyea:

So, back to The Leukemia & Lymphoma Society. They can be really helpful in guiding this. Asking your doctor, “Hey, are there any clinical trials her or at any other center that I should be considering?” And then, people who are interested in just going to the source. Every clinical trial that is available is registered at clinicaltrials.gov. And so, going to clinicaltrials.gov and then putting in some keywords like “acute myeloid leukemia,” you’ll see every clinical trial that’s available.  

Katherine Banwell:

Oh, that’s excellent. I’d also like to add for our viewers that if you’re interested in learning more about AML care and treatment, PEN has a number of resources available to you.  

You can find these at powerfulpatients.org/AML or by scanning the QR code on your screen.  

So, Dr. Pollyea, when choosing a therapy what questions should patients be asking their healthcare team about a treatment plan? 

Dr. Daniel Pollyea:

So, at the time of diagnosis I think it’s a reasonable question to say, “Is my disease amenable to a cure? Can I be potentially cured?” and “Is this treatment part of a plan for a cure?” If that is possible, then I would want to be walked through the steps that that’s going to executed. And if it’s not possible for me to be cured, then I would like to discuss what is the treatment plan that could potentially give me the longest duration of a remission and the best quality of life. And so, that’s the conversation that I think is important to have.  

And then, everything that we discuss comes into play there; an individual’s sort of appropriateness for intensive chemotherapy versus less intensive regimens, and also the disease biology and what that maybe make them a candidate for.  

Katherine Banwell:

Are there certain symptoms or side effects a patient should share with their care team? 

Dr. Daniel Pollyea:

Yeah. So, we have a very, very sort liberal request that really anything, it should be shared. We have a 24/7 number to call with one of us on-call at all times. So, it’s very difficult for a patient to kind of be able to appreciate, when they’re going through such dramatic changes, “Hey, is this expected or not?” So, we really emphasize oversharing concerns about symptoms.  

All these drugs have very different side effect profiles, and some of them are common and some of them are less common. The disease itself can cause symptoms and clinical issues. So, instead of really trying to educate yourself in an impossible way on what could be or is not related, it’s better just to ask.  

Katherine Banwell:

What is the role of a care partner when someone is in active treatment? 

Dr. Daniel Pollyea:

Having a care partner is crucial. This is physically and mentally extraordinarily stressful on the body and on the mind. Having that support person for those purposes is really important. Having that person be an advocate for a patient to ask those questions that may not be getting asked, to reframe questions to get the best answers is really, really important.  

And then, there’s the more mundane things; just getting patients to their appointments and kind of keeping their morale up and those things. So, there’s data and research on this that patients with caregivers, they have better outcomes. When it comes to a transplant, a caregiver is not an option. You must have a caregiver. And the importance of that will be sort of relayed to you in the context of a discussion about a transplant. But a caregiver in the setting of a transplant is so important that it is a requirement to even be considered for that.  

Katherine Banwell:

Sounds like that’s vital. I’d like to get to a few audience questions that we received before the program. Chris sent in this question: I would like to hear more about mutations found during molecular testing. Are there new AML drugs in trials for other less common mutations? 

Dr. Daniel Pollyea:

Great question. So, at the moment, what we have clinically available are targeted therapies for patients with FLT3 mutations, IDH1, and IDH2 mutations.  

And there are about 50 different genes that can be mutated in AML, and so that’s a small slice of the pie. Those are relatively common mutations, but still, small slice of the pie. A lot of the very uncommon or less common gene mutations we don’t have great paths to targeted therapies for them. And is that just we never will? I don’t think necessarily, but I think those can be really challenging. Not every mutation is amenable to a targeted therapy, at least as far as we know now. The one that’s coming, that we’re hopeful about is NPM1, which may be able to be targeted with one of those menin inhibitors that we talked about. So, that’s the next big one up.  

And that will probably constitute 40 percent of patients that have one of those mutations that I listed. But research is ongoing to kind of try and dig into this more. What I will say is that the AML research community is so fantastic that every lead is being pursued, and there is a lab somewhere in the world whose focus is on whatever small, even the most least common AML mutation; that’s somebody’s focus. 

And so, if there were to be promising therapies developed for even rare mutations, I assure you, the field would take those forward and figure out a way to do those clinical trials and to get to approval if it’s appropriate. So, but I think that’s where the landscape is right now. 

Katherine Banwell:

This question comes from Rita: Outside of changes in bloodwork, what are signs that AML is returning? 

Dr. Daniel Pollyea:

Great question.  

