Tag Archive for: biomarkers

Disease Monitoring: Is My AML Treatment Working?

Disease Monitoring: Is My AML Treatment Working? from Patient Empowerment Network on Vimeo.

Dr. Eytan Stein explains how AML treatment effectiveness is monitored and why it’s essential for patients to report any symptoms or side effects to their healthcare team.

Dr. Eytan Stein is a hematologist oncologist at Memorial Sloan Kettering Cancer Center and serves as Director of the Program for Drug Development in Leukemia in Division of Hematologic Malignancies. Learn more about Dr. Stein, here.

See More from Thrive AML

Related Resources:

Considerations When Choosing an AML Treatment

What Are the Phases of AML Therapy

What Are Current and Emerging AML Treatment Approaches?


Transcript:

Katherine Banwell:

Once treatment has begun, Dr. Stein, how do you know if it’s working?  

Dr. Eytan Stein:

So, that’s a good question. So, the good thing about acute myeloid leukemia when it comes to understanding what’s going on, you know, it’s a disease of the bone marrow cells. And we do bone marrow biopsies to see how things are doing. But no one likes a bone marrow biopsy. It can be a somewhat uncomfortable procedure.  

Katherine Banwell:

How often would a patient need to have a biopsy? 

Dr. Eytan Stein:

Yeah, so they have bone marrow biopsies at diagnosis, and then they often will have bone marrow biopsies two weeks to a month later.  

And then, if they’re in remission, basically any time you think if you want to check to see if they’re in remission or if you suspect the patient is relapsing. Then, you would do a bone marrow biopsy. But what I was getting at is that but you have blood. And the blood is kind of like the bellwether of what’s going on in the bone marrow.  

So, the analogy I use for my patients is, you know, when you’re driving your car and you have – you know, you don’t open the hood every day to make sure the car is running okay. You know, you’re driving your car, and if your car starts making a funny clinking sound, that’s when you open the hood.  

So, the blood is like the clinking sound. If you see something going wrong in the blood, that’s when you know you’ve got to open the hood and look under the hood. If the car is running just fine and you don’t see anything wrong in the blood, using the analogy, maybe you don’t need to do a bone marrow biopsy. 

Katherine Banwell:

What if a treatment isn’t working? What if it stops working or if the patient relapses? What do you do then? 

Dr. Eytan Stein:

Yeah, so when a patient relapses, which unfortunately happens more than we want it to, it’s important number one to do another bone marrow biopsy and at that point, do that mutational testing again because the mutations that are present at the time of diagnosis are not necessarily going to be present at the time of relapse, and sometimes, a new mutation might occur at the time of relapse.  

And again, what that mutational profile shows can help determine what the next best treatment for the patient is. There might be standard-of-care therapies. More chemotherapy might be recommended.  

When a patient relapses, I usually – excuse me – try to get them on a clinical trial because that’s the point where I think clinical trial drugs really have potentially major benefit for the patients, to help get them back into remission. 

How Do Gene Mutations Affect AML Treatment Choices?

How Do Gene Mutations Affect AML Treatment Choices? from Patient Empowerment Network on Vimeo.

Dr. Eytan Stein shares why AML patients should undergo molecular testing when choosing a treatment approach, explaining how targeted therapy works to treat AML patients who have specific genetic mutations.

Dr. Eytan Stein is a hematologist oncologist at Memorial Sloan Kettering Cancer Center and serves as Director of the Program for Drug Development in Leukemia in Division of Hematologic Malignancies. Learn more about Dr. Stein, here.

See More from Thrive AML

Related Resources:

Considerations When Choosing an AML Treatment

Managing Your Oral AML Treatment | Tips for Staying on Schedule

What Are Current and Emerging AML Treatment Approaches?


Transcript:

Katherine Banwell:

Why is identification of genetic markers essential before choosing treatment?  

Dr. Eytan Stein:

Because when you know the genetic markers, you can target the genetic abnormalities, sometimes with specific targeted therapies, with therapies that fit like a key in a specific lock.  

And those targeted therapies have been shown, in some cases, to improve the survival of the patients, without much cost, without much toxicity. So, I’ll give you an example of this.  

There is a very common genetic abnormality in patients with acute myeloid leukemia called the FLT3 or FLT3 mutation. When you have that mutation, there is a targeted therapy that targets the FLT3 mutation called midostaurin (Rydapt), and it’s been shown in a very large clinical trial that the addition of the targeted FLT3 inhibitor midostaurin in combination with chemotherapy leads to better overall survival than chemotherapy alone.  

So, you need to know that information because you want to give your patient the best chance at beating the disease. And that’s why it’s also important to try to get this information back quickly. You know, no one wants to be sitting around waiting for four weeks to find out if they’ve got a specific mutation. And we’ve gotten better. I think medical centers generally have gotten better at getting this mutational information back to their doctors relatively quickly. 

Katherine Banwell:

Does every patient get this standard testing? 

Dr. Eytan Stein:

It is – does everyone get it? I don’t know. But “Should everyone get it?” is, I think, the important question. Yes, everyone should get this testing.  

It is incorporated into the NCCN and National Comprehensive Cancer Network and European Leukemia Net guidelines. It is important not only because you can think about targeted therapies, but it is also important for prognostic reasons, meaning that certain mutations lead to a higher risk of relapse, and those mutations in a patient might lead me to recommend a stem cell transplant, which is sort of the most intensive thing we can do to help prevent a relapse, while other mutations, which might be “favorable”, in quotes, they might lead me not to recommend a stem cell transplant.  

So, I think this mutational testing is the standard of care and should be done in every patient with newly diagnosed acute myeloid leukemia.  

What Are Current and Emerging AML Treatment Approaches?

What Are Current and Emerging AML Treatment Approaches? from Patient Empowerment Network on Vimeo.

AML Expert Dr. Eytan Stein provides an overview of current and emerging treatment approaches for people living with AML.

Dr. Eytan Stein is a hematologist oncologist at Memorial Sloan Kettering Cancer Center and serves as Director of the Program for Drug Development in Leukemia in Division of Hematologic Malignancies. Learn more about Dr. Stein, here.

See More from Thrive AML

Related Resources:

Considerations When Choosing an AML Treatment

How Do Gene Mutations Affect AML Treatment Choices?

Disease Monitoring: Is My AML Treatment Working?


Transcript:

Katherine Banwell:

What are the treatment types available to AML patients? You mentioned chemotherapy. What else is there? 

Dr. Eytan Stein:

Yeah, so if I was having this discussion with you, even when I first started my career back in 2013, all I would’ve been talking to you about was induction chemotherapy and maybe a lower-dose chemotherapy called hypomethylating agents.  

I think one thing that really needs to be recognized is that the advances we’ve made for the treatment of acute myeloid leukemia, over the past 10 years, have been just remarkable. We’ve had a number up to nine drug approvals over the past 10 years, and those therapies fall into the following categories.  

We now have therapies outside the strong induction consolidation we talked about. We have therapies such as targeted therapies that target specific gene mutations that are present in patients with acute myeloid leukemia. Those are often oral therapies that patients can take at home. And we have very effective therapies for older patients who usually can’t handle the side effects of induction chemotherapy. That’s the combination of a type of drug called a hypomethylating agent with a very, very powerful targeted drug called a BCL-2 inhibitor.  

One of those drugs, that drug is called venetoclax. That’s the one that’s FDA-approved. And the combination of those hypomethylating agents and venetoclax, has really changed the paradigm for how we treat older patients with acute myeloid leukemia, led to many patients who have been able to live much longer than they would have before this therapy came about.  

You know, there are other therapies that are in development, but I don’t know if we’ll end up talking about that a little bit later. But there are therapies such as immunotherapy, which has gotten a lot of press for other kinds of cancers, like one cancer called the rectal cancer, that aren’t yet approved for acute myeloid leukemia but are being developed for acute myeloid leukemia.   

So, the future of acute – the current treatments for acute myeloid leukemia are dramatically better than they were 10 years ago, and I would anticipate that we’re going to continue to see these kind of advances over the next 10 years.  

Katherine Banwell:

What about stem cell transplant? Who might be right for that? Who might be eligible? 

Dr. Eytan Stein:

Yeah, so let’s go back to the discussion a little bit about consolidation chemotherapy. So, when you have a patient that gets induction chemotherapy or gets any therapy – it doesn’t have to be chemotherapy – to put their disease into remission, for a large group of patients, we think that the best way to cure their disease is to do something called a stem cell transplant.  

So, what’s a stem cell transplant? What it is not is like a heart transplant or a liver transplant, which patients often don’t realize.  

So, it’s not a procedure where an organ is being transplanted through a surgical procedure. What it is is it’s acknowledging that the cause of acute myeloid leukemia is that the most primitive cells in the bone marrow, called the stem cells, are the cause of the disease. And the chemotherapies that we give patients to get them into remission don’t always eradicate those bad stem cells.  

