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Which Lung Cancer Treatment Is Right for You? What You Need to Know

Which Lung Cancer Treatment Is Right for You? What You Need to Know from Patient Empowerment Network on Vimeo.

What do you need to know before deciding which treatment is best for YOUR lung cancer? Lung cancer specialist Dr. Heather Wakelee reviews key factors that help guide treatment decisions, including biomarker testing, and shares advice for partnering with your team to advocate for the best care.

Dr. Heather Wakelee is a thoracic medical oncologist and deputy director of the Stanford Cancer Institute where she also serves as the division chief of medical oncology. Learn more about Dr. Wakelee, here.

This program is brought to you by the Patient Empowerment Network. It is made possible through support from Daiichi Sankyo, Foundation Medicine, Illumina, Merck, Novartis, and generous donations from people like you.

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Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for you today’s program. Today, we’re going to discuss how to access the most personalized lung cancer therapy for your individual disease and why patients should insist on essential testing. 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.

Let’s meet our guest today. Joining me is Dr. Heather Wakelee. Dr. Wakelee, would you please introduce yourself?

Dr. Wakelee:              

Sure. Thank you so much and I’m really delighted to be on this and get to address all of our listeners. So, I am Dr. Heather Wakelee and I am a lung cancer specialist. I work at Stanford University where I’m also the chief of the Division of Medical Oncology.

Katherine:                  

Excellent. Thank you. Before we get into an in-depth discussion on lung cancer treatment, we’ve been hearing the term “personalized medicine” a lot more often. How would you define that term?

Dr. Wakelee:              

That’s a great question. So, I think back when I first started taking care of patients living with lung cancer 20 years ago, we really just had chemotherapy for those with metastatic disease. And for those with earlier stage disease, it was just surgery radiation. And since that time, we’ve learned a whole lot and brought in a lot of different types of treatment. Surgery and radiation still have important roles for many patients.

And we think about them as being targeted and personalized based on stage, but it’s a little bit different. When we talk about personalized, we’re thinking more about what are aspects about the tumor that allow us to pick the right systemic treatment. So, “systemic” meaning a pill or something that we give IV.

With chemotherapy, we don’t have much to pick between them as far as specifics for the tumor. We can look at what we call the histology, which is how it looks under the microscope, whether it’s the squamous type or the non-squamous type and some of the chemotherapy drugs matter there. But, in the last 15, 20 years, we’ve learned about the specific what we call “gene mutations” that define the tumor.

And, depending on the gene mutation in the tumor, for some patients, we can give them pill therapy drugs that will work well. So, that’s personalized. Or, immune therapy now is an option for a lot of patients. That’s usually IV therapy.

And, there are some aspects of the tumor that can help us pick that also.

Katherine:                  

Well, I imagine that much of personalized immunotherapy for a patient requires a number of tests and then a thorough review of the results. So, can you provide an overview of important tests following a lung cancer diagnosis?

Dr. Wakelee:              

That’s a fabulous question. When we think about the tests that we need to have done, they’re mostly tests that are done on the tumor, so, either if someone has a surgery or at the time of biopsy. and, that’s where we can figure out what we call, again, the histology that’s squamous or non-squamous. That’s when they look at it under the microscope. But, they also, with the tumor specimen, you can pull the DNA out of the tumor and then test for the gene mutations in the tumor. And, I always emphasize these are not changes in the genes that are in the whole person. They are things that are unique to the tumor. They are what make the tumor different from the rest of the person.

So, we look at those gene mutations or that’s kind of a biomarker. So, there are a lot of terms that we use, and I know it gets really confusing. So, I try to use “biomarker” to mean all of these things, but that gene mutation is what we look at in the tumor tissue to see if there are specific changes that will allow us to give a pill therapy, a targeted pill therapy. And then, there are also aspects of the tumor that help us figure out whether or not the immune therapy might work, and most commonly, that’s something called PD-L1. That’s a protein that we look at on the surface of the tumor, and so again, under the microscope.

Katherine:                  

And, when you talk about extracting DNA, is that via a blood test?

Dr. Wakelee:              

So, we have two different ways to do that. So, what I was talking about before was from the tumor tissue, you can extract the DNA. But now, there are these liquid biopsies where we can draw blood and find the tumor DNA that is different from the rest of the person’s DNA and look for those gene mutations in the tumor.