So, this can be a really tough one, and bloodwork is what we sorta hang our hat on. There are some times that patients sort of have clinical symptoms that proceed changes in bloodwork. I will say, I find that to be pretty uncommon. But some of the things that are pretty rare but might happen, would be leukemic involvement of the skin; so, it would appear as a rash. Some people might have some fatigue that comes on before the blood counts really change. That’s also pretty rare.

And then, if this disease were to work its way into any other organ or tissue in the body, and that’s rare, it’s possible that that could present with clinical signs and symptoms before a blood count change. But for the most part, the blood counts are really early sign that something is changing, and typically we’ll see that before any clinical signs.   

Katherine Banwell:

Thank you for that, Dr. Pollyea, and those were great questions. Please continue to send them to question@powerfulpatients.org, and we’ll work to get them answered on future programs. So, as we close out the program, Dr. Pollyea, what would you like to leave the audience with? Why are you hopeful that about the future of AML care and treatment?  

Dr. Daniel Pollyea:

Well, we’ve made unbelievable progress in just the last 10 years. And so, just looking into the future, I see nothing stopping that progress. So, it’s really exciting to think about where we’ll be two, five, 10 years from now. We never could have envisioned 10 years ago where we are now in terms of the therapies we have, how active and effective they are, and the impact that it’s had on patients.  

Again, just so proud to be part of this community, both on the patient care side and on the research side. It’s such a committed group of people, working around the clock on this disease to figure it out and to make some improvements. For all those reasons, I’m just super hopeful that we’ll just keep making progress, and I see no signs of anything slowing down. 

Katherine Banwell:

That’s a promising outlook to leave our audience with. Dr. Pollyea, thank you so much for joining us today. 

Dr. Daniel Pollyea:

Thanks so much for having me. 

Katherine Banwell:

And thank you to all of our collaborators. To learn more about AML and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today.  

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Equitable Access: Overcoming Challenges in Precision Medicine for Veterans with Lung Cancer

Equitable Access: Overcoming Challenges in Precision Medicine for Veterans with Lung Cancer from Patient Empowerment Network on Vimeo.

Do veterans with lung cancer face barriers to precision medicine and targeted therapies? Expert Dr. Michael Kelley from Duke University School of Medicine discusses past and current access to precision medicine, the National Precision Oncology Program, and proactive patient advice to ensure you receive essential testing and optimal care.

[ACT]IVATION TIP

“…if you have advanced lung cancer, ask your provider, what testing has been done on my tumor, what are the results, and what does that mean for my treatment?”

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Navigating Lung Cancer Clinical Trials: VA Support and Resources for Veterans

Transcript:

Lisa Hatfield:

Dr. Kelley, what specific challenges do veterans face in accessing precision medicine? And how can these challenges be mitigated to ensure equitable access to advanced treatments?

Dr. Michael Kelley:

So before 2016, the first cancer moonshot, there were major challenges in, not only in the VA, but across the country to access to precision medicine in the oncology field. We launched in that year, and if really now provide access to cutting-edge precision oncology technology, which is a lot of molecular testing and the expertise to be able to interpret the results of that test to apply it to individual patients. So I think we have advanced to the point where this should not be a barrier anywhere in the VA system, but I would say that only about half of veterans are enrolled for VA care.

And outside of VA there still are areas that have a variety of different barriers to getting the testing done on the tumor samples in a way which informs the treatment decision-making for patients. So this is very important. My activation tip for this is to be sure to ask your provider whether your tumor has been tested for molecular tests, and if so, what the results of those tests are, and how that impacts the treatment of your cancer.

Lisa Hatfield:

Dr. Kelley, can you speak to your research around barriers to prescribing targeted therapies for patients with non-small cell lung cancer with highly actionable gene variants, and what should patients and their care partners be aware of related to these barriers?

Dr. Michael Kelley:

So one of the key pieces of information that your providers need to know in order to, how to treat your advanced stage lung cancer is what are the molecular alterations in your tumor, and what types of proteins are expressed on the surface of the proteins that allows them to make good choices around immune therapy and another group of therapies called targeted therapies, and that can make major differences in your care and your outcome.

So when we first started using this type of testing, in particular the genetic testing of tumor samples, there was a lot of complexity in the results that was not well understood by the oncology providers, because it was new and very complex. So VA has instituted a program to provide that testing and the expert consultation service to be able to interpret those results.