So, what we’re able to do once a patient is in remission is we try to get them new stem cells. How do you get a patient new stem cells? Well, you go to a donor, and there’s a donor bank of people who have volunteered to donate stem cells to patients with acute myeloid leukemia. You go to the donor bank, and then you give chemotherapy to the patient to sort of wipe out their bad stem cells, and then you give them new stem cells that will hopefully permanently eradicate the disease. 

What ends up happening is that a large group of patients with acute myeloid leukemia end up being referred for a stem cell transplant. The reason is twofold. You know, it used to be – I keep talking about the past. I’m getting older, and so now I can talk about the past.  

Yeah. So, it used to be that stem cell transplants were really reserved to people less than 65 years old.  

But our advances in our ability to do stem cell transplants has allowed for us to now successfully do stem cell transplants on patients, even into their upper 70s and sometimes even at the age of 80.  

Katherine Banwell:

Where do clinical trials fit in to all of this? 

Dr. Eytan Stein:

Ah. So, clinical trials are extraordinarily important for a variety of reasons. Clinical trials are important because the only way we make advances on a societal level in the treatment of acute myeloid leukemia is by patients who are willing to participate in clinical trials. All of the – because these are trials that are testing new therapies with the goal of improving the survival and the quality of life of patients with acute myeloid leukemia. All these drugs I just talked about that have been approved over the past 10 years, they never would’ve been approved if patients hadn’t agreed to participate in clinical trials. So, that’s something that’s number one that’s very important.  

But on a – forget the societal level for a second. On a patient-specific level, a clinical trial can potentially benefit a patient because it offers a patient access to a new, exciting therapy that may really help in improving their outcome of having acute myeloid leukemia.  

Katherine Banwell:

Yeah. You mentioned emerging therapies. What are some of those? 

Dr. Eytan Stein:

Oh, there’s so many. So, it’s hard to talk about all of them, but I think there are targeted therapies – I think if you sort of break them up into sort of broad buckets, there are new targeted therapies that are being developed for subsets of patients with acute myeloid leukemia. One of the ones I’ve been working on pretty heavily over the past few years is a kind of drug called a menin inhibitor. This is an oral medication that is given to patients of acute myeloid leukemia who have certain genetic abnormalities, specifically either a mutation in a gene called NPM1, or a what is called a rearrangement in a gene called MLL.  

So, that’s a group of – that menin inhibition seems to be extraordinarily effective in treating patients, at least from the early data, for those specific subtypes of acute leukemia.  

The other therapies that are really getting a lot of play now are the immunotherapies, which I mentioned a second ago. There are immunotherapies that work to – called bispecific immunotherapies where what happens is it works to harness the immune system to kill the cancer cells. You may have heard a lot about CAR T-cell therapy, which is another way of harnessing the immune system and engineering immune cells to target acute myeloid leukemia cells. And the other thing I want to point out is that even if you don’t have a new therapy against a new target, you can imagine now that we’ve got all these 10 new approved drugs.  

But what we’re trying to figure out – one of the things we’re trying to figure out over the past few years has been what’s the best way to give these new drugs? What kind of combinations can you put them in that might make things even better? Maybe you should give two of those drugs first and then give another drug afterwards. And a lot of the research that’s being done now is being done to understand the best sequencing and combinations of drugs with the drugs that we already have approved. 

Thriving With AML: What You Should Know About Care and Treatment

Thriving With AML: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

What should you consider when choosing acute myeloid leukemia (AML) care and treatment? Dr. Eytan Stein reviews factors that help guide care decisions for AML, discusses the goals of treatment as well as treatment options available, and shares tools for taking an active role in your care.

Dr. Eytan Stein is a hematologist oncologist at Memorial Sloan Kettering Cancer Center and serves as Director of the Program for Drug Development in Leukemia in Division of Hematologic Malignancies. Learn more about Dr. Stein, here.

See More from Thrive AML

Related Resources:

Thriving With AML: What You Should Know About Care and Treatment Resource Guide

Shared Decision-Making, Advice for Partnering With Your AML Team

Which Tests Do You Need Before Deciding on an AML Treatment Path


Transcript:

Katherine Banwell:  

Hello, and welcome. I’m Katherine Banwell, your host for today’s webinar. Today’s program is about how to live and thrive with AML. We’re going to discuss the goals of AML treatment and how you can play an active role in your 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. Eytan Stein. Dr. Stein, welcome. Would you please introduce yourself?  

Dr. Stein:

Thanks so much. My name is Eytan Stein. I work as an attending physician on the leukemia service at Memorial Sloan Kettering Cancer Center in New York City.  

Katherine Banwell:

Excellent. Thank you so much for taking the time to join us today. 

Dr. Stein:

Thank you for having me.  

Katherine Banwell:

Since this webinar is part of Patient Empowerment Network’s Thrive series, I thought we could start by getting your opinion on what you think it means to thrive with AML. 

Dr. Stein:

Yeah, so thriving with AML I think can mean different things to different people. Thriving with AML can mean when you have the disease, really having the fortitude to get through the treatment that you’re being given because sometimes that can be tough.  

And sometimes, it’s not easy. But the people who are thriving are the ones who are able to discuss with their doctors what their treatment is, what the side effects of that treatment might be, how to minimize those side effects, and how to get through that treatment so that not only do they feel better physically but can feel better emotionally and ultimately, hopefully go into a complete remission. 

Katherine Banwell:

Thank you for that, Dr. Stein. I think that helps guide us as we continue this conversation. Getting appropriate AML care is part of thriving, and when we consider treatment options, it’s important to understand the goal of treatment. So, how would you define treatment goals for patients? 

Dr. Stein:

Yeah, so the treatment goals for patients really come in different forms. I think fundamentally what everyone wants is everyone wants to go into a complete remission and be cured of their disease. And certainly, that’s an overarching goal that we aim to achieve with our treatments. But there are other goals that I think are important too to various patient populations, depending on what stage of life they’re in.  

Are they 85 years old or 90 years old and have lived a long, full life? And their goal might be to improve their blood count so they don’t need transfusions so frequently. And they might be able to go to that grandchild or great-grandchild’s wedding or other life event. There are other patients for whom the goal might be, very discreetly, just to get to that next step in their treatment.   

That next step in their treatment might be a bone marrow transplant. The next step in their treatment might be some more therapy. But I think overall as a doctor, our goal is always to do our best to get our patients into a complete remission and cure them while maintaining the best quality of life for our patients.  

Katherine Banwell:

What do you think is the patient’s role in setting treatment goals? 

Dr. Stein:

Well, it’s really important for the doctor to explore the goals of treatment when they first meet with the patient. I don’t think doctors should assume that all patients come into that first visit with the same goals. And what those goals are, I think, may differ a little bit from patient to patient. And it’s really important for the patient to express overtly what their goals are, what they want to achieve from the treatment. You know, I have some patients who come in to me and say, “My goal is to be cured and be alive for the next 30 years” or 40 years or 50 years.  

And I have some patients that come into treatment, and they say, “You know what, I have had a very, very long life, and I just want the best quality I can have for as long as I can possibly have it.” 

Katherine Banwell:

Yeah, that’s great advice. Thank you. As we move into the discussion about treatment for AML, let’s define a couple of terms that are often mentioned in AML care. What is induction therapy?   

Dr. Stein:

Yeah, so induction chemotherapy refers really to a type of chemotherapy that tends to be quite intensive, so strong chemotherapy that patients receive in the hospital setting. That induction chemotherapy typically requires a hospitalization of three to four weeks, sometimes a little bit longer, as the patient gets their treatment during the first week or so and then they’re recovering from the effects of that treatment during the next three weeks in the hospital.  

Katherine Banwell:

Okay. What is consolidation therapy? 

Dr. Stein:

Ah. So, a patient first gets induction chemotherapy. If they achieve a complete remission, so their disease goes away, that’s great. We know their disease seems to be gone. But we also know that patients relapse. So, if patients relapse, it means their disease wasn’t really gone. It’s just that we couldn’t find it. It was hiding somewhere.  

So, consolidation chemotherapy is chemotherapy that is given after a patient is in complete remission in an effort to kill any residual leukemia cells that may be hiding in the body, that we can’t see in our bone marrow biopsies, in an effort to deepen the remission that we’ve achieved during induction.  

Katherine Banwell:

Okay. Are there any other terms that patients should be familiar with? 

Dr. Stein:

There are. You know, there are a lot of other terms that patients should be familiar with. I’ll just touch on one because it can get complicated. We now have for acute myeloid leukemia, a type of therapy that goes beyond induction and consolidation called maintenance therapy.  

Maintenance therapy is when a patient is done with induction, done with consolidation, and the question is, can you give them something that is easy to take, relatively non-toxic, that they can take for a prolonged period of time, to also help prevent relapse? Maintenance therapy has been really a backbone of the treatment of a different kind of leukemia called acute lymphoblastic leukemia, which happens primarily in children for many years. Maintenance therapy is also now a backbone of therapy for a different kind of blood cancer called multiple myeloma. And very recently, only within the past year to two years, we’ve incorporated maintenance therapy for AML for certain groups of patients.  

