Tag Archive for: mutation
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.
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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.
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.
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AML Gene Mutations | Emerging Targeted Therapies in Development |
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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.
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AML Gene Mutations | Emerging Targeted Therapies in Development |
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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 |
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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.
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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 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.
Follicular Lymphoma Patient Expert Q&A: Dr. Brad Kahl
Dr. Brad Kahl from Washington University School of Medicine explores the transformative potential of emerging therapies for follicular lymphoma and their significance for patients and families. He also addresses the unique challenges of living with follicular lymphoma and its impact on patients’ lives today.
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Transcript:
Lisa Hatfield:
Welcome to this START HERE Patient Empowerment Network program. This program bridges the expert and patient voice, enabling patients and care partners to feel comfortable asking questions of their health care team. Joining me today is hematologist-oncologist Dr. Brad Kahl, Professor of Medicine in the Division of Oncology at the Washington University School of Medicine and Director of the lymphoma program at the Alvin J. Siteman Cancer Center in St. Louis, Missouri. Thank you so much for joining us, Dr. Kahl.
Dr. Brad Kahl:
It’s a pleasure. Thanks for having me, Lisa.
Lisa Hatfield:
The world is complicated, but understanding your follicular lymphoma diagnosis and treatment options along your journey doesn’t have to be. The goal of Start Here is to create actionable pathways for getting the most out of your follicular lymphoma treatment and survivorship. No matter where you are on your journey, this program is designed to provide easy to understand, reliable, and digestible information to help you make informed decisions. And most of all, we’re asking questions from you. I’m thrilled you’ve joined us.
Please remember to download the program resource guide via the QR code. There is great information there that will be useful during this program and after. Let’s start here. Dr. Kahl, there is a great deal going on in the follicular lymphoma landscape, and I want to dig into that. But before we do, as is custom for this program, I’d like to start with a brief overview of this disease. What is follicular lymphoma? And can you break it down a little bit, the key differences between Hodgkin and non-Hodgkin lymphoma and how follicular lymphoma fits into that?
Dr. Brad Kahl:
Sure. The terminology can be kind of confusing to patients, so I’ll try to explain it. Hodgkin lymphoma is a specific kind of lymphoma. Non-Hodgkin’s lymphoma just means it’s not Hodgkin’s. So non-Hodgkin’s lymphoma is just a big, broad, descriptive term. It’s like saying automobile. But there are lots of different kinds of cars, obviously. So follicular lymphoma is a specific type of non-Hodgkin’s lymphoma. So it’d be like saying Chevy Malibu or something specific within that automobile term. So there’s like 100 different kinds of non-Hodgkin lymphoma. Follicular lymphoma is one of those. A
nd it’s kind of a unique answer biologically and clinically. Follicular lymphoma is characterized by this particular mutation inside the cells that sends a signal to the cells that says don’t die. So instead of being a disease of rapid cellular proliferation and growth, it’s more of a disease of slow cellular accumulation. If people can picture that, the cells are just accumulating slowly. So it’s kind of a slow-moving cancer. And probably when patients are diagnosed, they’ve probably had it for a long time already.
They just didn’t know it, because follicular lymphoma often doesn’t cause symptoms. And usually when we get a patient with newly diagnosed follicular lymphoma, the disease is very widespread. And that obviously makes people fearful. And so we spend a lot of time trying to reassure them that’s not a problem that’s typical for follicular lymphoma. Everybody wants to know their stage, of course. And I try to tell them, the stage doesn’t really matter that much in follicular lymphoma. In some cancers, the stage is a big deal. But those are cancers that you can kind of remove surgically.
But there’s really no role for surgery as a treatment in follicular lymphoma. The disease is typically very widespread in diagnosis, meaning it’s all over the body. And so when we do treat it, we pick treatments that will work everywhere. And our treatments tend to work just as well when the disease is at a more advanced stage. That’s why as the doctors, we don’t spend too much time worrying about the stage. It’s just not, it’s not as important in follicular lymphoma.
Lisa Hatfield:
Okay. Thank you. And just to clarify, when you mentioned that there is a mutation or often mutations in follicular lymphoma, is that in the cancer cells themselves, or is that in a mutation, like a BRCA mutation that a patient can be tested for? I presume it is.
Dr. Brad Kahl:
Right. That’s a great question. The mutation is specific to the cancer cells. So people are not born with this mutation. It’s not a mutation that you pass along in your family to children. It’s a mutation that is acquired in these cells at some point in the patient’s lifetime. Another confusing term is this whole idea of B-cell lymphoma or T-cell lymphoma.
And just to try to clarify that. So we have different kinds of lymphocytes in our body, and these lymphocytes, they have jobs to do as part of our immune system. And one kind of lymphocyte is a T cell, and that has specific roles in our immune system. And another kind is a B cell, and that has specific jobs to do in our immune system. Follicular lymphoma is derived from a B cell, a B-cell lymphocyte. So the…a B cell gets this mutation, and that turns it from a normal healthy B cell into a follicular lymphoma cell.
Lisa Hatfield:
Okay. Thank you for explaining that and for that overview. That’s really helpful. I appreciate that. So, Dr. Kahl, you also mentioned treatments and how oftentimes it’s not a cancer where you can just remove the cancer. Can you talk about some of the exciting developments with treatments and new innovative therapies, and what are the most important highlights for patients and families?
Dr. Brad Kahl:
Yeah. There’s a lot to talk about here. So I’ll start with how we approach a newly diagnosed patient, and then we’ll go into how we approach patients who have relapsed disease. So the most often, or the most common way a follicular lymphoma patient comes to medical attention is they just either notice a lump from an enlarging lymph node, or some enlarged lymph nodes are just found incidentally because they’re having some testing for some other condition.
And so, like I said, very often patients don’t have symptoms. That’s very typical. Occasionally, the patients will have symptoms, and those symptoms might be pain from a large lymph node mass that’s pushing on something. Occasionally, they might have fevers or night sweats. They wake up in the middle of the night just drenching wet, or unexplained weight loss. Those would be symptoms that can occur in follicular lymphoma. But most patients who come to see us for the first time don’t have symptoms.
When we have a newly diagnosed patient and it takes a biopsy to make the diagnosis, we then need to do the staging evaluation. So that involves some sort of imaging. And nowadays that’s usually in the form of what’s called a PET scan, which gives us a good snapshot of the whole body. And it’ll show us enlarged lymph nodes. And then the PET portion of the scan will show us if the lymph nodes are metabolically more active.
So they show up as these bright spots on the PET scan. And that’s what allows us to stage the patient. It tells us where the disease is located and how much of the disease we see. And so I’m often telling patients, I don’t worry so much about the stage. I worry more about the disease burden. So the way I explain that to patient is, suppose I could take all the follicular lymphoma cells out of your body, and I made a pile. How big is the pile? And that’s actually, I think, more important than the stage in determining our initial strategy.
Because believe it or not, if we have a patient who comes to us with a new diagnosis of follicular lymphoma and they have no symptoms, and it turns out that their tumor burden is very low, we often will recommend an initial approach of no treatment, which is a strange thing for patients to hear. And we spend a lot of time trying to explain the rationale for that. So I’ll try to explain that to you now. Follicular lymphoma is hard to cure.
So it’s this weird cancer in that it’s slow-moving. It often doesn’t make people sick, and we have good treatments for it, but curing it, like making it go away once and for all, proves to be kind of difficult. And studies in the past have shown if you have a patient who has no symptoms and is low tumor burden, that their prognosis is just as good if you leave them alone at the beginning. And many patients will not need any treatment at all for two years, three years, five years. I even have follicular lymphoma patients who I’ve been observing for more than 10 years that have never needed any treatment.
About two out of every 10 patients that are newly diagnosed can go 10 years without needing any treatment. So that’s why we’ll start that strategy for some patients. And that’s psychologically can be difficult for patients. You’re telling me I’ve got a new cancer diagnosis. You’re saying you have good treatments for it. And yet you’re saying you don’t want to use any of those treatments. And so it takes a lot of talking and explaining to try to get people comfortable with that.
Some people never get comfortable with that, I admit it. But some people get very comfortable with it. But it is a very appropriate initial strategy for a low tumor burden asymptomatic person just to observe and get a handle on the pace of the disease. If the disease starts to grow, or if the patient starts to get symptoms, we can start our treatment at that time. And the treatment is going to work just as well as it would have had if we started it last year, or two years ago.
So we feel like we’re putting the patient in no harm, no risk of harm by starting on this strategy of a watch and wait. On the other hand, some patients have high tumor burden, they have a lot of disease, or they have symptoms. And for those patients we need to start them on treatment because the treatment can put them in remission and get them feeling better. Right now, the most common frontline treatment in follicular lymphoma will be a combination of some chemotherapy and some immunotherapy.
The most commonly used regimen in the United States right now is a two drug regimen, a chemotherapy drug called bendamustine (Treanda), and an immunotherapy drug called rituximab (Rituxan). And you give that treatment every 28 days for six months. And it’ll put 90 percent of people into remission. And on average, those remissions last five plus years. And it’s a very, very tolerable treatment. It’s not too bad as far as chemotherapy goes. There’s no, most people don’t lose their hair. They don’t get peripheral neuropathy, that sometimes chemotherapy drugs give.
It’s not too bad for nausea and things like that. I’m not saying it’s easy or it’s fun. It’s none of that. But as far as chemo goes, it’s not too bad. And it’s effective, it is very effective. And I’ve given that treatment and I have people who are still in their first remission 10 years later, so you can get, for some people can get these really long remissions. But the reality is most patients, their disease does come back, they do relapse at some point. And then we have to start talking about what to do for second line treatment or third-line treatments.
And that’s where things have really taken off in follicular lymphoma in the last few years, there are a number of brand new treatment options in play for relapsed follicular lymphoma that are very exciting, and proves that we’re moving away from chemotherapy. We have drugs that are oral, that are, we call them targeted agents, they hit like a molecular pathway inside the cell a lot, and they kill the cells a lot differently than chemotherapy does. And we have a number of new drugs that work through the immune system, and try to attack the lymphoma that way.
So when we have patients who relapse, probably the most commonly used second-line treatment right now is a combination of a drug called lenalidomide (Revlimid), which is a pill that’s used in a few different cancers. It works very well for certain cancers, and it works well in follicular lymphoma. And that’s given with the immunotherapy drug called rituximab. And that was proven in a study to be very effective. About 80 percent of people will respond to the regimen, and that remission on average lasts in the two to three-year range.