And so when we set up that program, which is called the National Precision Oncology Program, we did a study, looking to see how many patients who should have gotten a targeted drug actually got that drug. And the results were similar to what has been reported in other healthcare systems. And that is, is that less than every patient was getting the targeted therapy, and it was about somewhere around a third of patients who did not get the therapy that would’ve been indicated by that test result.

So we wanted to know what the reasons were, and I think we’ve addressed a lot of the reasons that we came upon. A lot of it is education and making sure that the information from those tests gets to the provider and gets to the patient, and that comes with an understanding of what those test results mean. So my activation tip is, if you have advanced lung cancer, ask your provider, what testing has been done on my tumor, what are the results, and what does that mean for my treatment?


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Empowered by Biomarker Testing: Amber’s Journey with Stage IV NSCLC

Empowered by Biomarker Testing: Amber’s Journey with Stage IV NSCLC from Patient Empowerment Network on Vimeo.

Amber, a 56-year-old living with stage IV non-small cell lung cancer (NSCLC), shares her journey of empowerment through biomarker testing and targeted therapy. From recognizing symptoms and proactive healthcare to managing her condition with the latest treatments, Amber’s story emphasizes the importance of personalized care and staying informed. Her advocacy for biomarker testing and clinical trials aims to inspire others facing similar challenges to take an activated approach in their lung cancer care.

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Transcript:

Embracing an activated approach to non-small cell lung cancer (NSCLC) care is indispensable for every patient. My name is Amber, I am 56 years old and living with non-small cell lung cancer. Recognizing the importance of proactive healthcare and being in good physical condition, I sought medical attention upon experiencing troubling symptoms. 

I was 54 when I started experiencing symptoms of coughing, wheezing, and decreased stamina. I worked as a nurse practitioner and knew lung cancer can happen to anyone with lungs. After getting a CT scan, they discovered a spot on my lung and swollen lymph nodes in my chest. A PET scan and brain scan came next to help determine my diagnosis.

I was shocked to learn I had stage IV lung cancer that spread. My oncologist knew about the latest in biomarker testing and immediately scheduled it, which determined I was EGFR-positive. Even though that sounded frightening, I learned there was targeted therapy that worked well for EGFR-positive patients.  

I’ve been on this EGFR blocker since my diagnosis. My tumor is no longer visible, and my lesions have decreased considerably. I’m monitored regularly and stay active hiking and spending time with my family. I’m so thankful biomarker testing enabled my care team to prescribe targeted therapy. It’s a huge advancement in lung cancer care. And if you’re a former smoker and are unsure when to start lung cancer screening, ask your doctor. Even if you smoked many years ago, you should continue to receive lung scans. 

I hope that sharing my story will help other patients understand the importance of biomarker testing. 

Here are my activation tips:

  1. Ask your care team questions to learn about biomarker testing, treatment options, and what to expect during and after treatment.
  2. Don’t allow stigmas to keep you from getting the best personalized lung cancer care.
  3. Ask if a clinical trial may be a potential treatment option for your type of lung cancer.

Remember, no matter who you are and what kind of health history you have, being proactive is everything. Stay activated by being informed, empowered, and engaged in your lung cancer care.


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What Are AML Inhibitor Therapies and How Do They Work?

What Are AML Inhibitor Therapies and How Do They Work? from Patient Empowerment Network on Vimeo.

What are AML inhibitor therapies, and how do they work? Dr. Gail Roboz explains the different types of inhibitor therapies, their targets, the patient type they may benefit most, and a new class of targeted treatments.

Dr. Gail Roboz is director of the Clinical and Translational Leukemia Programs and professor of medicine at Weill Cornell Medicine and the New York Presbyterian Hospital. Learn more about Dr. Roboz.
 

 

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Transcript: 

Katherine Banwell:

You mentioned one inhibitor as targeted therapy, but there are a couple of others. Would you briefly tell us about those? 

Dr. Gail Roboz:

So, over the years recently, we have identified certain specific targets in AML which are resulting in the addition of medications on these standard backbones. So, the target for venetoclax (Venclexta) is something called BCL2, and actually, venetoclax probably makes all chemotherapy better. It’s kind of a controversial statement, but I’m going to stand by it. But in AML, it has been shown that the addition of venetoclax to lots of different backbones makes them work better. There are other things to hit, though.  

For example, there are patients with AML who have something called a FLT3, F-L-T-3 mutation. This mutation also has specific inhibitors that are FDA-approved drugs that target specifically the FLT3 mutation, and if you have one of those, your doctor may add on a FLT3 inhibitor to either a lower intensity or an intensive backbone. Similarly, there are agents called IDH inhibitors. There are IDH1 and IDH2 inhibitors. 