Katherine Banwell:

Okay. What are the treatment types available to AML patients? You mentioned chemotherapy. What else is there? 

Dr. Stein:

Yeah, so if I was having this discussion with you, even when I first started my career back in 2013, all I would’ve been talking to you about was induction chemotherapy and maybe a lower-dose chemotherapy called hypomethylating agents.  

I think one thing that really needs to be recognized is that the advances we’ve made for the treatment of acute myeloid leukemia, over the past 10 years, have been just remarkable. We’ve had a number up to nine drug approvals over the past 10 years, and those therapies fall into the following categories.  

We now have therapies outside the strong induction consolidation we talked about. We have therapies such as targeted therapies that target specific gene mutations that are present in patients with acute myeloid leukemia. Those are often oral therapies that patients can take at home. And we have very effective therapies for older patients who usually can’t handle the side effects of induction chemotherapy. That’s the combination of a type of drug called a hypomethylating agent with a very, very powerful targeted drug called a BCL-2 inhibitor.  

One of those drugs, that drug is called venetoclax (Venclexta). That’s the one that’s FDA-approved. And the combination of those hypomethylating agents and venetoclax, has really changed the paradigm for how we treat older patients with acute myeloid leukemia, led to many patients who have been able to live much longer than they would have before this therapy came about.  

You know, there are other therapies that are in development, but I don’t know if we’ll end up talking about that a little bit later. But there are therapies such as immunotherapy, which has gotten a lot of press for other kinds of cancers, like one cancer called the rectal cancer, that aren’t yet approved for acute myeloid leukemia but are being developed for acute myeloid.  

So, the future of acute – the current treatments for acute myeloid leukemia are dramatically better than they were 10 years ago, and I would anticipate that we’re going to continue to see these kind of advances over the next 10 years.  

Katherine Banwell:

And we are going to talk further about that in a couple of minutes. What about stem cell transplant? Who might be right for that? Who might be eligible? 

Dr. Stein:

Yeah, so let’s go back to the discussion a little bit about consolidation chemotherapy. So, when you have a patient that gets induction chemotherapy or gets any therapy – it doesn’t have to be chemotherapy – to put their disease into remission, for a large group of patients, we think that the best way to cure their disease is to do something called a stem cell transplant.  

So, what’s a stem cell transplant. What it is not is like a heart transplant or a liver transplant, which patients often don’t realize.  

So, it’s not a procedure where an organ is being transplanted through a surgical procedure. What it is is it’s acknowledging that the cause of acute myeloid leukemia is that the most primitive cells in the bone marrow, called the stem cells, are the cause of the disease. And the chemotherapies that we give patients to get them into remission don’t always eradicate those bad stem cells.  

So, what we’re able to do once a patient is in remission is we try to get them new stem cells. How do you get a patient new stem cells? Well, you go to a donor, and there’s a donor bank of people who have volunteered to donate stem cells to patients with acute myeloid leukemia. You go to the donor bank, and then you give chemotherapy to the patient to sort of wipe out their bad stem cells, and then you give them new stem cells that will hopefully permanently eradicate the disease.  

What ends up happening is that a large group of patients with acute myeloid leukemia end up being referred for a stem cell transplant. The reason is twofold. You know, it used to be – I keep talking about the past. I’m getting older, and so now I can talk about the past.  

Katherine Banwell:

We’ll talk about the future in a couple of minutes. 

Dr. Stein:

Yeah. So, it used to be that stem cell transplants were really reserved to people less than 65 years old.  

But our advances in our ability to do stem cell transplants has allowed for us to now successfully do stem cell transplants on patients, even into their upper 70s and sometimes even at the age of 80.  

Katherine Banwell:

Wow, okay. That’s great. Where do clinical trials fit in to all of this? 

Dr. Stein:

Ah. So, clinical trials are extraordinarily important for a variety of reasons. Clinical trials are important because the only way we make advances on a societal level in the treatment of acute myeloid leukemia is by patients who are willing to participate in clinical trials. All of the – because these are trials that are testing new therapies with the goal of improving the survival and the quality of life of patients with acute myeloid leukemia. All these drugs I just talked about that have been approved over the past 10 years, they never would’ve been approved if patients hadn’t agreed to participate in clinical trials. So, that’s something that’s number one that’s very important.  

But on a – forget the societal level for a second. On a patient-specific level, a clinical trial can potentially benefit a patient because it offers a patient access to a new, exciting therapy that may really help in improving their outcome of having acute myeloid leukemia.  

Katherine Banwell:

Yeah. You mentioned emerging therapies. What are some of those? 

Dr. Stein:

Oh, there’s so many. So, it’s hard to talk about all of them, but I think there are targeted therapies – I think if you sort of break them up into sort of broad buckets, there are new targeted therapies that are being developed for subsets of patients with acute myeloid leukemia. One of the ones I’ve been working on pretty heavily over the past few years is a kind of drug called a menin inhibitor. This is an oral medication that is given to patients of acute myeloid leukemia who have certain genetic abnormalities, specifically either a mutation in a gene called NPM1, or a what is called a rearrangement in a gene called MLL.  

So, that’s a group of – that menin inhibition seems to be extraordinarily effective in treating patients, at least from the early data, for those specific subtypes of acute leukemia.  

The other therapies that are really getting a lot of play now are the immunotherapies, which I mentioned a second ago. There are immunotherapies that work to – called bispecific immunotherapies where what happens is it works to harness the immune system to kill the cancer cells. You may have heard a lot about CAR T-cell therapy, which is another way of harnessing the immune system and engineering immune cells to target acute myeloid leukemia cells. And the other thing I want to point out is that even if you don’t have a new therapy against a new target, you can imagine now that we’ve got all these 10 new approved drugs.  

But what we’re trying to figure out – one of the things we’re trying to figure out over the past few years has been what’s the best way to give these new drugs? What kind of combinations can you put them in that might make things even better? Maybe you should give two of those drugs first and then give another drug afterwards. And a lot of the research that’s being done now is being done to understand the best sequencing and combinations of drugs with the drugs that we already have approved. 

Katherine Banwell:

Great. All patients are different, of course, and what might work for one person might not be appropriate for another. How do you choose which treatment is right for a patient? 

Dr. Stein:

So, it’s an individualized decision. So, what you’re talking to the patient, as we talked about at the very beginning, is you really need to understand the patient’s goals for treatment. You need to understand the anticipated benefit of the treatment that you’re offering and need to understand the side effects of the treatment. 

So, and that sort of becomes the puzzle that you work with the patient at putting together. That is how well do I expect this treatment to work? What are the potential side effects of the treatment, and what are the patient’s goals? And when you sort of lay all those different pieces out, you then usually come up with something that becomes pretty clear what the best thing to do is.  

So, I’ll give you just a very concrete example of this. Sometimes, we have treatments where the medical data would suggest that they might work as well as one another, right? There’s no clear difference between each of the two treatments. But maybe one of the two treatments requires you to be in the hospital, and one of the treatments allows you to be at home.  

So, that’s an important discussion to have with the patient because some patients, believe it or not, want to be in the hospital, because they’re worried about being at home and having to manage this all themselves. Some patients don’t want to be in the hospital. Some patients want to be at home, because they’re scared of the hospital, or they’re worried the food’s going to be terrible.  

And then, that would be important in helping the patient make the decision for their treatment.  

Katherine Banwell:

Right. You mentioned earlier, Dr. Stein, the difference in ages and how you would treat different people depending on their age. So, when you’re choosing a treatment, you obviously look at age. What else? Things like comorbidities?  

Dr. Stein:

Yeah, so age, so I’m not ageist. So, it’s more that as people get older – and this is just a fact of life – as everyone gets older, their organs don’t work quite as well anymore, right? Things start breaking down as you get older. So, certain treatments aren’t appropriate for older people because the treatments a younger person, because their organs are working at 100 percent, may be able to handle it, while an older person, where their organs might only be working at 60, 70 percent, the treatment might not be as good of a choice for them. 

So, that’s what I mean. So, as people age, their comorbidities increase. So, we always look at comorbidities, and if you had an 80-year-old that was running marathons, I might think about their treatment differently than an 80-year-old who is not running marathons. But most 80- and 85-year-olds aren’t running marathons, so that’s why we sometimes think about their treatment differently.  

Katherine Banwell:

Yeah. Why is identification of genetic markers essential before choosing treatment?   

Dr. Stein:

Because when you know the genetic markers, you can target the genetic abnormalities, sometimes with specific targeted therapies, with therapies that fit like a key in a specific lock. And those targeted therapies have been shown, in some cases, to improve the survival of the patients, without much cost, without much toxicity. So, I’ll give you an example of this.  

There is a very common genetic abnormality in patients with acute myeloid leukemia called the FLT3 or FLT3 mutation. When you have that mutation, there is a targeted therapy that targets the FLT3 mutation called midostaurin, and it’s been shown in a very large clinical trial that the addition of the targeted FLT3 inhibitor midostaurin in combination with chemotherapy leads to better overall survival than chemotherapy alone.   