So that’s probably the most commonly used second line regimen right now in the U.S. for follicular lymphoma. And then there are a number of treatments that are now available in third-line and beyond that are new within the past, say three, four years. And these newer treatments that I’m about to describe are now being tested as second line treatments and even as first-line treatments.
So it’s possible that some of these treatments I’m about to describe will become in the future, our go to regimens for first line treatment or second line treatment. And we hope they do move up, because that means they’re, it means they’re even better than what we’ve been using. So probably the treatments that we’re most excited about right now in follicular lymphoma are the drugs called bispecific monoclonal antibodies. There are two that are now FDA-approved. One’s called mosunetuzumab-axgb (Lunsumio), and that was approved about a year-and-a-half ago.
And the other one’s called epcoritamab-bysp (Epkinly), and that was approved just a month ago. And basically these drugs are infused or injected under the skin, infused intravenously injected under the skin and their proteins that will literally stick to the lymphoma cells. And when it does that, it kind of coats the cancer cells. And then after these bispecific antibodies coat the tumor cells, they literally will trick the patient’s T cells or healthy T cells to come in and attack the cancer.
So it’s a way of trying to trick the patient’s own immune system to come in and start fighting the cancer. And these two drugs are very promising in the relapse setting. They work about 80 percent of the time to get some kind of response. About 60 percent of the time patients will go into complete remission, which means we can’t find any evidence for the lymphoma on scans. And they’re both so new that I don’t think we have a full understanding of how durable these remissions are going to be right now.
It looks that like about, if you do get a complete remission, that about half of those patients are holding that complete remission at two and three years. But we’re, we don’t know about four years and five years yet because the drugs are too new. And we expect that if, as these drugs move up and are tested in the second-line setting and in the first-line setting, they’ll work even better because the cancer cells tend to be easier to kill in earlier lines of therapy. Other agents that have moved into the relapse follicular lymphoma space would include CAR T-cell therapy.
This is a fairly sophisticated complicated approach where you actually will run the patient’s blood through apheresis machine and you will extract the patient’s T cells and those T cells get genetically modified in a lab and then expanded and then are shipped back to the center and then re-infused back into the patient. So now again, we’re tricking the patient’s T cells into fighting their B-cell lymphoma.
And there are three CAR T products that are now FDA approved for use in follicular lymphoma, and they have very high response rates. With seemingly good durability we’re now getting three and four-year follow-up for these CAR T products with about half of people still in remission. The CAR T products probably have a little more toxicity and a little more risk than the bispecifics. So I think most of us are thinking we would try the bispecifics before CAR T, but there might be certain patients where a CAR T strategy is more appropriate to use before a bispecific.
So we’re very excited to have these tools in our toolbox. It’s always good to have more options. And then I should just mention the small molecule inhibitors. So here’s an example. Just this past year there was approval for a small molecule called zanubrutinib (Brukinsa). It targets an enzyme called BTK or Bruton’s tyrosine kinase. This is a pill really well tolerated. It’s given in a combination with an immunotherapy drug called obinutuzumab (Gazyva). This zanubrutinib-obinutuzumab combination got FDA-approved just this year for recurrent follicular lymphoma.
The results look very good for that. It’s very well-tolerated. There’s another oral agent called tazemetostat (Tazverik), which was approved a couple of years ago. It targets a mutated protein in follicular lymphoma. This is, again, is a pill super well-tolerated, very few side effects. So, there’s just a few examples for you of all the different treatment options we have for follicular lymphoma that has recurred after initial treatment.
And believe it or not, the decision-making can be difficult when you have so many choices and so many good choices, that’s a good problem to have. And I find myself a lot of times spending a lot of time with the patient and their family as we talk through these different options, and we try to think what’s best for them at this point in time, talking through the pros and the cons, how active it is, what side effects do we need to be concerned about. And it’s a lot for patients to digest when you have so many choices. But like I mentioned that’s actually a good problem to have.
Lisa Hatfield:
I think you’re right. There’s a lot of hope in those options. I do have two follow-up questions. One of them is when you talk about lenalidomide or brand name Revlimid, CAR T bispecific antibodies, this new small molecule, are these all quality of life is so important for cancer patients. Are these all limited duration treatments for recurrent disease when there’s a recurrence of the disease or are they long-term treatments for the disease?
Dr. Brad Kahl:
Yeah, really good question. And the answer is different for every agent. So I’ll try to just kind of run through the list. For the CAR T products, the three different CAR T products, it’s like a one-time treatment and then you’re done because the cells that get infused will persist in the patient’s body for months and months and months. So they’re infused and then the cells will hang around a long time acting on the cancer. So for the CAR T it’s a one-time treatment. For the bispecifics, the mosunetuzumab-axgb product is a time-limited treatment that is done in less than a year. The epcoritamab-bysp is designed to be given indefinitely.
So those are, there are some pros and cons of those two agents, the two small molecules that I mentioned, the zanubrutinib is meant to be given indefinitely and the tazemetostat is meant to be given indefinitely. And then the first one I mentioned was the lenalidomide. That is in follicular lymphoma that it was developed to be given for 12 months in this setting. So the duration of therapy is unique for each of the different agents that I mentioned.
Lisa Hatfield:
Okay. Thank you for that overview of all those emerging therapies. That’s great to know for patients, Dr. Kahl. All right. It’s that time where we answer questions we’ve received from you. Remember, as patients, we should always feel empowered to ask our healthcare providers any and all questions we might have about our treatment, our disease, and our prognosis. Please remember, however, this program is not a substitute for medical care. Always consult with your own medical team.
So, Dr. Kahl, we have several patients who have submitted some questions. The first question is regarding emerging technologies. And I think that you probably have answered that very well actually in a discussion here. So the second question this patient had is how might future innovations build on the latest treatments to offer even better outcomes for patients? You, I think maybe have touched on that, but maybe speak to that a little bit more as far as longer remissions. Yeah.
Dr. Brad Kahl:
Right, right. So I think right now the main emphasis in research is to take some of these really promising drugs that were developed for relapsed follicular lymphoma and do two things with them, test them in combinations in the relapse setting to see if you can make them even more active. So an example of that would be take the drug lenalidomide, which is really active in the relapse setting and pair it with the drug mosunetuzumab-axgb, which is very active in the relapse setting, and pair them together and see if you can get better results than either drug alone.
So there are studies trying to answer questions like that at this time. And then the other area of major interest is to take these promising new treatments approved in the relapse setting and test them upfront. So there are studies being literally designed right now as we speak that will test bispecific monoclonal antibodies in the frontline setting.
So patients can envision being offered a chance to have a chemo-free strategy where they’re just getting a bispecific monoclonal antibody as their initial treatment. And there are studies that will test these drugs as single agents, and there are studies that will test these drugs in combinations with other agents in the frontline setting, like lenalidomide, for example. So we have no results from any of these trials yet, but these trials are just starting to enroll patients and this could fundamentally change the way we’re managing follicular lymphoma in the future if any of these new strategies turn out to be more promising than what we have done historically.
Lisa Hatfield:
Thank you. Okay. Another question, Dr. Kahl. How do outcomes differ for patients with relapsed/refractory disease compared to those who respond well to initial treatment?
Dr. Brad Kahl:
So that’s a really good question. And when we have a patient going through frontline treatment, we’re all really crossing our fingers that that first remission is incredibly durable. Because when the disease relapses, the remissions do tend to get shorter and shorter and shorter, which is frustrating for everybody.And so we love it when we get a nice long first remission. And in the older days when all we had to offer was chemotherapy and some different immunochemotherapy regimens, the remissions in second line and third line might be two years or one year. It can get frustrating as you go through treatment after treatment after treatment. It’s hard on patients. The side effects start to accumulate. And that’s one of the reasons we’re so excited about all these new agents that we have for relapsed disease with the bispecifics and the CAR T products and the small molecule inhibitors like tazemetostat and zanubrutinib. Because it appears as though these remissions for relapsed disease might be getting longer than what we have seen historically. So there’s no question that dealing with relapsed follicular lymphoma is more difficult than dealing with frontline follicular lymphoma. But we’re optimistic that these newer treatments we have are improving outcomes for patients with relapsed disease.
Lisa Hatfield:
Okay. Thank you. And another question, which patients are considered the most vulnerable when it comes to follicular lymphoma and why, and what measures can be taken to better support these populations in terms of treatment and care? And I’m not sure if they’re talking about different age groups or ethnic groups or geographic groups like rural versus more urban areas, but if you can speak maybe to general terms to answer that question, that would be great.
Dr. Brad Kahl:
Yeah, right. Well, the first thing that comes to mind are older patients. Older patients are always more challenging to take through cancer therapies. The older patients are more fragile. They don’t tolerate the treatments quite as well. They don’t have the physiologic reserve. They’re more susceptible to complications and infections. So I always think when we have older patients that need treatment in follicular lymphoma, the doctor has to be extra, extra careful, sort of the Goldilocks principle. You don’t want the treatment too hot and you don’t want it too cold, too hot, it might work great, but you might get unacceptable side effects too cold, maybe no side effects, but not enough activity against the disease. So we’re always trying to get that patient the best remission we can get them, but doing the least amount of harm along the way.
So I think that takes a little bit of art, a little bit of experience to figure out how to get your older more fragile patients through follicular lymphoma therapy. And then I think the whole idea of patients who live in rural areas, that can often be challenging too, because they may be hours and hours away from medical care. So if they do have a complication of treatment, an infection, for example, it can be challenging to get them the care they need in a quick amount of time. So when I have patients who I know live way out in the country, far away from our center, I just, we always give them a card, it’s got our phone number and I’m like, you feel like something’s going wrong, call us. I don’t care if it’s 2 in the morning, you call us.
It’s not your job to figure out what’s going wrong. That’s our job. It’s just your job to describe to us what you’re experiencing and then we’ll figure out over the phone whether we want you to drive the three hours to come see us or whether we think you just need to go to the closest place, which might be 30 minutes away. So at least you’re in the hands of some medical professionals. And then they can call us with an update on what they’re noticing, what the tests are saying. So taking care of patients who live far away from the medical center poses some additional challenges.
Lisa Hatfield:
Okay. Thank you. And that’s a great takeaway for patients. If you have a question, call your provider. They can help take the stress away from making that decision yourself.
Well, here’s a loaded question for you, Dr. Kahl. Why does relapse happen in the first place, and what are the changes in the body that signal when and if treatment is likely going to fail?