If I start getting into isocitrate dehydrogenase pathways on this webinar, I think everybody will click off, because it’s certainly bored all of the medical students in med school, and it’s pretty tough to understand. But the bottom line is it’s very cool stuff because that boring pathway in medical school that nobody really thought about too much is actually part of very, very, central cellular functions that are a vulnerability now that have been identified in leukemic cells that, if you hit them with these specific inhibitors, patients do better.  

Now, couple of things for patients. It doesn’t mean that it’s better to have a FLT3 or an IDH mutation because the targeted therapies are available. So, a lot of patients are disappointed when they don’t have mutations. I don’t want you to think in that way. It’s not that it’s better, it’s different.  

It identifies a different biology. If you have certain mutations, there are certain medications that may help you more.  

That’s why I think the patients are learning quickly, too, to ask the doc – they may not remember the letters of the alphabet soup, but “Do I have something about my AML that can get one of these targeted therapies added on?” I think is a good question to think about. “Do I have something about my disease that has a specific drug that we’ve already learned makes outcomes better?”  

Katherine Banwell:

There’s a new emerging therapy as well. Is it the menin inhibitor? 

Dr. Gail Roboz:

I think that, in understanding different targets and different pathways, it leads me to a general statement that if you can get yourself potentially onto a clinical trial at an academic center, that is something to consider right out of the gate. Because there is a lot, a lot, a lot going on in this field right now. 

What we are hoping, and the reason that I am talking to you about venetoclax and FLT3 inhibitors and IDH inhibitors, is because of all the patients who jumped onto those clinical trials and proved that those drugs are better. Some of them are my patients! I was fortunate on some of those early trials to have some real winners in patients who got onto the trials. They’re the ones who drove the success. 

So, for example, menin inhibitors, which are very, very exciting, targeted agents for NPM1 and KMT2A mutations and rearrangements – these are complicated to remember as a patient, but there’s a cool drug out there that might be for you.  

I think that patients who really think about asking the question wherever they are, the “Hey, I just got a diagnosis of AML. Is there a clinical trial that might look good for me?” I think is a great question to ask pretty much out of the gate. 

Expert Overview | AML Treatment Options and Phases of Therapy

Expert Overview | AML Treatment Options and Phases of Therapy from Patient Empowerment Network on Vimeo.

What are the treatment options and phases of therapy for AML? Dr. Gail Roboz discusses the various therapies available to treat AML and to maintain remission, the timing of these therapies, and novel treatment approaches offered. 

Dr. Gail Roboz is director of the Clinical and Translational Leukemia Programs and professor of medicine at Weill Cornell Medicine and the New York Presbyterian Hospital. Learn more about Dr. Roboz.
 

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What Are AML Inhibitor Therapies and How Do They Work?

Transcript: 

Katherine Banwell:

Dr. Roboz, would you provide a brief explanation of the phases of therapy for AML?  

Dr. Gail Roboz:

Yeah. So, here, too, I have to say that it’s more confusing than it used to be for the following reasons. So, historically and currently, we typically talk about induction as the first therapy that you’re going to get to get into remission. 

Then, the treatment paradigm is you do something to get into remission; do some treatment to get into remission. After that, in the realm of post-remission therapy, there are different things that can happen. There can be something called consolidation, which might be another round of chemotherapy. Some patients get consolidation, some patients don’t. After consolidation, there can be a transplant.  

So, you get into remission, you may or may not get a little bit of what’s called consolidation chemotherapy, and then go on to a transplant. 

However, sometimes either after the transplant or after chemotherapy before ever getting or instead of ever getting a transplant, there might be ongoing treatment in a lower intensity ongoing basis that is called maintenance.  

So, you’ve got to think about it as induction as what happens first, consolidation is something that happens when you’re in remission, and then maintenance usually refers to ongoing therapy that is different from consolidation. 

It’s usually lower intensity, easier to take, oral types of treatment that may go on and on. And just to be incredibly confusing, it’s different from something like breast cancer, where often the patients are given, “You get six cycles of this, and then you’re done.” From AML, there’s actually often not that type of an obvious plan right out of the gate for the patient. 

The answer will be, “It depends.” It depends. It depends how your treatment looks at this point in time. It depends how you look at this point in time. 

So then, the patients say, “Well, aren’t you going to cure me of this? What are you doing? Aren’t you going to get rid of it?” So, historically, there are some patients who get cured with chemotherapy. They get chemotherapy to get into remission, they get some chemotherapy afterwards, and there’s a cure rate for some patients with that. The majority of patients who are cured with AML get an allotransplant, or a transplant from somebody else. 