So, you need to know that information because you want to give your patient the best chance at beating the disease. And that’s why it’s also important to try to get this information back quickly. You know, no one wants to be sitting around waiting for four weeks to find out if they’ve got a specific mutation. And we’ve gotten better. I think medical centers generally have gotten better at getting this mutational information back to their doctors relatively quickly. 

 Katherine Banwell:

Does every patient get this standard testing? 

Dr. Stein:

It is – does everyone get it? I don’t know. But “Should everyone get it?” is, I think, the important question. Yes, everyone should get this testing.  

 It is incorporated into the NCCN and National Comprehensive Cancer Network and European Leukemia Net guidelines. It is important not only because you can think about targeted therapies, but it is also important for prognostic reasons, meaning that certain mutations lead to a higher risk of relapse, and those mutations in a patient might lead me to recommend a stem cell transplant, which is sort of the most intensive thing we can do to help prevent a relapse, while other mutations, which might be “favorable”, in quotes, they might lead me not to recommend a stem cell transplant.   

So, I think this mutational testing is the standard of care and should be done in every patient with newly diagnosed acute myeloid leukemia.  

Katherine Banwell:

Once treatment has begun, Dr. Stein, how do you know if it’s working? 

Dr. Stein:

So, that’s a good question. So, the good thing about acute myeloid leukemia when it comes to understanding what’s going on, you know, it’s a disease of the bone marrow cells. And we do bone marrow biopsies to see how things are doing. But no one likes a bone marrow biopsy. It can be a somewhat uncomfortable procedure.  

Katherine Banwell:

How often would a patient need to have a biopsy?  

Dr. Stein:

Yeah, so they have bone marrow biopsies at diagnosis, and then they often will have bone marrow biopsies two weeks to a month later.  

And then, if they’re in remission, basically any time you think if you want to check to see if they’re in remission or if you suspect the patient is relapsing. Then, you would do a bone marrow biopsy. But what I was getting at is that but you have blood. And the blood is kind of like the bellwether of what’s going on in the bone marrow.  

So, the analogy I use for my patients is, you know, when you’re driving your car and you have – you know, you don’t open the hood every day to make sure the car is running okay. You know, you’re driving your car, and if your car starts making a funny clinking sound, that’s when you open the hood.   

So, the blood is like the clinking sound. If you see something going wrong in the blood, that’s when you know you’ve gotta open the hood and look under the hood. If the car is running just fine and you don’t see anything wrong in the blood, using the analogy, maybe you don’t need to do a bone marrow biopsy. 

Katherine Banwell:

What if a treatment isn’t working? What if it stops working or if the patient relapses? What do you do then?  

Dr. Stein:

Yeah, so when a patient relapses, which unfortunately happens more than we want it to, it’s important No. 1 to do another bone marrow biopsy and at that point, do that mutational testing again because the mutations that are present at the time of diagnosis are not necessarily going to be present at the time of relapse, and sometimes, a new mutation might occur at the time of relapse. And again, what that mutational profile shows can help determine what the next best treatment for the patient is. There might be standard-of-care therapies. More chemotherapy might be recommended.  

When a patient relapses, I usually – excuse me – try to get them on a clinical trial because that’s the point where I think clinical trial drugs really have potentially major benefit for the patients, to help get them back into remission. 

Katherine Banwell:

Why is it essential for patients to share any issues they may be having with their healthcare team, specifically, sharing their symptoms and side effects?  

Dr. Stein:

Well, it’s important because we want to help you. I mean, I think that’s what it comes down to. All of us, whether it’s your doctor or your nurses or your nurse practitioner or physician’s assistant or anyone who is part of the healthcare system, we went into this business to help people. I mean, we knew what we were getting into when we went into this, and we want to help people. And one of the ways you help people is you help with their symptoms. So, if you’re not feeling well, you call up, and you say, “I’m not feeling well,” we can help you with that. You shouldn’t suffer in silence.  

I sometimes have patients who will say to me, “Oh, I was going to call you, but I didn’t want to bother you.” You’re not bothering us. This is what – it’s not like you’re calling and asking for mortgage advice, right? This is what we do. So, it’s very important to call us because the other thing is that you’re going to be more – it’s more likely that you’ll be able to complete your treatment if we manage the side effects that you’re having rather than just ignoring them.  

Katherine Banwell:

Yeah, that’s great advice. With more oral therapies becoming available, patients now have a role in self-administering their treatment. So, what happens if a patient forgets to take a medication? Does that impact its effectiveness? 

Dr. Stein:

The easy answer to that question is probably not. You know, if you forget to take a medication for three weeks, that’s not a good thing, but if there’s a – you know, this happens all the time, right?   

You’re busy, and you just forget. If you forget to take a medication one night or one day, it almost certainly is not going to make a huge difference. Having said that, you shouldn’t see that as license to not be careful. So, it is important to try. So, set an alarm; put out a pill container do the kinds of things that can help you.   

The other thing, there is a certain what I would call pill fatigue that sets in. Often, patients with AML are taking multiple medications at multiple times a day, and it can be hard. And at my center, we have pharmacists who do a lot of different things, but one of the things they can help with is sort of streamlining patients’ pill burden to make it easier for them to remember and to take the medications when they’re supposed to take them.  

Katherine Banwell:

When a patient does forget to take a dose or even a couple of days’ doses, should they call their healthcare team and let them know? 

Dr. Stein:

Yes, always call. Always call.  

Katherine Banwell:

Okay. I want to make sure we get to some of the audience questions. These were sent to us in advance of the program. Let’s start with this one from Patrick. He writes, “Are there any clinical trials looking at maintenance therapy for the AML patients, especially older patients?” 

Dr. Stein:

Yes, there are a number of clinical trials that are looking at maintenance therapy for older patients with acute myeloid leukemia. Some of those trials are maintenance therapies with targeted agents that are against specific mutations. Some of those trials are clinical trials with more broadly active agents that might be able to be used as maintenance therapy, so yes. Maintenance therapy is something that is really coming to the fore, and I would encourage you to seek out trials that might offer maintenance therapy.

Katherine Banwell:

Aaron sent in this question: “What are the most promising new effective drugs on the verge of being approved by the FDA, and what do they do?” 

Dr. Stein:

Yeah, so I’ll just mention the one I mentioned a second ago, and that’s the class of drugs called menin inhibitors. I wouldn’t quite say they’re on the verge of being approved by the FDA, but I think that they’re very, very powerful drugs that within the next two or three years, they will likely be approved by the FDA if the early clinical trials continue to pan out. And those are drugs that at least in the early experience, seem to be specific for patients with these NPM1 mutations or these MLL rearrangements. And your doctor will know what those are if you ask them, “Do I have an NPM1 mutation, or do I have an MLL rearrangement?” 

Katherine Banwell:

Thank you for that, Dr. Stein. And to our viewers, please continue to send in your questions to question@powerfulpatients.org, and we’ll work to get them answered on future programs.   

What advice do you have for patients to help them feel confident in speaking up and becoming a partner in their own care? 

Dr. Stein:

My advice is, speak up. You just speak up. It’s very important. It’s your – you know, at the end of the day, this is a disease that you are experiencing. Your doctor is there to partner with you and to guide you, but it’s your body. It’s your disease, and you need to be very vocal in what you’re experiencing and advocate for yourself.  

Katherine Banwell:

If a patient has difficulty voicing their questions or concerns, are there members of the support staff who could help?  

Dr. Stein:

Most centers have a social worker on staff that can help them out. I highly, highly encourage all of my patients to meet with a therapist or a psychologist that specializes in taking care of patients with cancer. I have become more vocal about this that I see. Really, it’s probably the best thing a patient can do for themselves, and there’s no downside. If you don’t like it, you don’t have to go back. Do one appointment and not go back. But that can be extremely helpful, extremely helpful.  

So, it’s important in both ways. You need to alert your doctor that you might be feeling one way, but I think it’s also on the doctor to sort of take visual cues from the patient when they see them to understand what they might need and to make those kind of recommendations.  

Katherine Banwell:

Yeah. As we close out our conversation, Dr. Stein, I wanted to get your take on the future of AML. What makes you hopeful?  

Dr. Stein:

Oh, so many things make me hopeful. I mean, we understand this disease so much more than we understood it even 10 years ago. There are all sorts of new treatments that are being developed. We’re improving the survival of our patients with the new treatments that have already been approved over the past 10 years. And I really think the golden age of AML treatment is upon us, and I really think that – and some people might think I’m crazy – but I really think that by the time I’m done with this, you know, one day, I’ll get too old, and I’ll decide I need to go retire and spend time with my family. But I think by that time, we’re going to be curing the vast majority of our patients. 

Katherine Banwell:

That’s so positive. It’s great to hear that there’s been so much advancement and that there’s so much hope out there for AML patients. I want to thank you so much for taking the time to join us today, Dr. Stein.  

Dr. Stein:

Okay, thank you. It was really nice to be here.   

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 joining us today.  

How Can Specific Biomarkers Impact Lung Cancer Progression?

How Can Specific Biomarkers Impact Lung Cancer Progression? from Patient Empowerment Network on Vimeo.