Dr. Brad Kahl:
Boy, we wish we understood why relapse happens in the first place. Last I mentioned, most of these treatments can get people into remission, which means that they can kill the vast majority of the cancer cells, maybe 99.9 percent of them, but for some patients, there’s just a few stubborn cells that remain behind. Maybe those cells are just sitting there, not growing at all, which follicular lymphoma cells can do.
And when the cells are not trying to divide, not trying to grow, they’re kind of protected from killing. They’re just sitting there doing nothing. And so we think it’s this property that how the cells kind of protect themselves. And so these rare cells that are just kind of sitting there, quiescently not growing, not dividing, these might be the cells then that just hang around for years and then contribute to that relapse five years down the road.
But I admit we don’t fully understand why one patient will relapse two years after a treatment and the next patient is still in remission 10 years later. These are things that we don’t fully understand. Every patient’s lymphoma is a little different, I’m afraid. So two people with follicular lymphoma, they don’t really have the same cancer, cancer, they are sort of like snowflakes. No two are alike. And so they can have different mutations inside the cells that’ll make the cancer behave a little differently from one patient to another. It might make it respond to treatment a little differently from one patient to another. And so what is true for one follicular lymphoma patient may not be true for another.
So if a patient’s symptoms are not being relieved, that might be a clue that the treatment isn’t working as well as we want it to. And then in some cases the only way to figure out if a treatment is working is by scanning. So we’ll have a before picture from a PET scan or a CT scan, and then we’ll take them through a few cycles of treatment, and then we’ll get another scan to prove that the treatment is working like we want it to work. And if it’s not working like we want it to work, then we’ll say, okay, this one isn’t working for you. Let’s go to the what we think is the next best option for you.
Lisa Hatfield:
Okay. Thank you. And just listening to you and hearing about all these nuances with follicular lymphoma, I would probably recommend as a patient myself with a different kind of cancer, seeking out at least a consult from somebody who specializes mostly in follicular lymphoma, at least a hematologist who can tease through some of these nuances to help you as a patient find the best treatments and therapies and quality of life. So just a little tidbit there. So, Dr. Kahl, thank you so much for being part of this Patient Empowerment Network START HERE program.It’s these conversations that help patients truly empower themselves along their treatment journey. And on behalf of patients like myself and those watching, thank you for joining us, Dr. Kahl.
Dr. Brad Kahl:
Thank you for having me.
Lisa Hatfield:
I’m Lisa Hatfield, thank you for joining this Patient Empowerment Network program.
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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.
Related Resources:
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Expert Overview | AML Treatment Options and Phases of Therapy |
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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.
Elevate | What You Should Know About Your Role in AML Treatment and Care Decisions
Elevate | What You Should Know About Your Role in AML Treatment and Care Decisions from Patient Empowerment Network on Vimeo.
How can you elevate your AML care and treatment? AML expert Dr. Gail Roboz discusses the importance of participating in AML treatment decisions, reviews key factors that may impact therapy options, and shares advice for advocating for yourself.
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:
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Thriving With AML | Advice for Setting Goals and Making Treatment Decisions |
Expert Advice | Managing AML Symptoms and Treatment Side Effects |
Transcript:
Katherine Banwell:
Hello, and welcome. I’m your host, Katherine Banwell. It’s no secret that the quality-of-care patients receive can vary, and patients who are educated about their condition and involved in their care may have improved outcomes. That’s why the Patient Empowerment Network created the Elevate series, to help AML patients and their care partners feel well-informed when making treatment decisions with their healthcare team.
In today’s program, an AML expert will join us to share advice for accessing better overall care. Before we get into the discussion, please remember that this 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. Gail Roboz. Dr. Roboz, would you please introduce yourself?
Dr. Gail Roboz:
Absolutely. Thank you so much for having me. My name is Gail Roboz. I’m a professor of medicine and director of the clinical and translational leukemia programs at Weill Cornell Medicine and the NewYork-Presbyterian Hospital in New York City. Thank you again for having me.
Katherine Banwell:
Well, thank you so much for joining us today. We really appreciate it. I’d like to start by discussing your role as a researcher. You’re on the frontlines for advancements in the AML field. What led you here, and why is it important to you?
Dr. Gail Roboz:
So, I’m actually asked that question quite frequently, because AML is a challenging, difficult, scary disease, and people don’t necessarily assume that somebody in medical school would gravitate toward it.
But I have to say that what is incredibly fascinating back then and now about leukemia is the continuous access to the disease. Patients will maybe giggle or groan as I’m saying that, because you can get a blood sample really anytime. You can even get a bone marrow sample anytime, although patients don’t enjoy that so much.
But from a research perspective, it is absolutely extraordinary to be dealing with a disease where you can, in real time, truly run back and forth to a laboratory and see what’s happening, what is the new drug or the old drug doing, what’s happening with the patient, and I would say that from a fascination of a medical student perspective that grabbed me then and still does today.
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:
Right. 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?”
Katherine Banwell:
Okay. I’d like to turn to test results for a moment. What sort of tests should be done following an AML diagnosis?
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.
Katherine Banwell:
I’d like to add that if you, the viewer, are interested in learning more about AML testing and treatment, PEN has a number of resources available for you. You can find these at powerfulpatients.org/AML, or by scanning the QR code on your screen.
Before we get into specific treatment types, Dr. Roboz, would you provide a brief explanation of the phases of therapy for AML? You mentioned induction therapy earlier. Would you tell us what that is?
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.
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 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.
Katherine Banwell:
The symptoms of AML as well as the side effects of certain medications can vary greatly among patients. So, how do you approach symptom management with your patients?
Dr. Gail Roboz:
Patients will giggle because I repeat this line. You have to be afraid of the disease, not the treatment. I think that if you read the package insert on a Tylenol, you’re certainly not going to think you’re going to live for more than 20 minutes if you take one of those. You can certainly appreciate that, with chemotherapy drugs and including some of the novel agents that I’m talking about, if you read package inserts and look at some of the signs and symptoms and things that can happen, it’s extraordinarily overwhelming.
I think that a lot of what I do for patients is I keep them close. Because if the patient is in the hospital or coming in very frequently in clinic, I think that that everyday assessment of, “What are you experiencing?” and “What can I tell you is the disease’s fault, and what can I tell you is the medication’s fault?” is so, so important.
Especially in the newly diagnosed patients, where the disease is active. Of course, we want to try to minimize anything that we can do to make the process better for patients, more comfortable for patients, but there are certain things that we do tell people, “You’ve got to slug through this particular problem, because this is the disease’s fault.” This is different from a patient in remission, where they might be getting ongoing therapy with something, or we say, “Hey, wait a minute. You’d be feeling fine, except now you’re taking this medication. How do we minimize messing up quality of life in remission?”
Because we want you to feel great when you’re in remission. I think the real answer of that is to have a really close collaboration with the healthcare team, and for the patients to really understand – I repeat this because it’s so important. What is the disease’s fault, and what is the treatment’s fault? If there’s something that is therapy-related, do I have a substitute or do I not have a substitute?
Because if the drug is essential to get us where we need to go, well, what can we do to manage comfort and to manage symptoms until you get to the place where your marrow is working again?
Katherine Banwell:
That’s great advice, Dr. Roboz. I would like to get to an audience question that we received prior to the program. This one comes from Johanna. “How can I better understand my lab test results? What questions should I be asking my provider about those results?”
Dr. Gail Roboz:
One of the things that I would say to patients is to be careful when interpreting your own results, because I really am not exaggerating to say that patients have had absolute trauma looking at things that I look at it and say, “Oh, this looks great.” So, the first thing is, be careful being your own doctor.
The second thing though is that the author of the question has to understand that there’s going to be a tsunami of data coming in with respect to AML treatment. Sometimes in the hospital on a daily basis when you’re in the middle of an induction, there is a true – tsunami is the right word – a deluge of data, and you have to work with your team to say, “What am I following here? What’s important at this phase in my treatment? What’s the number I’m looking at?” Patients sometimes tell me, “I don’t want to know any of this,” and I’m fine with that.
I think it’s actually okay. Sometimes patients will say, “Give me guidance,” and I will be specific. Because you can actually have a leukemia induction patient where every single laboratory value is abnormal. They might be getting pushed to a device, in the morning, sitting in the hospital on your iPad, 50 abnormal results. You’re trying to battle back the disease and be positive and advocate for yourself, but there are 50 abnormal results in front of you.
I think you have to really work with the team to say, “What am I looking at today? What are the numbers that are the really important ones? There are 50 abnormal ones here; everything is getting a yellow or a red light in this. How do I go through this?”
And to appreciate, also, that at different points in the treatment, the beginning of treatment induction post-remission therapy, you’re looking for different things. So, work with your team so that you’re not assessing every single result with equivalent weight, because I think you’re going to stress yourself out.
Katherine Banwell:
That’s great advice, Dr. Roboz. Thank you. As we close out the program, I’d like to find out what you would like to leave the audience with. Why are you hopeful?
Dr. Gail Roboz:
AML is changing incredibly rapidly. And I can tell you it is a lot more fun to be an AML doctor now than it used to be, with respect to what I am offering for patients. We have always fought really, really hard to have our wins, but we’re winning more. I do think that it is a complicated space to navigate for patients, but there is room for a lot of optimism.
I think we are getting patients transplanted – patients that we never thought would ever go through a transplant or getting transplanted. Patients who never had a chance of even living more than six or eight months or living much longer than that. Is it perfect? No. Do we have as many cures as we want?
No, but there’s a lot going on. I think if patients feel that excitement, they will also feel the need to ask about those clinical trials. Because I think that for a lot of patients, clinical trials is an area where they would be worried. They’re not sure that they want to. “I don’t want to be a guinea pig,” and yet here I can say in the AML space, one after another after another drug approvals in the last several years, with the patients on those trials being awfully happy that they participated.
So, I think that it’s a very, very terrifying diagnosis. There’s nothing that I can do to take the sting out of that. But try to find yourself in an optimistic place with options that are being offered to the very, very, very best that we can do. There are patients who are listening, I’m sure, who have relapsed or refractory disease who are not feeling that optimism.
I want to address you specifically, because we don’t have enough yet. We’re trying. When you have AML that has come back or come back multiply, that’s dangerous and difficult. But for those patients in particular, try really hard to get onto clinical trials. If the drugs that we have out there – if you’ve already taken them and they haven’t worked for you or if they’re not serving you well, if you’re in good shape and the drugs that we have aren’t good enough, well, let’s see if we can get you on something that’s investigational.