Then there’s a whole group of patients where we’re asking the question now, is it possible to get those patients beyond five years – so in oncology, five years is typically defined as cure. Can we get some patients with ongoing therapy to that past-five-year mark without a transplant? That’s in the zone of the ‘coming soon.’ Don’t have a ton of patients in that group right now, but hopefully we will. 

Katherine Banwell:

You’ve mentioned some various treatment types that are used to treat AML. Can you share a brief overview of available treatments? 

Dr. Gail Roboz:

So, the terminology that we use is a little bit annoying, because it is a little bit general. We say intensive and not intensive. 

But historically, intensive chemotherapy referred to a combination of generally two types of agents, cytarabine (Cytosar-U) and an anthracycline, which is a class of chemotherapy, that either just those two together or in combination with sometimes a third or a fourth drug usually keeps people in the hospital for around a month. Not that the chemotherapy takes that long, but the treatment gets rid of basically a lot of cells in the bone marrow, good guys and bad guys, and it takes about three weeks for those normal cells to recover. 

So, a standard intensive induction for AML is often around three to four weeks in the hospital, somewhere between three and five or so days of chemotherapy up front, depending on exactly what the protocol is. The classic regimen is actually still called 3+7, three days of one drug, seven of the other. But there are many variations of that that work. 

The chemo is then stopped, the patient hangs out in the hospital, very frequently getting transfusions and antibiotics, and we wait for the bone marrow to recover.  

Another current path that many patients are getting – almost all older patients, with ‘older’ being defined not by a specific age cutoff, but often 75 and older, almost everybody agrees no longer gets the classic chemotherapy that I just described. At some institutions, that 75 is going down, and even 70 and 65 and above are getting a new type of therapy, mostly because the new type of therapy is working pretty well. That is a combination of something called a hypomethylating agent.  

Drugs like azacitidine (Vidaza, Onureg) or decitabine (Dacogen) in combination with a pill that has changed the landscape of AML more than any other called venetoclax (Venclexta). Venetoclax is a drug that is not exclusively used for AML. 

It actually was originally approved for another type of leukemia. But I think that not many people would argue with the statement that what has changed absolutely the face of AML treatment has been this drug, because it’s a BCL2 inhibitor. What it does is it actually – cancer cells and leukemia cells in particular are very, very good at staying alive.  

They don’t undergo cell death, they don’t want to die, and venetoclax brings down their forcefield so that those cells can actually undergo apoptosis and die. 

Venetoclax in combination with azacitidine or decitabine has transformed the care of the disease, because many patients older than 65 – and the median age of diagnosis of AML is around 68 to 70. So, many patients never were well enough to have the intensive therapy. They weren’t going into remission, and they weren’t having prolonged survival often beyond a few months. 

But now, those patients do actually much better with the combination of aza [azacitidine] and venetoclax. So typically, the induction path is going to be deciding who gets an intensive therapy backbone, usually associated with long hospitalization. Who gets a less intensive backbone – by the way, that is often associated with just the same hospitalization. So, that’s why I don’t love the term ‘low intensity,’ because that implies that it doesn’t work.  

It does, and it also implies that you’re not going to be in the hospital. You probably will, because in the same way as for the more so-called intensive therapies, getting into remission involves getting rid of bone marrow cells and waiting for the normal ones to recover. Even if you are a patient who is getting the venetoclax combined with the azacitidine or decitabine, which is typically called low intensity, you may very well be in the hospital for a month. 

Because depending on where you live and who your family is and how sick you might be, you will probably want us to watch you carefully during that first month, but it’s worth it. Because if you have a good chance of getting into remission, remission is what makes life better and life longer. So, we want to get patients into remission, even if it means upfront time in the hospital. 

What Key Testing Occurs Following an AML Diagnosis?

What Key Testing Occurs Following an AML Diagnosis? from Patient Empowerment Network on Vimeo.

What key tests occur following an AML diagnosis? Dr. Gail Roboz explains the procedures and tests to confirm the diagnosis, assess disease risk, examine AML genetic markers, and develop a treatment plan.

Dr. Gail Roboz is director of the Clinical and Translational Leukemia Programs and professor of medicine at Weill Cornell Medicine and the New York Presbyterian Hospital. Learn more about Dr. Roboz.
 

Related Resources:

Choosing Therapy | How Are AML Treatment Goals Determined?

Choosing Therapy | How Are AML Treatment Goals Determined?