And that is where there’s a lot of developments happening. And, that’s so fabulous because they’re often faster results for patients, and it means that you can not have to go through another biopsy. We still need the biopsy to establish whether or not there is even cancer. But, once we know that there’s cancer for sure, then we can use the liquid biopsies to get a faster information result on those gene mutations and to follow over time to see how the tumor evolves because tumors change after they’ve been treated.

Katherine:                  

Do you use imaging at all?

Dr. Wakelee:              

Yes. Always. So, when someone is first diagnosed with cancer, we usually find that because of imaging, so, a CT scan or an X-ray, maybe they had a screening CT scan or maybe they had a cough that led someone to go get an X-ray, an examination. So, the imaging is a part of the original diagnosis. And in addition to CT scans, we’ll often get a PET scan that helps us look for, in a different way, the rest of the body, maybe an MRI of the brain to look in that area.

And then, wherever we’ve found the tumor, we will track that area with scans over time. And, it gets a little complicated for a patient that was found with what we call early-stage disease. So, stage I or II. Many of the times, those patients can have surgery and then we don’t have any tumor we can follow anymore. But we get CT scans to look to see if it could have come back. For patients with more advanced disease, so, stage III that couldn’t have surgery or stage IV, there we have areas that we’re going to continue to follow with the scans. And which scans and how often is going to depend a lot on what treatment the patient’s on and where the tumors are located that we’re tracking.

Katherine:                  

Do the.se tests differ for small cell lung cancer and non-small cell lung cancer patients? And, I know that non-small cell lung cancer is also known as NSCLC.

Dr. Wakelee:              

Yes. So, long ago, the only distinction we had with lung cancer was that small cell versus non-small cell, and that is something that is seen under the microscope when that tissue is taken out from the biopsy. The pathology doctors look at it under the microscope, and the cells look different. And, the small cell lung cancer, those cells are small. It’s not very creative naming. And then, everything else is non-small cell or NSCLC. So, it’s SCLC and NSCLC. So, that was one of the first distinctions.

And, it is still very important because the chemotherapy drugs that we use are slightly different. And, the genetic, those gene mutations, we see them in any cancer. That’s what makes a cancer different from the rest of the body. But in small cell lung cancer, the tumor mutations that we see are not things that we know how to target specifically. In non-small cell, there are targets that we can target specifically for some patients.

So, just there, it’s different in having the targeted pill drugs in non-small cell, not so much in small cell. With immune therapy, those newer immune therapy IV drugs, they can work in both small cell and non-small cell. But for small cell, the biomarkers, that PD-L1 level is not as important for helping us figure out who’s going to benefit. For non-small cell, with many of the drugs, it is important. So, there are differences there.

Katherine:                  

Well, let’s go a little deeper. And, you did mention some of this already, Dr. Wakelee, but what is genomic or biomarker testing?

Dr. Wakelee:              

So, we are struggling with how to have one unifying way of describing it because it’s so complicated. So, to me, biomarker testing is any aspect of the tumor that helps us choose the best treatment for that patient. And so, it’s a very broad term. And, within biomarker testing, there are several different ways that we look at it.

So, one is to look at what proteins are on the cell’s surface. And, we do that by having stains that we use to stain the tissue. So again, complicated, but when a piece of tissue is taken out of the person, part of the tumor is removed. It’s sliced into little tiny slices, which are then put on glass slides that can be looked at under the microscope. And, that’s how the pathology doctors can look and see, “Ah, this looks like cancer,” or, “It doesn’t look like cancer.” When it does look like cancer, you can then put on stains, so basically, different colored antibodies that will light up if that particular protein is there. And so, that helps us figure out for sure that this started in the lung because there are specific proteins that are only found in lung. So, that’s one way we used it, and this is an older technology. But, we also can use that to look for how much of this PD-L1 protein is expressed. And so, that’s an important biomarker, but it’s not based on genomics, which is when we’re talking about the DNA.

 Then, we have the genomic testing, and that’s when we’re looking at the genome of the tumor and how that genome is different. And, that’s that DNA or RNA testing. We talk about it with the next-gen sequencing. So, “sequencing,” any of those terms are all meaning we’re looking at some aspect of what makes the tumor genes and therefore the proteins made by the tumor different than the rest of the genes in the person.

And so, that testing, that genomic testing can be done on either the tumor specimen or that’s where we can do blood tests that will be able to pull out those bits of the DNA that are from the tumor versus from the person and help us figure out what’s going on with the cancer. So, when we talk about biomarkers, the whole picture, and when I’m talking with patients who are diagnosed with lung cancer, we talk about well, there’s chemotherapy treatment, which is good for almost everybody. There is targeted therapy.