Katherine Banwell:
Dr. Roboz, thank you so much for taking the time to join us today.
Dr. Gail Roboz:
Thank you for having me.
Katherine Banwell:
I also want to thank 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 joining us today.
Advanced Prostate Cancer: What You Need to Know About Evolving Treatment and Research
Advanced Prostate Cancer: What You Need to Know About Evolving Treatment and Research from Patient Empowerment Network on Vimeo.
Research is evolving quickly, leading to an increase in treatment options for advanced prostate cancer patients. Expert and researcher Dr. Rana McKay reviews current prostate cancer treatment options, discusses where clinical trials fit into a care plan, and shares advice for partnering with your healthcare team.
Dr. Rana McKay is a Medical Oncologist at UC San Diego Health. Learn more about Dr. McKay.
See More from Evolve Prostate Cancer
Related Resources:
Which Factors Impact Advanced Prostate Cancer Treatment Decisions? |
How to Play an Active Role in Your Prostate Cancer Treatment and Care Decisions |
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Transcript:
Katherine:
Hello and welcome. I’m your host, Katherine Banwell. When advanced prostate cancer patients discussed potential treatment approaches with their healthcare team, it’s important that they understand all of their options including where clinical trials fit in. So, the patient empowerment network created the Evolve Series, to help patients understand the latest research and how it may impact them. In today’s program, we’re joined by a prostate cancer expert who is going to explain and discuss research highlights, and provide tips for having productive conversations about your care. Before we meet our guests, though, let’s review a few important details.
The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access a guide to help you follow along during the webinar. At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars. And finally, before we get into the discussion, please remember that this 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. Rana McKay. Dr. McKay, welcome. Would you please introduce yourself?
Dr. McKay:
Absolutely. My name is Rana McKay, I’m a genitourinary medical oncologist, at the University of California in San Diego. It’s a pleasure to be here, with you, on this program today.
Katherine:
And the sun is shining.
Dr. McKay:
Yes.
Katherine:
Which, is always good. Well, thank you so much for taking the time to join us today. Before we get into the discussion, Dr. McKay, I’d like to have you tell us how the landscape of advanced prostate cancer has changed over your career.
Dr. McKay:
Oh, my goodness. It has absolutely rapidly evolved over the last decade. I think when I was just starting my career, it was right around the time where Abiraterone and Enzalutamide were being heavily tested and just getting approved and entering into the clinic. And as we think about all of the evolution that’s happened since that time, we now have multiple androgen receptor pathway inhibitors in the clinic. We have radioligand therapies in the clinic, radium-223. The first radioligand therapy across any solid tumor malignancy to improve overall survival and on the heels of that, most recently, lutetium PSMA, which is a targeted radioligand therapy.
There’s several different kinds of chemotherapies, and I think two more diagnostics have evolved. We are now integrating molecular profiling across multiple areas in the disease natural history and actually have several FDA-approved treatments based off of results of molecular profiling, whether that be germline hereditary testing or just tumor testing like, PARP inhibitors and immunotherapy. And then, additionally, to kind of continue on that same thought of our diagnostics changing is one of the greatest disruptors in our treatment of prostate cancer has been the introduction of PSMA PET imaging that has really revolutionized our ability to be able to detect disease at lower levels of PSA.
And that’s opened up options for focal therapy, radiation therapy, and other sorts of strategies. So, it’s really been just remarkable, all of the different advances that have occurred in prostate cancer over the last decade.
Katherine:
Well, let’s dive into developing research and what it could mean for patients. Are there recent research highlights that you could share with the audience?
Dr. McKay:
Absolutely. I think the newest approvals that have occurred in prostate cancer have been the approvals of combination PARP inhibitors, which block the ability of cancer cells to repair their DNA combined with hormonal agents such as abiraterone (Zytiga) or enzalutamide (Xtandi) for patients who have specific mutations in their tumor and their tumor is no longer responding to treatment. Those are the newest FDA approvals that were recently highlighted and shared.
Katherine:
What areas of research do you specialize in?
Dr. McKay:
The areas of research that I specialize in are particularly around novel therapeutics for patients with advanced prostate cancer, biomarker development precision medicine strategies for patients across the spectrum. And actually, also, in the localized setting, thinking about how we can attempt to cure more patients with prostate cancer by integrating our systemic therapy with surgical and radiation strategies to improve survival outcomes for patients and ultimately, cure it for patients by using effective systemic therapy early on so patients never recur.
Katherine:
Yeah. We’ve been hearing a lot recently about innovations in technology. How are these advances accelerating prostate cancer care?
Dr. McKay:
Innovations of technology have absolutely been revolutionizing prostate cancer care I think from the diagnostic side, there’s new imaging modalities that are getting more refined. On the molecular side, there’s now different kinds of genetic tests. And our ability for us to do these tests, and do them quickly, and get results in real time that we can make decisions on we’ve come a long way from when we first sequenced the human genome. We’re now able to do that so quickly multiple times over in a very streamlined kind of way. And then, I have to say that there’s been tremendous improvement in our modalities of administrating therapies.
So, our therapies are getting more novel, they’re getting more precise. What I mean, by that is targeted radioligand therapy, targeting linking a small molecule that binds PSMA, labeling it with a payload that is radiation therapy or kind of radio therapy/radio particle doing the same thing with chemotherapy, developing antibody drug conjugates. There’s androgen receptor degraders. There’s different ways of administrating immunotherapy by specific antibodies. So, there’s just the different sorts of treatments that are out there.
We’ve just come such a long way from hormone therapy, which is still very important in chemotherapy to other different modes of action with the different systemic treatments we have.
Katherine:
What about individual patients? Is there research into understanding a person’s – just one person’s disease?
Dr. McKay:
Absolutely. I mean, that is in essence, precision medicine. I think we are now molecularly profiling tumors that is standard of care for anybody with advanced disease to undergo hereditary tumor profiling and – or hereditary profiling of just normal cells in the body, if there’s any sort of genetic abnormalities. But also, the tumor itself, and able to do that all for the actual biopsy specimen, or surgical specimen, and also blood. And then, based off of that individual’s genetic makeup, or the genetic makeup of the tumor, or the immune profile of the tumor actually trying to target therapy.
There is a clinical trial that we are eagerly developing through the alliance, which we hope will open to enrollment before the end of the year, called the PREDICT Study. And this study is using that very notion of taking somebody’s DNA and RNA from their specific tumor, and based off of their results, strategizing the treatment around what kind of genetic makeup is in the tumor. And I think we’re moving towards that.
Katherine:
What about common genetic mutations and what are you learning about people who have other genetic mutations like the BRCA mutation?
Dr. McKay:
For patients who have BRCA mutations, first I’ll say, the prevalence of BRCA mutations varies across the stage of prostate cancer that somebody has. In the localized setting, the prevalence is a lot lower on the order of 2 to 4 percent depending on somebody’s risk profile. In the advanced setting, it is higher, 6 to 8 percent. Patients who have BRCA alterations are particularly susceptible to PARP inhibitors, which are oral drugs that can be given that when given in an individual who’s got a BRCA mutation, can cause cell death; can cause a tumor cell to die. And so, that’s a very good thing.
I think the other thing, if thinking about the type of BRCA alterations, if there’s something that’s hereditary, this information is prognostic and predictive in that in can guide how people are going to – how we think they may do and what they may respond to. But it’s also really important because it can inform cascade testing for family members. It could also inform screening for secondary cancers in that individual who has prostate cancer with a known BRCA alteration. So, I think there’s a lot of personalization that happens based off of the molecular profiling results.
Katherine:
It’s all so exciting, Dr. McKay. But progress can only be made with patient participation in clinical trials, as we know. So, when should a patient consider participating in a trial?
Dr. McKay:
Thank you so much for bringing this point up. I think our clinical research is critically important to advancing the field. Clinical trials, I think, are really – they offer our patients the treatments of tomorrow today, quite honestly. And I think the way trials are designed, they’re designed to test different treatment modalities, test in reference to the standard of care. I think at any point in time, anybody can think about enrolling on a clinical trial. I think sometimes there’s this false notion that, “I’m not going to enroll in a trial until later on, until I’ve failed all different kinds of treatments.” That’s not true.
I think at any juncture along the way where a decision is being made around initiating a systemic therapy, or proceeding with a surgical intervention, or radiation intervention it’s always worthwhile to stop and ask, “Are there any clinical trials that I could be eligible for right now? And if so, what are they? So, I think it’s really important, I think, for patients to know that and to ask of their clinicians that are caring for them, “Are there any clinical trials?”
And it may be that patients, not to say, may need to travel, but if they’re not necessarily at that institution where somebody may be receiving their care with a clinician asking their doctor, “Are there other trials at places close by where I can go and explore?” I think that’s a really important thing.
Katherine:
Yeah. That’s good information. What about common misconceptions? What are you hearing from patients about their fears and hesitations about participating in the trial.
Dr. McKay:
Yeah. I think a lot of patients have a fear of, “I don’t want to be a hamster or a guinea pig. I don’t want to get placebo. I don’t want to get suboptimal care.” So, I think, to step back, I think the clinical trials are designed where actually patients are followed very, very closely, probably even more closely than I think would be in general with laboratory tests, PSA testing, imaging, at critical time points to assess that any therapies or strategies is working. Many trials are not necessarily placebo-controlled trials.
Placebo-controlled trials are really only utilized in the context when somebody may – where the standard of care is to either do nothing or do one drug alone, not two drugs, and then, somebody’s getting one drug and getting a placebo. So, the placebo-controlled trials are really, first off, they’re later-staged studies, they’re usually Phase III studies, or large Phase II studies that have gotten pretty far on the runway of clinical trial and clinical drug development.
And it’s in the context of, you know, “Well, if I didn’t do the clinical trials, I’m probably not going to do anything,” or I’m not going to – you know, “If I decided to not do the trial, I would get no treatment, but if I’m doing the trial, there’s a 50 percent chance I’ll get no treatment and 50 percent chance I may get something. So, we have to think about, “Well, what is the standard of care?” and the standard of care matters because that is what it’s being compared to. If the clinical situation is that the standard of care is to monitor, then that’s where a placebo may be utilized.
But if a standard of care is that somebody should get treatment with X drug, then that X drug would be in the controlled arm of the study.