Expert Overview | AML Treatment Options and Phases of Therapy

Expert Overview | AML Treatment Options and Phases of Therapy

What Are AML Inhibitor Therapies and How Do They Work? 

What Are AML Inhibitor Therapies and How Do They Work?

Transcript: 

Dr. Gail Roboz:

We often generally recommend a bone marrow biopsy, even if we know we can make the diagnosis from a blood test, because even though the bone marrow biopsy is not the most fun test in the world, it does offer better information for follow-up care than what you can get initially from the blood. 

So, every once in a while, we do have a patient for whom a bone marrow biopsy itself for whatever reason can’t be done. But almost always, we need a bone marrow biopsy, and on that biopsy, you’re going to look under the microscope and see what the cells look like. You’re going to get back standard testing, which is called flow cytometry, which is going to tell the difference between what are the different cells that you’re seeing under the microscope. 

But then you’re actually going to get progressively much more fancy testing, including things called chromosomes or cytogenetics, and then ultimately, the majority of patients, if at all possible, will be having mutational testing to identify certain subgroups of AML that benefit from very particular treatments. Next-generation sequencing, PCR, fusion proteins, FISH, cytogenetics, I can go on and on with all kinds of terminology that is very confusing, even to hematology fellows, let alone to patients.  

Usually, we use a combination of tests to decide, “Is this patient likely to be able to be cured with chemotherapy alone, or might this patient benefit from a stem cell transplant from somebody else after they go into remission?” 

That’s basically what the prognostic scoring systems used to be asking, but now it’s a lot more complicated than that. Because even in the favorable categories, even in the adverse categories, where there used to be very little subtlety, now there is a lot of subtlety. 

It’s all about defining getting into remission, and what do I give you once you’re in remission to keep you there? It’s no longer this windshield wiper thing of good, bad, transplant, no transplant. There’s a lot more to AML than there used to be.   

Choosing Therapy | How Are AML Treatment Goals Determined?

Choosing Therapy | How Are AML Treatment Goals Determined? from Patient Empowerment Network on Vimeo.

How are AML treatment goals determined? Dr. Gail Roboz explains the collaborative decision-making process between patients and clinicians when exploring treatment options, important questions to ask about AML treatment goals, and the objectives of the first phase of treatment.

Dr. Gail Roboz is director of the Clinical and Translational Leukemia Programs and professor of medicine at Weill Cornell Medicine and the New York Presbyterian Hospital. Learn more about Dr. Roboz.
 

 

Related Resources:

What Key Testing Occurs Following an AML Diagnosis?

What Key Testing Occurs Following an AML Diagnosis?

Expert Overview | AML Treatment Options and Phases of Therapy

Expert Overview | AML Treatment Options and Phases of Therapy

What Are AML Inhibitor Therapies and How Do They Work? 

What Are AML Inhibitor Therapies and How Do They Work?

Transcript: 

Katherine Banwell:

When it comes to choosing therapy for AML, it’s important to work with your healthcare team to identify what will work best for you, the patient. So, I’d like to know how you define shared decision-making.  

Dr. Gail Roboz:

The problem with AML sometimes is that it can be such an acute, emergency-type of presentation and urgent decision-making that I think your question is almost right out of the gate for some patients that will, “Wait, I don’t even have a minute, here. How do I build a team, do the research, look online if people are telling me that I’m in the middle of an emergency?”  

That isn’t always the case for acute leukemia, but it sometimes is. I think that what happens in AML in particular for patients is a building of knowledge and a building of the team, and figuring out, first of all, where am I when I am being told this diagnosis, and is it really an emergency? Do I have to make decisions really right now, because is it life-threatening today, I don’t have time to look around? Or do I have a minute to pause and get more information? 

I definitely feel that with the Internet era and with so much connection between doctors and teams, there is much more ability to reach out instantaneously for doctors, too, to get advice on a patient who might be in a smaller hospital that doesn’t have AML experience. But I think that the first thing is to try to figure out very, very quickly, what needs to happen to me as a patient immediately, and what can wait a minute, so that I can figure out what am I being told, and what are my options? 

Katherine Banwell:

Right, right. It can be confusing for patients, just finding out this new information. Part of making care decisions is setting goals. What are AML treatment goals, and how are they determined?   

Dr. Gail Roboz:

I would say that leaving cure on the table from the beginning is always a good place to start, because you want to figure out, first of all, what am I dealing with? What are the actual options?  