Targeted therapy is usually based on those genomic tests, and the genomic tests can be done either on the tissue or on blood. But, they’re really important to have a full understanding of the tumors to do a comprehensive or next-gen sequencing analysis of the tumor or DNA. And then, you have the immune therapy where that PD-L1 biomarker is important. So, that’s the way I think about it, and the biomarkers are really critical for helping us figure out what’s the best path forward for any individual patient.

Katherine:                  

Let’s turn to treatment, Dr. Wakelee. On a basic level, what are the goals of treatment for lung cancer?

Dr. Wakelee:              

So, with lung cancer, we’d love to cure everybody, that’s the ultimate goal, and do it in a way where people are able to continue living their life as they were before the cancer diagnosis. The ways that we do it, first of all, we’ve got to find the cancer, and that’s where screening is such an important aspect of things. If we can find the cancer at an earlier stage, we’re more likely to be able to cure someone.

So, what do I mean by “earlier stage?” Well, when a tumor first develops, usually, there is a single cell that develops a mutation, meaning a change in the gene, which gives that cell an advantage so it doesn’t die the way it’s supposed to. And then, it keeps growing, and dividing, and making new cells. And those over time get to a large enough size that they are the cancer. And given more time, those cancer cells start to spread into other parts of the body, usually first into what we call the lymph nodes, and from there then into other organs in the body. And this stage refers to health or how the cancer spread. So, the stage I cancer is still in that ball of cancer. Stage II means that it’s spread into some lymph nodes. Stage III is it spread into more lymph nodes, usually in the center part of the chest or mediastinum, and that’s where it starts to be much more difficult for the surgeons to be able to truly remove all of the cancer.

And then stage IV means that the cancer is not something that we’re going to be able to remove with surgery. It’s spread either within the lung to the lining of the lung or it has spread to other organs in the body. And so, when we talk about those stages that I, II, III, IV, it’s a bit more complicated than that. But, I think for most people, if they just think about it as stage I, just the cancer, stage II, lymph nodes and the lungs, stage III, lymph nodes in the center, and then stage IV, elsewhere, that’s a good way to kind of wrap your head around it.

And when we talk about stage I and II, that’s the truly early stage where we hope to be able to cure people with surgery. Surgery alone is enough for the majority of people with stage I cancer, and for maybe half, a little more than half of people with stage II. So, how can we be better than that? Well, that’s where there’s been a lot of new advances. So, adding chemotherapy after surgery can help a lot of stage II patients.

If the tumor genomic testing biomarkers shows that there’s a mutation called EGFR, we now know that there’s a pill drug that people can take that would prolong the time to when the cancer might come back. And then, just very recently, there was stated that that immune therapy drugs IV can also prolong time to when the cancer comes back and maybe improve cure if the tumor has that biomarker called PD-L1. So, that’s that early stage. So it’s, again, getting more and more complicated and emphasizing that you’ve got to understand the biomarkers of the tumor to know how to best help someone.

When we move to stage III, some have surgery, but when you can’t have surgery, then we do the chemotherapy and the radiation. That’s the key part of the treatment there. And, we also know that immune therapy can be really helpful for a lot of patients when it’s given after the chemo and radiation’s completed. And then for stage IV, I talked about that already, which is you’ve got to do the biomarkers to figure out the best treatments for some people starting with a targeted pill drug is the right thing if their tumor has those right gene mutations.

For other people, immune therapy alone might be an option if the PD-L1 level is very high and they don’t have one of those gene mutations in the tumor. And for a lot of people, chemotherapy or chemotherapy plus immunotherapy is the right strategy.

Katherine:                  

Would you help the audience understand the types of therapy for small cell lung cancer specifically?

Dr. Wakelee:              

Yes. So, small cell still has the same kind of staging, but it’s a little bit more simple. We talk about extensive stage or limited stage. And what that has to do with is we rarely do surgery for small cell. It tends to have spread earlier. There are a few cases where that’s done, but normally, we divide it up into limited or extensive. And when we talk about that, limited is the radiation doctors can get all of the cancer in one radiation field, and then radiation plus chemotherapy is the standard approach to try to cure. If it’s more extensive than that, then it becomes extensive stage.