Katherine:
Yeah.
Dr. McKay:
But not every trial has a placebo.
Katherine:
What would you say to someone who is nervous or hesitant about participating in a trial?
Dr. McKay:
Yeah. Very good question, I think. Talk to your clinician. Talk to your doctors about those fears. What are the reservations? What are the concerns? Sometimes, I think the unknown is always – the fear of the unknown kind of causes a lot of angst. But when people are on a clinical trial, when you’re on a clinical trial, you are in control. Some people don’t believe that, but you are, at any point in time, you can decide to stop. You don’t even need to have a reason for why you decide to stop. At any point in time, if something is not working for you, you have choice.
And so, I think that is something that is really important for patients to know that you’re actually in control, you’re being watched very closely, being watched very carefully for safety toxicity. If there’s a toxicity, people are not going to – you’re not going to just stay getting the same regiment in the exact same way if you’re not tolerating it. If something isn’t working, you’re not going to continue receiving the therapy that’s no longer working just because you’re on a clinical trial.
Katherine:
Right.
Dr. McKay:
And you’re in control; at any point in time, you could say, “I don’t want to participate anymore.”
Katherine:
Yeah. Are there barriers for accessing trials? And if so, do you have any recommendations for how to tackle those?
Dr. McKay:
Yeah. I think there are barriers to accessing trials. I think it can be very overwhelming because there’s thousands of clinical trials that are being conducted for people with prostate cancer. And I think as a patient, sometimes it’s hard to navigate that. But I think the thing to take home is that you do not have to do it alone, and you should not do it alone because I think half of the trials that are out there, the large bulk of them may not necessarily be directly applicable to you or relevant for you.
And so, I think talking to your clinician about that, I think seeking care, even if just for a second opinion at an NCI-designated cancer center, or NCI-designated comprehensive cancer center is probably a good idea. You know, if you’re hearing the same message from your local clinician then that’s great. If there’s more options that are being presented to you, that’s great, those are more options that you could tap into. I think talking to patients who have gone on a trial may also help away some of the fear around participating in a clinical trial, and there’s lots of platforms where that could take place either asking your physician, or the American Cancer Society, or other societies can help connect patients to one another.
Katherine:
Okay. I’m glad you mentioned some of the resources because that’s what I was going to ask you about. Well, I want to mention to our audience that if you want more basic information about prostate cancer, PEN has created a prostate cancer toolkit, which includes information about diagnosis and staging. And you can find it at powerfulpatients.org. So, before we move onto understanding current treatment options, Dr. McKay, what are the goals of advanced prostate cancer treatment? And how do they vary by patient?
Dr. McKay:
Yeah. I do think the goals can vary. I think in my mind, a lot of times, it’s making people live longer, making them feel better. Those are the two salient goals and if our therapies are not achieving one or other of those two goals then we need to rethink the strategy. But different people are different, and they may weigh the risks and benefits of any given therapy, or the slated benefit with the slated risk through a different lens. And I think it’s critically important to ensure that you’re having those communications with your doctor about the things that matter to you and the things that are really important to you.
Especially, for people who have advanced prostate cancer. So, I think that can help your clinician strategize, “Okay, is this an individual who wants the kitchen sink everything that I can do even if that means more toxicity that I’m going to offer this thing? Or is this a situation where, you know what, unless there’s data that the kitchen sink is going to work, I really kind of want to temper things and try an approach that’s going to be effective, but maybe not associated with that degree of toxicity.” So, those kinds of conversations absolutely need to be happening.
Katherine:
Yeah. With all the recent advances in treatment, is there a standard approach now to treating someone with advanced disease? And if so, what is it?
Dr. McKay:
Yeah. There absolutely is a standard approach. There’s guidelines that are based off of the FDA-approved regimens of the different agents that can be utilized. There’s data regarding sequencing though, I think there’s more data that needs to be had on sequencing. There are guidelines on when to do germline testing, when to do tumor profiling, when to integrate PSMA PET imaging, the standard hormonal agents, who to use them. So, I do think that there are – there’s a set framework of appropriate management and treatment. But there’s a lot of personalization that is overlaid on top of that rubric. And I think that’s the art of medicine.
Katherine:
Right. Is there testing to understand if a patient’s disease is more aggressive? Or maybe will respond to a certain type of therapy before you begin it?
Dr. McKay:
Yeah. A very good question. And I think predictive biomarkers, as you described them, there are several for men with prostate cancer, but there’s not a ton of them. So, we know that homologous recombination repair alterations, HRR, gene alterations, particularly BRCA 1, 2, probably 2, we know that those are biomarkers of response to PARP inhibitors. We know that patients who have high tumor mutation burden, or have a mismatch repair, that those are markers of response to immunotherapy. We know that if people have a certain level of PSMA PET vividity on their PET scan, that that’s a biomarker for receiving lutetium PSMA.
Those are the main biomarkers that are actually in use in the clinic to date. But I think there’s a lot more that I think are being explored from mutations in the androgen receptor, or amplifications in the androgen receptor, being potentially predictors of response to different degraders, different kind of hormonal agents. There’s certain tumor suppressor gene mutations that may predict that patients may do a little bit better with chemotherapy. So, there’s other markers that are being looked at, but they don’t have the same robustness as the BRCA 1, 2 and other ones that I talked about.
Katherine:
Yeah. How does a patient’s health and lifestyle impact what treatment approach is right for them?
Dr. McKay:
I mean, health and lifestyle, diet, and exercise, nutrition, sleep are so important. I think that one of the backbones of treatment for hormonal therapy is androgen deprivation therapy. There can be negative consequences with regards to muscle mass, bone mass, other things related to that therapy. So, I think it’s critically important for patients to maintain a healthy diet, making sure they’re getting appropriate exercise, weight-bearing, resistance training.
And I think, too, this helps people with their functionality, with their ability, their reserve, and ability to tolerate treatment or tolerate more aggressive treatment. So, half of my clinic is talking about diet and exercise, and how to optimize individual health when people are on therapy.
Katherine:
Yeah. Mentally, a good diet and sleep –
Dr. McKay:
Yes.
Katherine:
And exercise is going to be helpful.
Dr. McKay:
Yes.
Katherine:
As well. What about comorbidities? Do they play a role?
Dr. McKay:
They absolutely do play a role. I think comorbidities like cardiovascular disease, diabetes absolutely can play a role. The hormone therapies, patients can have a propensity to gain weight, they can have a propensity to have worsened cholesterol being on hormone therapy, which can then affect somebody’s cardiovascular health. And so, some of the drugs cause increased hypertension. So, I think understanding the different comorbidities that any individual may have is important in selecting the best therapy, “Well, actually, if you’ve got X, Y, Z going on, maybe I’m going to shy away from this, but lean more towards that.”
I think making sure that your physician knows about that and knows about changes that happen along the way. Sometimes, people with prostate cancer, many a times they have a long, natural history where they’re seeing the physician caring for them for their prostate cancer over many, many years. And somebody’s medical history, when they first saw that individual, it’s going to change and evolve over time as different things happen. And so, I think keeping your clinician that’s caring for you for your prostate cancer informed of all the other non-cancer things that are happening I think is a really good idea.
If you had a fracture, that’s actually a really important thing for somebody who’s got prostate cancer. Or “Gosh, my primary care just started me on Metformin because they think my blood sugar is a little bit off.” These are important things, I think, for clinicians to know about.
Katherine:
Yeah. It’s all about communication, isn’t it?
Dr. McKay:
Absolutely. Yeah.
Katherine:
Don’t worry about over-sharing.
Dr. McKay:
Yeah.
Katherine:
Yeah. Speaking of sharing, shared decision-making has become the gold standard, really, for encouraging a successful relationship between a patient and their healthcare team. What does shared decision mean to you as a provider?
Dr. McKay:
Yeah. I think shared decision is an open dialogue. I think it’s an open dialogue with the physician, with the patient, sometimes, often times, the patient’s caregivers, and families, and loved ones may be involved in that process, where we’re talking about, first off, establishing the goals. Well, what are the goals? And I think, when we start with the goals then, we can say, “Okay. Well, what are the things that we can do to achieve those goals?” And I think sometimes we just dive right into, “Well, what are we going to do with the next step?”
So, I think establishing what the goals of therapy are the things that matter to any individual patient and their family is important. And then, from there, working on, “Okay. Well, aligning with those goals, these are the different things that you can do. These are the pros and cons of the different things that you could do,” and making an informed decision about the next step.
Katherine:
What questions should a patient ask about potential treatment options?
Dr. McKay:
One, what are the different treatment options? You know, sometimes I think that statement doesn’t get said enough. What are the standard of care options? What are the clinical trial options? Ask are there radiation therapies, surgical options? That may be a relevant question for some individuals, some individuals, not. Being very open like, “Okay, I’m hesitant about chemo. Let me explore that.” Well, where does that hesitancy stem from? What’s the fear about chemo? Are there chemotherapy-sparing options right now? Or how can we kind of dispel the fear or myth around chemotherapy?
So, I think these are the questions that I think a patient can ask. How is a therapy administered? Where do I go? How would I receive different therapies are given at different modes of administration? I think those are good questions. Who do I call if something happens to me on the weekend or on a holiday? Who do I reach out to? What are the phone numbers? Give me all the phone numbers. Get them in my phone. Save them in there, so you know, who to reach out to if you ever need something, if you ever need assistance.
Katherine:
Yeah, that’s really good advice. Why should a patient consider finding a prostate cancer specialist?
Dr. McKay:
I think a patient should consider finding a prostate cancer specialist because quite honestly, the field of oncology is getting to be so expansive, and there’s so many changes in guidelines on a monthly basis, sometimes across all the different malignancies. So, I think having a specialist who understands the nuances of the different iterations of treatment for people with prostate cancer, and how to personalize that for a given patient is really important. And I think it can be associated with improved outcome.
I will say that the note about clinical trials, there have been several studies that had been conducted that have actually noted that patients who enroll on a clinical trial, whether or not that clinical trial is positive or not, independent of the results of the trial. But just enrolling on a clinical trial is associated with improved outcome. And I think a lot of it stems with where people get their care, eligibility for trials, the scrutiny that happens when people are on trials, and sort of, level of expertise where people get their care and so forth.
Katherine:
Yeah. Thank you for sharing all of this information, Dr. McKay, it’s really vital. As we close, what final thoughts would you like to leave our audience with? Why are you hopeful?