But when AML strikes, and a patient who has multiple medical conditions or comorbidities that are truly compromising function independently of the diagnosis of AML, that’s going to be a special path of what is actually reasonable for someone who is terribly medically ill or otherwise frail right from the beginning? That can be defining goals, but I think from the beginning, the best thing is to leave everything on the table. What can actually be done to make me better, first of all, to get me out of my immediate trouble? What can be done to make me better, and if I’m getting better, well, I like that, how do I stay there?  

What can be done to hang on to the state of ‘better,’ which is sometimes defined as remission? In AML, the goal is to get the bone marrow working again, functioning again, get rid of the acute emergency problem, if there is one, which there may or may not be in acute leukemia. 

Sometimes it’s truly an emergency, and sometimes it isn’t. But once I get better, can I stay there? What is required to keep me with a working bone marrow for as long as possible?  

But once you are starting to sort through the diagnosis, you realize that saying that somebody has acute myeloid leukemia is not telling me nearly enough information. This is a disease that is what we call biologically heterogeneous, which means there are lots of different forms. It’s like saying you’re sick. What exactly does that mean? There are lots of things that can make you sick. There are lots of different subtypes of AML, and fairly quickly in most institutions, we start getting back some information specifically on the subtype and biological characteristics of the disease.  

This can be very, very important in the initial treatment planning, and depending on where you are, the information that you get back can sometimes take 24 hours, 48 hours, 72 hours, a week. So, you start learning very quickly though that, “If I’m not in a complete emergency that requires instantaneous treatment, can I get back more information about the biological subtype of the disease so that I can start treatment planning of what is my best option right out of the gate?” That’s usually called induction, or the first therapy that you’re going to get with the goal, ‘getting rid of leukemia cells and getting into remission.’ That’s part one, and then everything that comes after that is about keeping you in remission.   

But for the initial goal, what is the therapy that the patient needs to get to get into remission? In order to figure that out, the good news is there are a lot of different ways to slice and dice getting into remission, and actually, it used to be such a weighty decision. 

Now, I would actually encourage people to – not relax, you can never use the word ‘relax’ with acute leukemia. But there are several different induction strategies for most patients that would be okay.  

So, even if you get started with one strategy and you hear five days later that another doctor might do something different, there are a lot of ways to safely get into remission. I think everybody should be pleased about the fact that we’re doing much better than we used to for patients across the board, all the way from children to much older adults, to safely getting people into remission. 

Katherine Banwell:

So, what sort of factors then do you take into consideration when you’re choosing a therapy? 

Dr. Gail Roboz:

So, out of the gate, there are the patients that I think I referred to earlier who truly, truly are in situations based on their other diseases that there are certain treatments we would just cross out right out of the gate. 

If there are patients with very, very severely compromised cardiac or renal or lung function or are terribly ill from other conditions, AML doctors will right out of the gate for those patients eliminate certain treatments. But absent that scenario, what we try to look for is the biology of the disease. Not look at the age, not look at the comorbidities unless they are so severe that they make obvious certain choices. 

But rather, what I like to do is say, “What kind of AML is this, and what is the best treatment that I have to get this patient into remission?” And then ask the question, “can this particular patient handle this therapy?” Sometimes, these days, there actually may be more than one route to get to remission depending on the biology of the disease, and then, if that’s the case, then I can start getting picky and look at the individual patient. Where does the patient live? Who’s the patient’s family? What other diseases has the patient been treated for?  

Is there something that I can use? If I have a choice, if there are a couple of different things that might work, how do I fit the treatment to best take care of the needs of this particular patient? If I don’t have choices, then my question is, “Okay, how do I get this patient through my one therapy that I think is the truly, truly best option?” 

Advanced Non-Melanoma Skin Cancer | Establishing a Treatment Plan

Advanced Non-Melanoma Skin Cancer | Establishing a Treatment Plan from Patient Empowerment Network on Vimeo.

What advanced non-melanoma skin cancer therapies might comprise a treatment plan? Dr. Soo Park discusses therapy types, the impact of molecular testing, and shares key questions to ask about your treatment plan.

Dr. Soo Park is a Medical Oncologist at Moores Cancer Center at UC San Diego Health. Learn more about Dr. Park.

Download Resource Guide

 

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Advanced Non-Melanoma Skin Cancer Test Results | Understanding YOUR Disease

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Advice for Accessing Advanced Non-Melanoma Skin Cancer Clinical Trials


Transcript:

Katherine:

So, what is the typical treatment path for someone who’s been diagnosed at this stage of disease, at the advanced stage?  