Lung cancer progression can be aided by monitoring of biomarkers, but what do they indicate? Expert Dr. Christian Rolfo from Mount Sinai explains biomarker characteristics that help monitor disease progression and how clinical trials help in treatment advances.

See More from Best Lung Cancer Care

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What Are the Latest Lung Cancer Treatment Updates?


Transcript:

Dr. Nicole Rochester:

So with regard to the biomarkers, you mentioned that these are kind of unevenly distributed among different populations depending on your origin, and so how does that play into the progression of the disease, what do we know about why patients with specific biomarkers have a different degree of disease progression?

Dr. Christian Rolfo:

Yeah, so we know more or less that the characteristics, I mean more or less in terms of the evolution of the clinical characteristics of these patients, in terms of organ affection in case of progression, but what is most important of this is that we are able to continue to identify, and I say monitoring these patients with liquid biopsy, for example, this is a good tool to understand or to understand it a bit better, which kind of mechanistic involvement. 

So because we have, for example, patients who were receiving the case that I was discussing before EGFR mutations and they received one graft from the very beginning, a third-generation TKI is the one that is approved for the first line, and this patient has a progression. The possibility to have a mechanism of resistance is different, so we can have mutations that are coming in the same pathway, so in the same area, same kind of mutation, but different location, just to the people understand is the kind of line and we have the mutation that is here, the one that we are attacking, but we have another mutation that is in this area, and it’s not covered by the track that is covering this mutation. 

So we have nowadays drugs that are going to, in this area in clinical trials, or we have in other cases other areas of the task of mutations that have nothing to do with the original one. So we are activating another kind of pathway, or we are transforming the tumor from one kind of tumor to another kind of tumor, so for this reason, identify which kind of mechanism of resistance is in place can have an important or have important implications for how we are treating these patients,  so we need to look at that to treat the patients.

Dr. Nicole Rochester: Wonderful. And speaking of resistance, we know that there are some patients who end up trying multiple therapies in order to treat their lung cancer, are there alternative treatment strategies for lung cancer patients who have failed all therapies? 

Dr. Christian Rolfo: 

Yeah, absolutely, we have research in lung cancer is never stopping in oncology generally, but in lung cancer it’s really exciting to see how this research is evolving, and it’s arriving to the patients the meaning of the research when we are doing access to the patients, to the discovery of the finding that we have, and obviously, we have strategies in the clinical practice, but also we have the clinical trials. So clinical trials, and that is something we need to try to define very well because some patients believe that when we are going to clinical trials there are no more options or we don’t have any other options to do. 

We are sometimes using clinical trials even in the first line, so even in patients that are for the first time being treated. Because we know that some of the cases we are treating patients with from some standard of care and using drugs on top, we want to explore it, we can improve these outcomes that we already know. That could be also a clinical trial, that is also a clinical trial. So don’t take the participation in a clinical trial as the last option that you have, sometimes you will go to your doctor and the first time that you see a doctor for your first diagnosis, they can propose a clinical trial. 

And this is really valuable. What we really appreciate is the collaboration of the patients to be in clinical trials, because we need to remember that the drugs that we are using today were analyzing other patients before, so the treatment that you are receiving in a standard of care today were before a clinical trial, it’s really important how we can interact with the research and the clinical practice very easily, so we have also some options that are…for what we call early drug development, that there are some drugs that are in patients who are receiving the standard of care, and they have the opportunity to be treated in new drugs, and you can discuss…believe me there, and 

I know that there is a lot of questions about clinical trials but the clinical trial setting is really restrictive, it’s very well-coordinated, so you would be part of a very coordinated and structured things that they try to protect the patients in the first instance, and try to understand also how we can help the patients and the future generations. So that is really why we appreciate patients that the contribution of patients that are giving to this clinical research because it’s helping to advance the knowledge for the new patients as well.

Dr. Nicole Rochester: 

And I really appreciate how you described clinical trials, and particularly your distinction about it’s not always this last ditch effort that sometimes you all are using clinical trials as first-line therapy. One of the common things is that clinical trials are tomorrow’s medicine today, and helping patients and families to understand that there’s value in being involved in clinical trials and that…and I think with COVID there’s a little more understanding, but certainly, we have a long way to go, and so I appreciate you sharing that. Do you have any specific examples of patients in your practice, and not names, of course, but examples of…that have benefited from clinical trials?

Dr. Christian Rolfo: 

Absolutely, we have several of examples, and actually FDA was doing a terrific job in the last year to try to get access quickly access to the drugs for patients, and some of this access that was granted was based in clinical trials that we’re starting for a Phase I or Phase II trials, owe are really doing a very rapid evolution of the drug development, and this is a revolution actually of the drug development because we have access very quickly. I can tell you that it was certainly in my career, several patients in clinical trials that they got benefits. Obviously, clinical trials are answering questions, so that is the way that we can answer questions scientifically and is the only way that we can advance in clinical therapeutics. 

How Can Biomarkers Help With Lung Cancer Treatment?

How Can Biomarkers Help With Lung Cancer Treatment? from Patient Empowerment Network on Vimeo.

Biomarkers can assist with lung cancer treatment, but how are they used exactly? Expert Dr. Christian Rolfo from Mount Sinai explains what is examined in biomarkers and how they aid treatment of specific population groups.

See More from Best Lung Cancer Care

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How Can Specific Biomarkers Impact Lung Cancer Progression?

What Are the Latest Lung Cancer Treatment Updates?


Transcript:

Dr. Nicole Rochester: 

We know that no two lung cancers are the same. Can you explain to the audience how biomarkers help with lung cancer treatment and they can be so important? 

Dr. Christian Rolfo: 

Yeah, we have different…as I say, we are looking at specific characteristics from the tumor when I’m referring to genomic alterations that I’m not referring to something that you can get from your family and bring to your descendants. So I’m talking about mutations that are occurring inside the tumors and only for the tumor, and so affecting only the subject that has this patient that has this alteration. So these biomarkers are an important way to identify populations that we can treat specifically, and I would like to be a little bit more specific on that. We have some of the alterations, for example, one of the mutations that we call EGFR or epidermal growth factor receptor mutation that is supported in different populations in different frequencies. For example, if we have patients that are with an Asiatic origin, we have there the possibility to have a…and I’m referring, for example, Chinese, Japanese, this area of the East Asia, we have a hyper-prevalence of these mutations in around 50 percent of the patients with lung cancer, non-squamous we’d say this is another characteristic of the tumor can have this specific alteration. If we are moving, for example to Latinos, the pains of the areas of Latinos they are coming from, if you have Mexican or, for example, Peruvian, they have also due to their ancestry, they are similar to the Asiatic population, 40 percent we’re going to white populations and Anglo-Saxons or Europeans, they have around 7 to 15 percent  according to the different regions. 

African Americans within 15 to 20 percent. So these kinds of alterations are giving us the opportunity to treat and we have nowadays inhibitors and that’s drugs that are from first, second and third generation, so we were evolving in January, this pharmaceutical in January to develop all drugs that are able to penetrate in the brain and acting not only in the tumor, but also in brain metastases. And patients who have this mutation, for example, are treated in first line, in front line, or the first treatment that they receive are pills, no chemotherapy. So for this reason, and that is something that is important because when we know that patients, when they start this journey of lung cancer diagnosis before they see an oncologist, they were struggling to get the diagnosis and then we’re passing through several doctors from the general practitioner or to the emergency room, going to CT scan and then a biopsy then a pulmonologist until they get the diagnosis, it’s a big period of time sometimes that we are very nervous because we want to each patient to have a treatment as soon as possible, and sometimes when they arrive to us, we say they need to wait until we have the results of these biomarkers. 

So it’s difficult to understand, I put in the place of the patients and the families are really difficult to understand that I was passing a lot, I went here, I came here and I want your treatment right away, but this period that we are asking to wait is really important, because we will have information that can change radically the treatment and the history of these patients. So one of the problems that we have in America is the lack of testing, so we have all the tools to test the patients, but if we are looking at some of the statistics, 50 percent of the patients have been tested. 39 percent if we are moving to groups, for example, of AfricanAmericans, so we need to be very careful that don’t push to get the treatment very quickly without having all the elements to this thing, which kind of treatment is the most adequate for the patient. 

Dr. Nicole Rochester:

That is such important information, and I really appreciate that, I appreciate it. That you put it in the perspective of the patients and family members. And that grueling, long wait, long time to diagnose this, and finally you’re in front of a specialist and the perception is that, Okay, now I’m going to get this treatment that I need, and then like you said to hear, now you have to wait a little bit longer, but also to understand that that wait is important to make sure that you get the treatment that is meant for your specific type of cancer, I think that is so incredibly important.

Dr. Christian Rolfo:

And believe me, we are trying to push as well from the that there are, unfortunately, technical times that we cannot overcome that are for testing and for having these results, and we can do that by like I said liquid biopsy, but also tissue biopsy, so we are sending the tissue that the patients gave for a biopsy in a biopsy or in a resection when they have surgery. We take these small biopsies and we send them for analysis and take longer sometimes, so it’s a pity and we know, but it’s the only way to go for the right treatment. 