Dr. McKay:
I am very hopeful because of all of the amazing technologies that are in the pipe right now, currently in development, some early on, some close to the finish line that I think are certainly going to change the way that we view and treat prostate cancer. I think it’s exciting to see where the field has come and where the field is going, and know that you are not in this alone, and there’s a lot of progress that is being made, and a lot of hope that is out there for individuals who have prostate cancer.
Katherine:
Well, Dr. McKay, thank you so much for taking the time to join us today. We really appreciate it.
Dr. McKay:
Wonderful. It’s my pleasure.
Katherine:
And thank you to all of our collaborators.
If you’d like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following the webinar. It will help us as we plan future programs. To learn more about prostate cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us.
PODCAST: What Non-Small Cell Lung Cancer Treatment is Right for You?
What’s the best approach for YOUR lung cancer? Dr. Isabel Preeshagul discusses the importance of engaging in your lung cancer care decisions, shares advice for working with your team to determine a treatment approach, and reviews factors that affect therapy options. Dr. Preeshagul also provides an update on the latest research and clinical trials.
Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul.
Download Program Resource Guide
See More From INSIST! Lung Cancer
Transcript:
Katherine Banwell:
Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’ll discuss the latest advances in non-small cell lung cancer care as part of our Insist series, which encourages patients to play an active role and insist on better care. Before we get into the discussion, please remember that this 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 me is Dr. Isabel Preeshagul. Dr. Preeshagul, it’s so good to have you with us. Thank you. Would you introduce yourself?
Dr. Isabel Preeshagul:
Yes. Thank you so much for having me and for the very kind introduction. My name’s Isabel Preeshagul. I am a Thoracic Medical Oncologist at Memorial Sloan Kettering Cancer Center, and it is a huge honor to be here with you today.
Katherine Banwell:
Well, we’re so glad to have you with us. I’d like to start with a question pertaining to our series title, Insist. Why is it essential for patients to collaborate with their providers on care treatment decisions?
Dr. Isabel Preeshagul:
So, collaborating is so important, right? I always tell my patients this is not a dictatorship, right? This is a collaborative effort where I’m here to guide you, but you are the captain of the ship.
You are the one that needs to make all of the decisions, and I’m here to make sure that the ship goes in a smooth direction, so making sure we have open lines of communication that the patients and their caregivers feel comfortable talking to me and my team and also vice versa and that we trust each other. It’s so important because we are going for a marathon, right? We’re not going for a sprint. This is a long-term relationship, whether we’re treating for cure or we’re treating you with palliative intent and it’s treatable but not curable. We’re going to be following with each other for a long time.
Katherine Banwell:
A lung cancer healthcare team, of course, consists of a number of different providers. Would you tell us about the various members on a team?
Dr. Isabel Preeshagul:
Sure. So, there is – there are the people that do the scheduling, that make sure that the CAT scan is scheduled, that the MRI is done, your chemo gets scheduled, all of that. The schedulers are super important and an integral part of our team.
And then we also have our office coordinators that answers the phone calls and passes along the messages and assists with scheduling and sort of sets expectations and is the face of the practice. Then you have an office practice nurse or an oncology practice nurse who is the doctor’s right hand, making sure that the patients get proper chemotherapy teaches, making sure that they understand about possible side effects, risks versus benefits, making sure medications are up to date, assessing symptoms.
They are sort of the front line when it comes to any patient call they’re triaging, and they’re escalating or deescalating. That would be the office practice nurse. And then you have an advanced care practitioner, an APP. You either have a nurse practitioner or a PA that’s working with you that’s sometimes seeing patients independently, sometimes putting chemotherapy orders, you know, really serving as almost as another doctor.
If for some reason there is something that the doctor’s not available to do, the doctor needs in a pinch, or my patients that are almost at long-term follow-up that are doing great that are just kind of coasting, I will share with my NP and make sure that they know her just as well as they know me. And sometimes there’s a fellow or there’s a resident or there’s a med student that’s part of the team as well because see one, do one, teach one. It’s really important to teach those that are coming after you and serve as mentors and really include them in part of the team and part of the decision-making. And then you have the doctor that just kind of oversees everything.
Katherine Banwell:
Of course. How would you define treatment goals for people with lung cancer?
Dr. Isabel Preeshagul:
So, the goal of treatment, I think, is really contingent upon someone’s stage, but it’s also contingent upon what’s important to the patient, right? So, we have patients that are stage I all the way to stage IIIC that we treat with intention to cure.
And patients that have stage IV disease, it’s treatable but not curable. So, I am very transparent with that as long as I have the information to have that discussion. With that being said, there are some patients with stage IIIdisease or stage I disease that don’t really want treatment and want to focus on quality of life. And that’s okay too. And in which case, you know, at some point, their cancer will likely progress. How quickly or when that will happen, we don’t know. Could they pass from something else? It’s possible. But you really need to talk about what’s important to the patient, because it’s not always cut and dry.
Katherine Banwell:
As you mentioned, Dr. Preeshagul, there are several different support members on a team. What would you say to patients or even care partners who can sometimes feel like they’re bothering their healthcare team with their questions and comments?
Dr. Isabel Preeshagul:
So, we do get that concern a lot. And I always say, “I’m here for you 24/7. And, if it’s not me, it’s someone that’s just as qualified to answer your questions no matter what.”
“And I would rather get a phone call at 3:00 a.m. than get a phone call at 9:00 a.m., and you need to go to the hospital right now or God forbid something happened. I get a phone call from someone in the ICU that you went overnight and terrible things happened. So, I want the phone calls to come through to keep you out of the hospital and keep you from going south. So, call me.” And I never try to – I don’t try to outline contingency plans or criteria of what would warrant a call, because then you end up getting in trouble.
I always just tell my patient, “Think about how you’re feeling now in front of me. If you’re feeling any different than how you feel at this very moment, call me.”
Katherine Banwell:
Good advice. I’d like to turn to the clinical side of non-small cell lung cancer. What tests help you identify the type and stage of lung cancer?
Dr. Isabel Preeshagul:
Obviously, you need a CAT scan. You need a CAT scan of the chest, abdomen, pelvis, and you need an MRI brain and a PET scan.
Those are really the gold standards for determining clinical staging. In regards to pathologic staging, it’s really important to have tissue samplings. So, you biopsy a site of disease that’s concerning to you. If it looks like there’s only disease in the chest, you want to biopsy the site where there’s the tumor, and then you talk with your thoracic surgery or pulmonary team to determine the best way to sample the mediastinum for full staging.
Katherine Banwell:
Why is an accurate diagnosis so important?
Dr. Isabel Preeshagul:
So, an accurate diagnosis is so important because lung cancer is by no means black and white anymore. There are so many histologic subtypes that we are learning about. There are so many different molecular drivers that we are learning about. So, making sure you have the right diagnosis, full and next-generation sequencing testing, all of the imaging that you need could really make or break your treatment plan.
Katherine Banwell:
Dr. Preeshagul, let’s talk about biomarker testing. How is biomarker testing for lung cancer different from hereditary genetic testing?
Dr. Isabel Preeshagul:
So, we do do hereditary genetic testing for lung cancer patients as well. So, I think let’s backtrack a little bit. When you’re doing on a patient, there’s germline mutations and there’s somatic mutations. And germline mutations are mutations that you might get from Mom and Dad that they got from their parents and so on and so forth that you could give to your children or your brother and sister or whatever. So, that’s germline testing that could be passed along.
That would be like BRCA or any other APC gene, but we are learning more and more that there are mutations in lung cancer that do have a hereditary aspect to them. So, we are learning now that while we do somatic testing, which is to find a mutation that just spontaneously happened in your tumor all on its own, it’s really important to pair that with germline testing to make sure that there isn’t some kind of heritable mutation that’s also driving this lung cancer.
Katherine Banwell:
You mentioned hereditary genetic testing. Should family members of people with lung cancer undergo genetic testing then just to be reassured?
Dr. Isabel Preeshagul:
So, if there is a germline mutation, then they should – the family members should be referred to a geneticist to have that discussion.
Katherine Banwell:
What are common lung cancer biomarkers?
Dr. Isabel Preeshagul:
So, we have nine biomarkers within approval right now, but there are so many. There’s more than I could even talk about today. But some of the more common ones are EGFR, ALK, ROS1, MET exon 14. You have KRAS, KRAS-G12C, which is a newer one. We have NTRK. We have RET. The list goes on, HER2. I could talk for – there’s not enough time on this Zoom video to talk about all of the mutations. But there are nine mutations with approvals as of now to date, this very moment. That could change tomorrow.
Katherine Banwell:
Of course, it could. How do biomarkers in lung cancer affect treatment options for lung cancer patients?
Dr. Isabel Preeshagul:
So, it used to only be in stage IV, but now we are learning that biomarker testing is really important from the get-go because we have induction or neoadjuvant protocols that are looking at giving targeted therapy before patients go to surgery.
We know that there’s FDA approval for patients to get targeted therapy after surgery, and there’s a survival advantage there. So, make sure that you have next-generation sequencing testing regardless of your stage.
Katherine Banwell:
Okay. That’s good advice. So, we’ve heard how testing and a patient’s individual disease can lead to more targeted options. And you just mentioned targeted therapies. How do they work?
Dr. Isabel Preeshagul:
So, there’s many different targeted therapies that we have. Some of given as an infusion. For HER2, for example, we have TDXD, and we have T-DM1. TDXD is the only drug that’s FDA-approved in this setting. There are clinical trials looking at T-DM1. For EGFR Exon 20, we have another infusional drug called amivantamab (Rybrevant). For EGFR Exon 19 and Exon 21, we have a pill called osimertinib (Tagrisso). For KRAS, there’s a pill. For most of the driver alterations, it’s a pill, but some of them it does require infusional therapy.
But these are therapies that are targeted at the cells that harbor that mutation.
Katherine Banwell:
Let’s turn to immunotherapy. What is it, and how does it work?
Dr. Isabel Preeshagul:
So, immunotherapy is basically teaching your body to recognize cancer as foreign. So, when you have – I always kind of use this hand model. So, basically, a normal cell has, let’s say, three prongs. And then sometimes what happens is cancer will grow a marker called PD-L1 that makes it hide from the immune system. So, the body thinks that this is a normal cell. So, what immunotherapy does is it comes up and it sort of puts a cap on that PD-L1 so that the cell looks foreign again and the body can attack that cell and get rid of it. So, it’s almost like ramping up your immune system to recognize that marker and get rid of that cell.