Dr. Park:

Yeah, so, before – and I really love this question, because in the past, we did not have that much to offer patients except surgery, and then they would get a very extensive surgery. They would get reconstruction. But sometimes it’s hard to get reconstruction after a really major surgery, because you have to heal, and you have to get better. And then, after the surgery, you would typically get radiation to try to prevent the cancer from coming back. But nowadays, we have immune therapy.  

So, immune therapy is a certain type of IV medicine that’s not chemotherapy that works really well for squamous cell skin cancer. And so, nowadays, we can actually give this to you before surgery. So, we can give you a couple of doses of this IV immune therapy medicine before surgery, and really shrink your tumor quite dramatically.  

And then, that makes the surgery a lot easier, smaller. And then, sometimes after we do the surgery, and then we look at what the surgeon has taken out under the microscope, we can’t see any tumor left. And that’s really amazing, because then sometimes we don’t even need to do radiation. So, not only did we make your tumor a lot smaller, sometimes we completely made it go away.   

And then, if that happens, sometimes we don’t even need to do radiation. So, it really helps the patient. And I think this is really important, because this is somewhat newer data, and I still see patients that get referred to me for just surgery. 

But I think a lot of head and neck surgeons are now aware of this data. And so, this is something that’s, I think, becoming more common.  

Katherine:

What about targeted therapies?  

Dr. Park:

So, targeted therapies are, I think, mainly used in basal cell skin cancer. So, targeted therapies are typically oral medications or pills. They’re called targeted, because they’re used in cancers that have a specific target. So, for example, the basal cell skin cancer, the target is the hedgehog pathway, because the hedgehog pathway is abnormal. And so, these pills, they specifically target the hedgehog pathway. But for squamous cell skin cancer, we don’t have any true targeted therapies.  

Katherine:

As patients are reviewing their options with their doctor, what questions should they be asking about their care plan? 

Dr. Park:

I think all patients should be asking, what the goal of the treatment is. They should be asking, especially if they’re being offered any type of treatment, what are the side effects? What can I expect from this, in terms of how much better will it make me? They should really ask about how often the treatments are given, because some patients have transportation issues or financial barriers, and we want to know about that, so we can help them.   

Patients should also ask about any necessary blood work that is needed. They should ask what can they do in the future to prevent a similar type of cancer happening, and just make sure that they’re talking to their families, because I think social support is really important.  

Katherine:

Yeah. I think it’s important for patients to ask how the cancer is going to impact their lives overall, really.  

Dr. Park:

Yeah, exactly, because it will affect every single aspect of your life: your social life, your family life, your mental health, your physical well-being. And so, it’s really important to know and work with your doctor on what you think you can expect now, and also in the future.  

Katherine:

Yeah. Well, how do test results impact treatment options, then? 

Dr. Park:

So, there are sometimes when we have a skin cancer that actually happens inside a gland in your face. It’s one of the salivary glands in your face. And we sometimes don’t know if it’s a skin cancer that happened on the outside and that spread to the gland inside your face, or did it actually first just start inside the gland? Because a cancer that just starts inside the gland is not technically a skin cancer. It’s a different type of head-and-neck cancer, and it’s very, very rare, and it’s treated very differently.  

So, nowadays, because we have that molecular testing, like I talked about, I see lots of patients where they have a cancer in their salivary or parotid gland. We don’t know where it came from. And so, we send it for molecular sequencing or molecular testing, and there are certain clues in the molecular testing that can tell us, oh, it probably actually came from a skin cancer.  

You just didn’t know it; or maybe it’s the skin cancer that kind of was there and went away; or maybe it was a skin cancer you had like five years ago, that you didn’t think caused any problems, but it did spread, because knowing where it came from through molecular sequencing, if it’s really hard to find out where, really impacts the treatment I may give you. 

Katherine:

What about side effects of these therapies? How are they managed?  

Dr. Park:

Yeah, so, for immunotherapy, there’s one specific side effect that we don’t find with chemotherapy, and that’s really when your body’s own immune system kind of ends up attacking the other parts of your body. And so, it can cause inflammation of other organs. And so, for patients that experience that, it can be very mild, and it can be all the way to very severe, requiring a patient to go to the hospital.  

But in all cases, we just have to tell the immune system to quiet down a bit, because it’s attacking your body. And so, the way we do that is we give the patient steroids. And so, if it’s really mild, maybe you have like a small rash; maybe we can just give you a steroid cream, or maybe we have to give you a steroid pill. But sometimes, if it’s really severe, we have to tell you to go to the hospital so you can get steroids through your IV.