How Do Test Results Impact Myeloma Treatment Options?

How Do Test Results Impact Myeloma Treatment Options?  from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Melissa Alsina reviews the test results that are taken into consideration when choosing a treatment approach for patients.

Dr. Melissa Alsina is an associate professor of medicine in the Blood and Marrow Transplant Program at Moffitt Cancer Center in Tampa, Florida where she also serves as head of the Multiple Myeloma Transplant Program. Learn more about Dr. Alsina, here.

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Key Factors That Guide Myeloma Treatment Decisions


Transcript:

Katherine:

We know that patients undergo testing when diagnosed. How do test results affect treatment choices? 

Dr. Alsina:

So, in general, we do a bone marrow, we check for the genetics of the myeloma cells, see what are the genes that are affected in the myeloma cells, and that helps us define myeloma as high-risk or standard-risk, and that can help us decide what treatment we want to give these patients. Unfortunately, it’s not totally well defined. 

I wish we could use that in a better way and there are drugs that could really target, but there is some information. We know, for example, that proteasome inhibitors are important for patients with high-risk myeloma, so we definitely try to include that in a patient that is high-risk, and the other thing is that patients that are high-risk, it’s even more important to get to that remission, so we’re going to push treatment to get there, treat these patients a little bit more aggressively. 

Other than that, depending on, for example, what are the blood counts – some patients have a lot of bone marrow involvement and their blood counts are very low. This is not common, but it happens, and so, when that happens, we might be more aggressive up front and give these patients more aggressive chemotherapy to clean the bone marrow before changing them to the more normal therapies because the treatments that we give, like Revlimid (lenalidomide), Velcade (bortezomib), Darzalex (daratumumab) can depress the counts, right? 

So we’re in that battle. The patients already have low counts, we give the treatment, the treatment lowers the counts further, so it’s hard to give these treatments in these settings. And then, the third thing that we take into account is kidneys. About 25 percent of the patients will have renal insufficiency when they are diagnosed. Some of these drugs, particularly the immunomodulatory drugs like the Revlimid are metabolizing the kidneys, so it’s very hard to dose these drugs when the patients have renal insufficiency. 

So sometimes, for these patients, we avoid the IMiDs up front. We give a different combination until the disease gets better, and then we introduce the IMiDs. We think these immunomodulatory drugs like Revlimid are super important in the treatment of myeloma, so we want to give them, but sometimes we have to delay starting them until the patient’s kidney function improves.  

Current Treatment Approaches for Bladder Cancer

Current Treatment Approaches for Bladder Cancer from Patient Empowerment Network on Vimeo.

Dr. Shilpa Gupta provides an overview of available bladder cancer treatment approaches and discusses the factors that impact therapy decisions.

Dr. Shilpa Gupta is the Director of the Genitourinary Medical Oncology at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. Dr. Gupta’s research interests are novel drug development and understanding biomarkers of response and resistance to therapies in bladder cancer. Learn more about Dr. Gupta, here.

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Transcript:

Katherine:                  

You’ve touched upon treatment options but let’s walk through the treatment approaches for bladder cancer and who they might be right for, and I’d like to start with surgery. Who would be a good candidate for surgery?

Dr. Gupta:                  

I think patients who are otherwise fit, that is, they have good performance status, don’t have a lot of cardiac or other comorbidities, are not very obese, and of course have to be fit for any major procedure are usually considered good surgical candidates. But, as far as – In terms of staging, the patients with stage I, if BCG does not work in them or immunotherapy doesn’t work, they are recommended surgery if they are good candidates.

If they are not good candidates, we then – our role as medical oncologists is to offer other systemic therapies. As far as stage II cancer is concerned, the gold standard has been chemotherapy, followed by surgery but that’s the gold standard.

It may not apply for every patient. Depending on how fit patients are. Are they – we don’t usually just go by their chronological age but how fit they are? What are their comorbidities? If surgery is going to be a big burden for them moving forward, then we do talk about radiation and chemotherapy and other bladder preservation approaches.

Katherine:                  

What about immunotherapy and targeted therapies? Who would you use those on?

Dr. Gupta:                  

Well, since the advent of immunotherapies back in 2016 they’ve really – we’ve made a lot of progress and changed the way treat bladder cancer and the overall survival has improved by leaps and bounds with all these drugs.

Immunotherapy now plays a role in different stages. It is approved for superficial or non-muscle invasive bladder cancer if, let’s say, BCG doesn’t work. In muscle invasive disease we have along with others shown that immunotherapy is safe and effective, although it is not yet FDA approved, so there is a lot of clinical trials going on to prove its superiority in combination and by itself.                                   

And, in metastatic disease or locally advanced disease immunotherapy plays a huge role for patients who have either disease recurrence after chemotherapy or are not good candidates for any chemotherapy.

I would say that immunotherapy is a very big – plays a very big role in the treatment. Unfortunately, not everybody responds to immunotherapy only about 20 to 25 percent of patients do.

 That’s why we have these other novel therapies that have been coming through, like antibody drug conjugates, namely enfortumab vedotin, sacituzumab govitecan, and targeted therapy in the form of an FGFR inhibitor was the first targeted therapy that was approved a couple of years ago for patients who have a mutation in their tumors.

That’s really personalized medicine for those patients.

Katherine:                  

Right. What about biomarker testing? Does the presence of certain biomarkers impact certain treatment options?

Dr. Gupta:                  

That’s a great question and we’re all striving to find the perfect biomarker in bladder cancer. In the past we thought that expression of PD-L1 in the tumor cells and immune cells is a marker of how well the immunotherapy will work, but we have learned over the past couple of years that biomarker has turned out to be quite useless.

We don’t really need that to guide our treatment. We’re still depending on clinical biomarkers for immunotherapy use or chemotherapy use. I would say that the biomarker question is still being looked at and eventually I would say it’s not going to be one biomarker, but a composite of several different biomarkers that we will be able to use comprehensively.

What Do Metastatic Breast Cancer Patients Need to Know About Genetic Testing?

What Do Metastatic Breast Cancer Patients Need to Know About Genetic Testing? from Patient Empowerment Network on Vimeo.

What do metastatic breast cancer patients need to learn about genetic testing? Expert Dr. Sarah Sammons explains the difference between germline testing versus somatic testing and defines key terms, including biomarker testing and genetic mutations.

Dr. Sarah Sammons is an oncologist at Duke Cancer Institute and Assistant Professor of Medicine at Duke University School of Medicine. Learn more about Dr. Sammons here.

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Transcript:

Katherine:

Many patients are confused by genetic testing. Let’s look at the difference between germline and somatic testing.

Dr. Sammons:

Yes, that’s a really good question and one that comes up in the clinic quite frequently. When I tell a patient that I want to get some sort of genetic testing, they often are confused, and say, “Well, I’ve already had genetic testing, maybe when I was first diagnosed with early-stage breast cancer.” And so then, I do often times need to explain what the difference between germline and somatic genetic testing is.

So, germline testing is testing that’s done on cells in your body that actually don’t have cancer. And the purpose of germline testing, which we often do in early-state breast cancer or in metastatic breast cancer, is to understand if you have inherited genes that could pre-dispose you to developing breast cancer. But also, in the metastatic setting, it’s important to do germline testing because we do have drugs that are approved for patients that have germline mutations in the BRCA genes. And research is evolving, but there are other germline genes of interest that could be biomarkers for other therapies.

Somatic testing is basically genetic testing on the breast cancer cells themselves. So, most often we will get a biopsy, usually of a metastatic area, like the liver, or bone, or lung. Really the safest, most accessible place. If we’re able to safely get a biopsy, oftentimes we’ll send somatic testing – that’s also referred to as usually next generation sequencing – is all somatic testing. And that tests mutations that have developed in the breast cancer itself. It could potentially be biomarkers for optimizing and tailoring personalized treatment approaches to the patient’s cancer.

Katherine:

I’d like to define a few terms. First of all, what is biomarker testing?

Dr. Sammons:

That’s a really good question. So, a biomarker is really anything – it could be a gene; it could be a protein – that is expressed on a patient’s cancer, that makes them a good candidate for a certain drug, essentially.

So, one of the earliest biomarkers that we’ve had in breast cancer – and still, I would argue, the most important biomarkers – are estrogen receptor and HER2.

Now, we test all breast cancers for estrogen receptor and HER2 because we know for estrogen receptor – if a patient has estrogen receptor high positivity at their initial diagnosis, that is the best biomarker for endocrine therapies, whereas HER2 present on a breast cancer cell – patients that overexpress HER2, they are great candidates for drugs that specifically target HER2.

So, it simply means that we found something on their breast cancer cell that makes them a good candidate for a treatment.

Katherine:

What is a genetic mutation?