Katherine Banwell:
What is the regimen for immunotherapy, and how often is treatment administered?
Dr. Isabel Preeshagul:
So, immunotherapy is approved in the neoadjuvant setting, which means before chemotherapy. It’s approved after chemotherapy, and it’s approved in the stage IV setting. There are many different regimens and many different dosings and many different drugs. But it’s typically given in your veins, either once every three weeks or once every four weeks for a certain amount of time. If it’s given in a curative setting and it’s given indefinitely or until there’s disease progression or intolerance in the stage IV setting.
Katherine Banwell:
Okay. Let’s touch upon the side effects of these types of treatment. You’ve mentioned that there are so many, but what are some of the major side effects, and how are they managed?
Dr. Isabel Preeshagul:
Side effects of immunotherapy can include pneumonitis, which is inflammation of the lungs, any kind of endocrinopathy like issues with your thyroid, issues with your pancreas like diabetes.
It can cause colitis, which is diarrhea, inflammation of the colon, hepatitis, inflammation of the liver. It can cause cerebritis, inflammation of the brain. It can cause arthritis or arthralgias, inflammation of the bones. And it can also cause rash and fatigue.
Typically, if it’s the thyroid, it’s managed with thyroid replacement hormone or a drug that would calm down the thyroid if it’s overactive. Pneumonitis is steroids. Hepatitis is sometimes treated with steroids. Colitis, steroids typically. Steroids usually come somewhere in there, usually not with the endocrinopathies, but the other itis’s, it’s typically – we start with steroids and go up from there. And the goal is to really recognize these toxicities before they become a problem and just at the glimmer of them just starting.
Katherine Banwell:
So, would you consider these treatments to be personalized medicine then?
Dr. Isabel Preeshagul:
So, it’s personalized in the sense that if someone has a high PD-L1 expression, there may be some data to demonstrate that they may benefit from immunotherapy or have a response. If someone can’t tolerate chemotherapy or is not interested in chemotherapy or has other reasons that may preclude them from getting it, it might be reasonable. So, in that sense, it is considered personalized.
Katherine Banwell:
How would you define personalized medicine?
Dr. Isabel Preeshagul:
To me, personalized medicine takes into account the biologic makeup of a patient’s disease like if they have a mutation and what their PD-L1 status is, what the histologic makeup of it. What’s their stage? And then, on the other hand, what’s important to that patient? If they’re a tailor, you want to make sure you’re not giving them a medication that’s going to cause neuropathy, so they can’t use their hands.
If they enjoy playing the harp or the piano, same thing. If their goal is to continue to run marathons, you may want to avoid something that’s going to cause inflammation of the lungs and risk them for pneumonitis. Tailoring to make sure that the treatment is part of their life but does not become their life.
Katherine Banwell:
If the test results don’t reveal one of the biomarkers you’ve been talking about, what other treatments are available?
Dr. Isabel Preeshagul:
So, if I don’t have an FDA approval, then sometimes we look to see if there is a clinical trial in our early phase drug development program, and we talk about a clinical trial. If there’s no clinical trial and I don’t have an FDA approval, then we have to talk about what options are considered standard of care and how to make that work into the patient’s lifestyle.
Katherine Banwell:
What about surgery? When is it used?
Dr. Isabel Preeshagul:
Surgery is typically used in the curative setting with early-stage disease. We’re really trying to give patients some kind of chemotherapy or some kind of treatment before they go to surgery. It’s shown to improve outcomes. It just gives us a en vivo view of how the tumor will respond to the treatment. So, we typically use surgery in the curative setting. And, at times, it’s appropriate to use surgery for a metastasectomy when you have one little site that’s growing. Sometimes after a tumor board discussion, it might be reasonable to resect that area.
Katherine Banwell:
Is radiation still used?
Dr. Isabel Preeshagul:
Same thing. It can be used in the curative setting, typically for patients with stage IIIB or stage IIIC disease and combined with chemotherapy patients that are not considered surgical candidates, or it’s used in the palliative setting when patients have painful metastases.
Katherine Banwell:
Would you define the B and C? You’ve mentioned that a couple of times.
Dr. Isabel Preeshagul:
Yeah.
Katherine Banwell:
We’re used to hearing Stage 1, 2, 3, 4. But what’s a stage IIIB and a stage IIIC?
Dr. Isabel Preeshagul:
Yeah. Sure. Sure. So, it does get a little bit into the weeds here about the size of the tumor and the amount of lymph nodes and location of the lymph nodes. But basically, stage IIIA is considered resectable. That means – that could be the size of the tumor with no lymph nodes, or it could be a smaller tumor with a lymph node on the same side as the disease. Stage IIIB would be a lymph node right underneath the windpipe at the station 7. And stage IIIB also includes lymph nodes that have crossed over to the contralateral side. And stage IIIC would be lymph nodes that are maybe up at the contralateral supraclavicular space.
Katherine Banwell:
Okay. Do treatment options change if the lung cancer returns?
Dr. Isabel Preeshagul:
Yes, they do change depending on if this is the same tumor type that’s come back. It’s typically a different treatment algorithm, yeah.
Katherine Banwell:
Okay. And should biomarker testing be done again if a relapse occurs?
Dr. Isabel Preeshagul:
100 percent. Because it guides everything about a patient’s treatment. It’s super important.
Katherine Banwell:
Okay. What are you excited about right now in lung cancer research?
Dr. Isabel Preeshagul:
I am excited and overwhelmed by the fact that we have so many approvals and so much exciting data that was just presented at ASCO and World Lung and ESMO that it’s next to impossible to keep up. And I’m happy that we have that problem, and I’m happy that the patients have – there’s a spotlight on lung cancer when we were in the shadows. And now, I think we have the spotlight.
And all of these approvals, you know, with it being Lung Cancer Awareness Month as well, I think is just so important. Just to make sure that we get the knowledge of these new approvals out there though, that is another struggle.
Katherine Banwell:
Well, are there any current clinical trials that look promising to you?
Dr. Isabel Preeshagul:
Yeah, I think there are many clinical trials. In the induction setting, there was some data that was just presented on ALINA looking at adjuvant alectinib (Alecensa). We just had a – we have approval for adjuvant osimertinib (Tagrisso) and the ADAURA trial.
But we are learning more and more that as these targeted therapies have approval in stage IV, we’re trialing them in stage III, and then we’re going to trial them in earlier stages and earlier settings. So, this has been the pattern of how drugs get approved. So, yes, there’s lots of exciting data coming through.
Katherine Banwell:
That’s excellent. Can you talk about antibody drug conjugates and where they fit into lung cancer care?
Dr. Isabel Preeshagul:
Yeah. That’s a great question. I don’t think anyone knows the answer as to where they fit in just yet.
We have probably over 300 antibody drug conjugates that are in development right now. And one of the more common ones that we use is trastuzumab deruxtecan (Enhertu), or TDXD, which is used in patients that harbor HER2 alterations in the stage IV lung cancer setting. It is basically almost like a Trojan horse. So, you have this antibody.
It’s typically IgG1, immunoglobulin. And then you have a linker, and then at the end of that linker is the warhead or the chemotherapy agent. So, the antibody comes in towards the cancer cell looking very innocent. It binds to the cancer cell. And, once it binds, then everyone inside the Trojan horse or this warhead rush into the cell and get to do its damage. So, it’s a totally different mechanism. We’re trying to outsmart some of the bypass mechanisms that cancer cells develop. And this may be the new wave, but stay tuned, more to come.
Katherine Banwell:
Right. So, it’s promising. How can patients find out more about current clinical trials?
Dr. Isabel Preeshagul:
So, you can always ask your healthcare practitioner if there are any clinical trials at the institution that you’re at, but clinicaltrials.gov has all the clinical trials that are available nationally and internationally.
You just type in your disease type. You can type in a couple keywords, EGFR maybe or ROS1 or stage IV, something along those lines, and then it should populate a list of clinical trials and what institutions have them open, if they’re still accruing or if they’re not, and a contact on that trial.
Katherine Banwell:
If a patient is interested in a clinical trial, what kinds of questions should they be asking their healthcare about the trial?
Dr. Isabel Preeshagul:
So, the first question to ask is, “Do we have any clinical trials that are appropriate for me?” If the answer is yes, “Are they appropriate for me now, or are they appropriate for me if what I’m on right now is not working?”
So, trying to figure out where that will be, and if they are appropriate for you now, how can I get evaluated, and how can we get things underway?
Katherine Banwell:
Yeah. What would you say to patients who are interested in participating in a clinical trial, but they’re nervous about it?
Dr. Isabel Preeshagul:
I think one thing that I love about being on a clinical trial is that there are more eyes are on you, because we are looking to get something approved, and we are just watching every single little granular detail. In a way, it’s almost like you’re being more micromanaged than if you were on standard of care because of just how many stops and checks there are, how many eyes are looking at your labs after the doctor and the nurse and the nurse practitioner, and the fellow take a look at everything. It’s 10 other people. So, it’s almost like it’s extra safe because of all of that. It’s exciting because you are hopefully getting tomorrow’s treatment today, right?
You’re trailblazing the way for other people after you. So, I think it’s exciting, but, of course, it’s nerve-wracking. It’s something new. You don’t know if it’s going to work. But I have to believe that the way that clinical trials are designed now and the clinical trials that we choose to open here, we really hope are going to be pushing the space forward.
Katherine Banwell:
Yeah. I’d like to get to a few questions that we received from audience members prior to the program. How do you help a family member that is an overwhelmed caregiver but refuses help? Any tips on how to provide support to this person?
Dr. Isabel Preeshagul:
I mean, I think we see caregiver burnout thousands of times a day, unfortunately, and the first thing is knowing how to recognize it. And the second most important thing is taking the time away from the visit with the patient to address the burnt-out caregiver, because there is not enough time in any visit to ever – there’s never enough time in my mind to spend with a patient.
I’m always pulled in a thousand different directions. And I think we all feel that. But taking the appropriate time to sit down and to say, “Hey. Listen. I recognize that you’re burnt out. I can see it. Who is in your corner helping you?” And just directing focus away from the patient just for a moment and to really focus on that caregiver and to rely on the social work team and the case manager and the support groups that your institution may have and to make sure that they know about those resources.
Katherine Banwell:
Yeah. Here’s another question we received. “Can you share more information regarding treatments available for stage IV lung cancer and their side effects?”