Dr. Sammons:

So, genetic mutations are a permanent change in the DNA of a gene, in either a cancer cell or a cell that somebody was born with. So, it’s a change in the DNA sequence. And some gene mutations drive cancers to grow. Some mutations do not drive cancers to grow. Generally, in the treatment of all advanced cancers, we only target with drugs those gene mutations that we know are what we call “driver mutations.” So, mutations that actually cause the cancer to grow.

What Are Biomarkers and How Do They Impact Lung Cancer Treatment Options?

What Are Biomarkers and How Do They Impact Lung Cancer Treatment Options? from Patient Empowerment Network on Vimeo.

What are lung cancer biomarkers, and how do they impact treatment options? Dr. Isabel Preeshagul defines biomarkers and explains how different biomarkers may help determine treatment options and aid in predicting treatment response. 

Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul here.

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Transcript:

Katherine Banwell:

Well, let’s define a few terms that are often confusing for patients. What are biomarkers?

Dr. Preeshagul:

Those are somatic alterations in the tumor just like EGFR, or ALK fusions, or MET exon 14, or MET amplification, or KRAS G12C.

These are all genes that are altered in the tumor. And these are genes that drive the tumor to grow. There are also other markers like PD-L1, which is a marker for response to immunotherapy. And there are various markers.

I could go on and talk about it for hours, but those are the more common ones that we know how to treat and how to handle and prognosticate.

Katherine Banwell:

And another term that’s sometimes confusing, what is a genetic mutation?

Dr. Preeshagul:

So, for genetic mutations, you have germline, and you have somatic. So, a germline mutation may be something like a BRCA1 or a BRCA2 that we see in patients with breast cancer or prostate cancer versus a somatic mutation which would be EGFR that I had mentioned or ALK fusion. So, germline mutations are the ones that we worry about being heritable.

And somatic mutations are those that are not thought to be heritable but thought to happen spontaneously within the tumor itself and cause the tumor to grow. We are constantly learning more about these though, however. But it’s really important to talk with your doctor to see if you have a germline mutation or a somatic mutation or if you have both.

And it is never wrong to seek an opinion with a genetic counselor to make sure that everyone in your family is safe, that you’re up to date on age-appropriate cancer screening, and that your family gets screened appropriately as well if indicated.

Katherine Banwell:

Are there specific biomarkers that affect lung cancer treatment choices?

Dr. Preeshagul:

Oh, definitely. One that I had mentioned is PD-L1. And this is a marker that we look for expression. So, based on FDA approval for pembrolizumab, if you have an expression of 50 percent or more, you are able to get immunotherapy alone in the upfront setting. If you have less than 50 percent, we often give you chemotherapy plus immunotherapy. And that’s based on a clinical trial known as KEYNOTE-189.

Other markers such as EGFR, as I had mentioned, ALK fusions, RET, NTRK, MET exon 14, ROS1, KRAS, HER2, you name it, those are alterations that we look for ideally in the upfront setting as well and can really affect treatment planning.

And those patients that harbor mutations like EGFR and ALK and ROS1 or MET exon 14, we know that these patients do better with targeted therapy upfront, not standard-of-care chemo. So, it’s really important to know about the presence of these alterations before you start treatment if possible.

What Is a CLL Biomarker?

What Is a CLL Biomarker? from Patient Empowerment Network on Vimeo.

What is a chronic lymphocytic leukemia (CLL) biomarker? Dr. Paul Barr provides the definition of a biomarker and explains how they may assist in determining a CLL patient’s prognosis and treatment approach.

Dr. Paul Barr is Professor of Hematology/Oncology at University of Rochester Medical Center. Learn more about Dr. Barr, here.

See More from Engage CLL


Related Resources:

 

An Expert’s Perspective on CLL Research Advances

Transcript:

Katherine:

Often patients are confused with the term biomarker or biomarker testing. Would you define that for us?

Dr. Barr:

Sure. Biomarkers, I think of them as surrogates to understand the bigger picture. A lot of times what we really want to know when we’re meeting a patient is what’s going to happen in the future? What’s going to happen in five and 10 years from now? Or maybe we want to know as we’re getting closer to treatment, how well is this going to work and how long is it going to work for?

So, we do a lot of research in developing surrogate tests to try to give us an idea of what the future might hold. And so, we have developed a number of molecular genetic tests that we test for, and they give us an estimate of what to expect in terms of the patient’s prognosis.

Or perhaps they help predict for which treatment might work best. So, we often, will look at some molecular aberrations or some genetic tests that tell us about abnormalities just within the CLL cells in the leukemia cell. And they can predict for more slowly or rapidly growing disease. And other tests, might predict for, which drug might serve a patient best in terms of efficacy or how long would it work or for safety.

So, think of that as useful tools to help us give the patients an idea of what to expect over time.

MPN Treatment: What Is the Role of Biomarkers?

MPN Treatment: What Is the Role of Biomarkers? from Patient Empowerment Network on Vimeo.

What role do biomarkers take in myeloproliferative neoplasm (MPN) treatment? Dr. Naveen Pemmaraju defines biomarkers and explains how molecular mutations play into MPN disease risk levels and treatment options.

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Pemmaraju, here.

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What Are the Considerations When Choosing Myelofibrosis Therapy?

What Are the Considerations When Choosing Myelofibrosis Therapy?


Transcript

Katherine Banwell:

Dr. Pemmaraju, let’s talk about biomarker testing. Can you help us understand what biomarkers are and how they may affect treatments?

Dr. Pemmaraju:     

Yes. Biomarkers – I think that word gets mentioned a lot with really no definition, because it’s one of those words that can be whatever someone wants it to be. So, you’re right. For us, it’s a very important word in MPN. Bio meaning of life, scientific, and then marker meaning some kind of a measuring stick that has a value.

Well, there are two ways to look at biomarkers. One is the obvious, which is we have the defined big three molecular mutations. So, that’s JAK2V617F, followed by CALR mutation, followed by MPL.

Those are the big three. Those make up about 90 percent of all patients with MPNs. You’re technically not born with them, although new data suggests that you may acquire these mutations right after birth. So, those markers are important because they can be used to diagnose the disease, right? Particularly in the challenging patient. They have high platelets, you can’t tell if it’s reactive or ET. Okay, so they’re helpful with diagnosis.

Maybe some studies have shown that some of these markers can be predictive, Katherine, of blood clots. Let that research be ongoing. And then, obviously, some of these may be helpful in terms of designing the future treatments, particularly targeted therapies. So, I think biomarkers are part of our field, if you look at it that way, at diagnosis and risk stratification prognosis. But there are other factors that are starting to come out. One is there are molecular mutations outside of these big three.

So, outside of JAK2, CALR, and MPL, that are very important actually. Not everyone is checking for them. They are ASXL1 mutations, EZH2, IDH1 and 2, so on and so forth.

So, these are extended molecular markers that can be checked at some doctors’ offices that now, in the latest scoring systems, if you have one of those or more than one or two, they can elevate your risk score. So, if you have low risk or intermediate risk myelofibrosis, they may make you intermediate or high risk.

So, that may be a bit more complicated than what most people are aware of. But just so you know, there are markers that can be readily checked that can tell if your disease may be a bit higher risk than we though, say, 10 years ago.

I think other biomarkers that we look at are some of the labs that are just the regular labs that are on almost every panel, but they can tell a lot about the disease. There’s the LDH, lactate dehydrogenase. There are several markers, such as CRP and sed rate.

So, anyway, there are a lot of labs that we can check depending on where you are in your disease state that can kind of tell us a lot about how inflamed you are, how active your disease is at the moment, and then that will lead to further confirmatory tests. So, I think, yeah, in general, this is an active, developing area of research in our MPN field.

Identifying Biomarkers Gives Doctors Known Targets to Treat Many Cancers

This blog was originally published by Cancer Treatments Centers of America on August 21, 2019, here.

Biomarkers
Doctors are increasingly relying on biomarkers, which help determine a patient’s overall health and/or the presence of disease. Learn what biomarkers are and why they are increasingly important in cancer care.

When faced with opposition, it’s beneficial to learn as much as possible about the opponent. A pitcher reads a scouting report before facing a lineup. An army consults intelligence before engaging the enemy in battle.

The same principles apply to the treatment of some cancers. When treating a tumor, it’s important for a doctor to know as much as possible about that cancer—specifically, what is driving the tumor’s growth.

To get the inside information on a tumor, doctors are increasingly relying on biomarkers, short for biological markers, measurable signs or substances in the body that may indicate a patient’s overall health and/or the presence or progression of disease.

The discovery of biomarkers in cancer drastically changed the course of cancer treatment. For decades, many cancers were treated similarly, with surgery, radiation therapy or chemotherapy. Identifying biomarkers in cancer cells has led to the development of new precision medicine drugs, such as targeted therapy and immunotherapy, designed to target specific features in cancer cells, potentially reducing the damage to healthy cells. “The routine use of a variety of biomarkers has substantially changed the way in which cancer medicine is practiced,” says Maurie Markman, MD, President of Medicine & Science at Cancer Treatment Centers of America® (CTCA), “from providing more accurate prognostic information to assisting in the prediction of specific therapeutic strategies that are more likely to result in a favorable outcome for an individual patient.”

What are biomarkers?

A biomarker is any measurable indicator of a person’s health. Blood pressure is a biomarker, as are body temperature, blood sugar and cholesterol measurements. In cancer, biomarkers also include proteins, hormones, gene aberrations, such as mutations or rearranged genes, and other molecules found in or on cancer cells. Cancer biomarkers may be found in routine blood, urine or stool tests. Others may require a biopsy and/or advanced genomic testing to uncover. “Genomics has made it so much easier to find gene mutations,” says Arturo Loaiza-Bonilla, MD, MSEd, FACP, Vice Chair for the CTCA® Department of Medical Oncology. “Now we may be able to target a mutation and potentially get the cancer to stop growing.”

Biomarkers play multiple roles in the treatment of diseases, such as cancer, including:

Diagnostic: Helping confirm the presence of disease, sometimes before symptoms develop

Prognostic: Helping forecast the progression and aggressiveness of the disease and the risk of recurrence

Predictive: Helping doctors identify how patients may respond to certain drugs

Biomarkers may play any or all these roles and more. Some biomarkers may be used to assess a patient’s risk of developing disease, the effectiveness of a treatment or whether a treatment is safe or toxic.

Common cancer biomarkers include:

  • BRCA1 and BRCA2 genes: Mutations in these genes may increase a woman’s risk of breast and ovarian cancer. In men, it may increase the risk of prostate cancer.
  • PSA: Prostate specific antigen may indicate prostate cancer. This biomarker may be used not just to diagnose the disease, but to measure its progression and how the treatment is performing.
  • HER2: Human epidermal growth factor receptor 2 is found in many cancers, especially breast cancer. The targeted therapy drug trastuzumab and other similar monoclonal antibodies may be a treatment option for patients with HER2-positive cancers.
  • BCR-ABL: This gene, known as the Philadelphia chromosome, is found in patients with chronic myelogenous leukemia. Presence of the gene may indicate the patient may respond well to treatment with a tyrosine kinase inhibitor drug such as imatinib.
  • PD-L1: Programmed death ligand 1 is the companion receptor to PD-1. It may indicate a cancer’s ability to evade the immune system. Immunotherapy drugs called checkpoint inhibitors may be an option to treat cancers high in PD-L1.
  • CA-125: High levels of cancer antigen-125 are found in many cancers as well as other diseases. Treatment options for cancers with CA-125 vary depending on where the cancer originated.
  • MSI-H: Microsatellite instability-high is a mutation in the DNA of cells found in many cancers, especially colorectal cancer. Checkpoint inhibitor drugs have been approved for cancers with MSI-H.

Difficult targets

Biomarkers don’t always tell the full story. Discovery of a biomarker that might indicate an increased cancer risk doesn’t mean a patient will get cancer. Not all cancers have identifiable biomarkers. And identifying a driving biomarker in a cancer does not necessarily lead to a treatment option. Some biomarkers for cancer have no corresponding targeted therapy or immunotherapy drug. For example:

  • TP53: Tumor protein 53 is a tumor suppressor gene designed to help stop cancer cells from growing. TP53 mutations are the most common found in cancer cells and may be found in most types of cancer.
  • RAS: About 30 percent of all cancers, including 95 percent of all pancreatic cancers, have known mutations in the RAS family of genes that control cell death and growth.

No targeted therapy drugs have been approved specifically to treat cancers with these mutations. “A number of recognized critical signaling pathways in cancer development, progression and resistance remain very difficult to ‘target’ to influence clinical outcomes,” Dr. Markman says. “The ability to successfully and safely target either or both of these pathways has the potential to be an important advancement in cancer management.”

Many cancers, especially solid tumors, have multiple biomarkers, any one of which may be able to drive a cancer’s growth. Target one biomarker, and another may take over as the driving mutation. And not all the same biomarkers are found in every cancer cell. “As cancer cells grow, they start to develop new abnormalities, mistakes made while the cells are multiplying,” Dr. Bonilla says. These new mutations may make the cancer more resistant to treatment.

Also, doctors need to take steps to prevent the patient from being harmed by the process of targeting a specific biomarker. For instance, patients on a checkpoint inhibitor that targets cancers high in PD-L1 may develop symptoms of autoimmune diseases, such as colitis. “The goal is to find the specific biomarker that every single cell expresses without compromising the normal cells,” Dr. Bonilla says, “because once you tell the immune system to kill a population of cells, it is going to kill all those cells, whether they are good or bad. But if you are able to find the specific biomarker that is the hallmark of this disease and needs to be eliminated, then it’s much easier to find a therapy.”

The discovery of biomarkers has led to game-changing developments in the cancer treatment. Women who learn they have BRCA mutations are now empowered to make potentially life-saving decisions to prevent breast and ovarian cancer. Men with slow-developing prostate cancer can now actively monitor their disease, in part, because their PSA levels can be measured. And research is ongoing to find new biomarkers to help in the treatment of other cancers and diseases, such as diabetes, Parkinson’s disease and heart disease.

“Biomarkers offer an opportunity to apply genomics to population health and see what diseases or conditions people may be predisposed to,” says Pamela Crilley, DO, Chair of the CTCA Department of Medical Oncology. “Am I going to get diabetes? Am I going to get elevated cholesterol? Is there anything I can do about it? Look at hereditary breast and ovarian cancers. The science has led to being able to prevent disease in patients with BRCA1 and BRCA2 mutations. Now we may be able to significantly reduce your risk of disease.”

A Conversation With Dr. Jo-Anne Vergilio

A new year means new programs! We’d like to introduce to A Conversation With, which is a collection of conversations with healthcare leaders, including patient advocates and various healthcare professionals, to take a closer look at the topics and issues important to empowered patients, care givers, and their families.

In our first segment of A Conversation With, we spoke with Dr. Jo-Anne Vergilio the Senior Director in Pathology; Senior Associate Medical Director in Laboratory Operations, and Senior Hematopathologist at Foundation Medicine, Inc. Dr. Vergilio discusses what patients should know about biomarker testing and answers the following questions:

  1. How does biomarker testing work?
  2. How does biomarker testing help a cancer patient’s doctor with determining next steps in treatment?
  3. When in a patient’s course of treatment would they want to get biomarker testing?
  4. What is the difference between different kinds of biomarker tests?
    • Single marker vs. comprehensive
    • Tumor vs. liquid
  5. What does it mean for a biomarker test to be FDA-approved?
  6. If a doctor isn’t offering biomarker testing, what are some things that patients might say to their doctor?

Targeted Therapies: What does it all mean?

When my kids were little, I loved reading to them Arnold Lobel’s Frog and Toad books including “The Corner” in Frog and Toad All Year. In it, Frog assures Toad on a cold, rainy day that spring is just around the corner. Frog says that when he was younger, on a similar cold, rainy day, he searched for spring around many corners until he eventually found it-sunshine and flowers-around the corner of his house.

And so it is with us cancer patients, constantly peering around every corner for the still elusive cure. Researchers at ASCO 2015 offered the most encouraging, hopeful news yet that we won’t have to look around the corner much longer.

Or will we?

Cancer is a tricky disease, in fact many tricky diseases, constantly morphing and exploiting loopholes to outwit us. The buzzwords at this year’s annual meeting in Chicago included “immunotherapy,” combination therapy and “biomarkers.” Immunotherapy has become the fourth arm to battle cancer, after surgery, chemotherapy and radiation. On the upside, scientists are making great strides to develop ways for the body’s immune system to fight the cancer. These are called checkpoint inhibitors. Inhibitors basically release the brakes in cells to allow our immune systems to charge and attack the bad guys, e.g. cancer cells. And since the cancer is being attacked at a molecular level, this should work for everyone. But it doesn’t. And that has proved vexing to researchers. Every specialist with whom PEN spoke at ASCO – from melanoma to lung and prostate cancer to colorectal disease – acknowledges that they don’t yet know why the inhibitors aren’t working for all of us.

That’s where the biomarkers come in. Researchers are working to identify specific markers on an individual’s cell to determine if a specific anti-PD1 or

PD-L1 inhibitor will work on a patient. Or why it won’t work.

For my cancer Chronic Lymphocytic Leukemia, CLL, combination therapy made headline news at ASCO. Through clinical trials, scientists have found that combining a checkpoint inhibitor, Ibrutinib, with a standard chemotherapy called bendamustine along with the monoclonal antibody Rituxan yielded an 80% response rate. That’s a “wow,” but it still isn’t 100%. What is it about the 20% that their bodies resisted the combo therapy?

Maybe the key to unlock the mystery lies with genetics. On the last day of the conference, ASCO announced a joint effort with the NCI, National Cancer Institute, to conduct basket trials. These trials group patients together with specific genetic mutations in a patient’s tumor rather than the location of the tumor. So a prostate cancer patient may achieve complete remission or, dare we say, cure by being treated with a drug developed for breast cancer because of the same genetic mutation found in both.

Will that be the magic bullet that cures cancer? I am optimistic that the answer is just around the corner.