Dr. Isabel Preeshagul:
It depends on if this is non-small cell or small cell. It depends on if you have a driver alteration or not. So, I think that is a little bit challenging to talk about in just one session. But basically, you’re probably looking at some kind of targeted therapy if you have a mutation versus standard of care if you don’t have a targeted mutation versus a clinical trial. And I think those are kind of like the big baskets.
Katherine Banwell:
When is a second opinion necessary? Dr. Isabel Preeshagul: A second opinion is necessary anytime you want a second opinion.
Dr. Isabel Preeshagul:
There is no right or wrong time, any time. You’re just not jiving with your oncologist after the first day you met them, second opinion. You’re at the end of the line and you really want toknow more, second opinion. You’ve met two other doctors. You’re not jiving, third opinion. It’s always appropriate anytime you want.
Katherine Banwell:
So, the patient shouldn’t feel obligated to stay with that one provider?
Dr. Isabel Preeshagul:
Never. Never, never, never, never, never. No. Please don’t feel that way. There are no hard feelings. And, if there are, that’s not the right oncologist for you. It needs to feel like a perfect friendship. And, if it’s not that, it’s not the right thing.
Katherine Banwell:
Before we close, Dr. Preeshagul, I’d like to get your final thoughts. What would you say to the audience about the future of lung cancer care and treatment?
Dr. Isabel Preeshagul:
I do think that the future is bright because, as I mentioned, there is now this light that is shining in the lung cancer space. And things are getting approved. and discoveries are getting made faster than we can even keep up, which is exciting and overwhelming and daunting. But I am happy that, finally, this space is taking off, so I feel optimistic.
Katherine Banwell:
Okay. All right. Well, I wanna thank you so much for taking the time to join us today, Dr. Preeshagul.
Dr. Isabel Preeshagul:
Thank you so much for having me. These were wonderful questions, and I look forward to many more discussions with you. Thank you.
Katherine Banwell:
And thank you to all of our partners. To learn more about lung cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today.
Non-Small Cell Lung Cancer Treatment Options | Personalizing Therapy
Non-Small Cell Lung Cancer Treatment Options | Personalizing Therapy from Patient Empowerment Network on Vimeo.
How does the presence of biomarkers impact lung cancer treatment options? Lung cancer specialist Dr. Isabel Preeshagul discusses how test results may influence treatment options and aid in personalizing lung cancer therapy.
Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul.
See More From INSIST! Lung Cancer
Related Resources:
An Expert Explains Predictive Biomarker Testing for Lung Cancer |
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|
Transcript:
Katherine Banwell:
How do biomarkers in lung cancer affect treatment options for lung cancer patients?
Dr. Isabel Preeshagul:
So, it used to only be in stage IV, but now we are learning that biomarker testing is really important from the get-go because we have induction or neoadjuvant protocols that are looking at giving targeted therapy before patients go to surgery.
We know that there’s FDA approval for patients to get targeted therapy after surgery, and there’s a survival advantage there. So, make sure that you have next-generation sequencing testing regardless of your stage.
Katherine Banwell:
Okay. That’s good advice. So, we’ve heard how testing and a patient’s individual disease can lead to more targeted options. And you just mentioned targeted therapies. How do they work?
Dr. Isabel Preeshagul:
So, there are many different targeted therapies that we have. Some of given as an infusion. For HER2, for example, we have TDXD, and we have T-DM1. TDXD is the only drug that’s FDA-approved in this setting. There are clinical trials looking at T-DM1. For EGFR Exon 20, we have another infusional drug called amivantamab-vmjw (Rybrevant). For EGFR Exon 19 and Exon 21, we have a pill called osimertinib (Tagrisso). For KRAS, there’s a pill. For most of the driver alterations, it’s a pill, but some of them it does require infusional therapy. But these are therapies that are targeted at the cells that harbor that mutation.
Katherine Banwell:
Let’s turn to immunotherapy. What is it, and how does it work?
Dr. Isabel Preeshagul:
So, immunotherapy is basically teaching your body to recognize cancer as foreign. So, when you have – I always kind of use this hand model. So, basically, a normal cell has, let’s say, three prongs. And then sometimes what happens is cancer will grow a marker called PD-L1 that makes it hide from the immune system. So, the body thinks that this is a normal cell. So, what immunotherapy does is it comes up and it sort of puts a cap on that PD-L1 so that the cell looks foreign again and the body can attack that cell and get rid of it. So, it’s almost like ramping up your immune system to recognize that marker and get rid of that cell.
Katherine Banwell:
What is the regimen for immunotherapy, and how often is treatment administered?
Dr. Isabel Preeshagul:
So, immunotherapy is approved in the neoadjuvant setting, which means before chemotherapy. It’s approved after chemotherapy, and it’s approved in the stage IV setting. There are many different regimens and many different dosings and many different drugs. But it’s typically given in your veins, either once every three weeks or once every four weeks for a certain amount of time. If it’s given in a curative setting and it’s given indefinitely or until there’s disease progression or intolerance in the stage IV setting.
Katherine Banwell:
Okay. Let’s touch upon the side effects of these types of treatment. You’ve mentioned that there are so many, but what are some of the major side effects, and how are they managed?
Dr. Isabel Preeshagul:
Side effects of immunotherapy can include pneumonitis, which is inflammation of the lungs, any kind of endocrinopathy like issues with your thyroid, issues with your pancreas like diabetes.
It can cause colitis, which is diarrhea, inflammation of the colon, hepatitis, inflammation of the liver. It can cause cerebritis, inflammation of the brain. It can cause arthritis or arthralgias, inflammation of the bones. And it can also cause rash and fatigue.
Typically, if it’s the thyroid, it’s managed with thyroid replacement hormone or a drug that would calm down the thyroid if it’s overactive. Pneumonitis is steroids. Hepatitis is sometimes treated with steroids. Colitis, steroids typically. Steroids usually come somewhere in there, usually not with the endocrinopathies, but the other itis’s, it’s typically – we start with steroids and go up from there. And the goal is to really recognize these toxicities before they become a problem and just at the glimmer of them just starting.
Katherine Banwell:
So, would you consider these treatments to be personalized medicine then?
Dr. Isabel Preeshagul:
So, it’s personalized in the sense that if someone has a high PD-L1 expression, there may be some data to demonstrate that they may benefit from immunotherapy or have a response. If someone can’t tolerate chemotherapy or is not interested in chemotherapy or has other reasons that may preclude them from getting it, it might be reasonable. So, in that sense, it is considered personalized.
Katherine Banwell:
How would you define personalized medicine?
Dr. Isabel Preeshagul:
To me, personalized medicine takes into account the biologic makeup of a patient’s disease like if they have a mutation and what their PD-L1 status is, what the histologic makeup of it. What’s their stage? And then, on the other hand, what’s important to that patient? If they’re a tailor, you want to make sure you’re not giving them a medication that’s going to cause neuropathy, so they can’t use their hands.
If they enjoy playing the harp or the piano, same thing. If their goal is to continue to run marathons, you may want to avoid something that’s going to cause inflammation of the lungs and risk them for pneumonitis. Tailoring to make sure that the treatment is part of their life but does not become their life.
What Essential Testing Reveals About Your Non-Small Cell Lung Cancer
What Essential Testing Reveals About Your Non-Small Cell Lung Cancer from Patient Empowerment Network on Vimeo.
What do lung cancer test results reveal to your healthcare team about your disease? Dr. Isabel Preeshagul provides an overview of essential testing for lung cancer and explains the difference between germline and somatic mutations.
Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul.
See More From INSIST! Lung Cancer
Related Resources:
|
Non-Small Cell Lung Cancer Treatment Options | Personalizing Therapy |
Non-Small Cell Lung Cancer Treatment | Clinical Trials and Research Updates |
Transcript:
Katherine Banwell:
I’d like to turn to the clinical side of non-small cell lung cancer. What tests help you identify the type and stage of lung cancer?
Dr. Isabel Preeshagul:
Obviously, you need a CAT scan. You need a CAT scan of the chest, abdomen, pelvis, and you need an MRI brain and a PET scan.
Those are really the gold standards for determining clinical staging. In regards to pathologic staging, it’s really important to have tissue samplings. So, you biopsy a site of disease that’s concerning to you. If it looks like there’s only disease in the chest, you want to biopsy the site where there’s the tumor, and then you talk with your thoracic surgery or pulmonary team to determine the best way to sample the mediastinum for full staging.
Katherine Banwell:
Why is an accurate diagnosis so important?
Dr. Isabel Preeshagul:
So, an accurate diagnosis is so important, because lung cancer is by no means black and white anymore. There are so many histologic subtypes that we are learning about. There are so many different molecular drivers that we are learning about. So, making sure you have the right diagnosis, full and next-generation sequencing testing, all of the imaging that you need could really make or break your treatment plan.
Katherine Banwell:
Dr. Preeshagul, let’s talk about biomarker testing. How is biomarker testing for lung cancer different from hereditary genetic testing?
Dr. Isabel Preeshagul:
So, we do do hereditary genetic testing for lung cancer patients as well. So, I think let’s backtrack a little bit. When you’re doing on a patient, there are germline mutations and there are somatic mutations. And germline mutations are mutations that you might get from Mom and Dad that they got from their parents and so on and so forth that you could give to your children or your brother and sister or whatever. So, that’s germline testing that could be passed along.
That would be like BRCA or any other APC gene, but we are learning more and more that there are mutations in lung cancer that do have a hereditary aspect to them. So, we are learning now that while we do somatic testing, which is to find a mutation that just spontaneously happened in your tumor all on its own, it’s really important to pair that with germline testing to make sure that there isn’t some kind of heritable mutation that’s also driving this lung cancer.
Katherine Banwell:
You mentioned hereditary genetic testing. Should family members of people with lung cancer undergo genetic testing then just to be reassured?
Dr. Isabel Preeshagul:
So, if there is a germline mutation, then they should – the family members should be referred to a geneticist to have that discussion.
Katherine Banwell:
What are common lung cancer biomarkers?
Dr. Isabel Preeshagul:
So, we have nine biomarkers within approval right now, but there are so many. There’s more than I could even talk about today. But some of the more common ones are EGFR, ALK, ROS1, MET exon 14. You have KRAS, KRAS-G12C, which is a newer one. We have NTRK. We have RET. The list goes on, HER2. I could talk for – there’s not enough time on this Zoom video to talk about all of the mutations. But there are nine mutations with approvals as of now to date, this very moment. That could change tomorrow.