And, the best treatment are going to be chemotherapy plus those immune therapy drugs added together.

And so, the chemotherapy drugs that we use for non-small cell and small cell, the platinum drugs play a role in all of it. The drug we partner is a little bit different. There’s a drug etoposide we use a lot in small cell and a lot of other options for non-small cell. And then, the immune therapy drugs, there are a lot of options that are fairly similar for both small cell and for non-small cell. 

Katherine:                  

Dr. Wakelee, you mentioned targeted therapies. How do they work?

Dr. Wakelee:               

Targeted therapies are something we can use when we find a specific gene mutation in the tumor. So, I mentioned before that in order for a cancer cell to become cancer, something has to happen to the DNA in the cell.

And, there’s a change or a mutation in the DNA of the cell which leads it to be a cancer. And, a lot of the time, that mutation happens in a specific kind of gene that makes a type of protein called a tyrosine kinase. And for those of you who haven’t studied a lot of science, it’s a word you might not have heard before. But basically, these tyrosine kinases are proteins in the body that make a lot of changes to what’s going on in the rest of the cell. So, they’re sort of what we call regulators. And, one way of thinking about them is like on and off switches. So, normally, their job is to sit and if the right molecule comes around, that turns it on, and then it turns on other proteins in the cell. And if that molecule isn’t there, it’s turned off. So, it’s this on and off switch that does a lot of other aspects of what’s going on in the cell. But, sometimes, a mutation happens. It turns it on all the time. So, it’s like if you leave the light on.

It’s on all the time, that’s using a lot of energy, and that’s actually what’s driving the cell to act like a cancer. And so, we can now look for some of those mutations that turn some of these tyrosine kinases on all the time. But, we’ve also developed drugs that we can use to turn them off. So, if we find this specific gene mutation that’s turning, say, the EGFR protein on all the time, if we find that, we can have the patient take a pill that then turns that off.

And that helps the cancer slow down, some of it die, some of the cancer cells die, but it doesn’t completely wipe it out. It helps the patient for a long time though by shrinking the cancer, helping them feel better because the symptoms are gone, keeping the cancer from growing. But, cancer cells are clever. They continue to divide, they can continue to make new mutations, and eventually, they figure out ways around that. So, when we talk about targeted therapy, it’s a setting where we find the cancer.

In the cancer, we find the gene mutation, it’s in one of these specific types of proteins, genes that make specific protein that turn something on that we can then turn off, and with those pill drugs, we can have a big impact for people.

Katherine:                  

And, what exactly is immunotherapy?

Dr. Wakelee:              

Immunotherapies are treatments that were used to help keep the immune system more active.

So, the immune system is a very complex mechanism. There are cells that their whole job is to figure out and find things that are not us. So, they are looking for bacteria, they’re looking for cells that have a virus in them, and when they find it, they attack. And, that attack can be in the form of antibodies, it can be cells that actually go in and attack other cells directly, and we are all familiar a little bit with the immune system because we know that if we get a cold, our body, we can get a fever, that’s part of our immune response, and we get better. And then, some people know the bad side of the immune system if they have allergies or certain autoimmune diseases where the immune system gets a little bit too revved up and starts to recognize normal things as foreign.

So, in the setting of cancer, normally, the immune system is able to recognize a cancer cell, see that it’s different from the rest, and get rid of it. But, cancer cells are clever and they figure out ways to evade the immune system. And, one of the ways they do this is they put a protein called PD-L1. So, PD-L1 is a protein that a lot of our normal cells use to say, “Just a normal cell. Ignore me.” And so, when an immune cell comes in and sees that, it gets turned off it goes away. So, what our immune therapies do is most of them are blocking that PD-L1 protein. And, when they do that, it’s sort of like taking away the stop sign. So, you’ve got a tumor using a stop sign to say, “Go away, immune cell,” you block it so the immune cells can’t see that stop sign, and so then it kills the cancer cell better. So, that’s how these drugs work, and that’s the immune therapy.

There are some other stop signs besides PD-1 and PD-L1, but that’s the most common. So, when we’re talking about immune therapy, it’s drugs that block that. So, they increase the ability for the immune cell to recognize cancers. The risk from them is that you can get the body to recognize normal tissue as a problem sometimes. So, that’s the toxicity that we watch for.

Katherine:                  

Right. What are the advantages of these new treatment approaches compared to standard chemotherapy?

Dr. Wakelee:              

Well, I think the most exciting news that we’ve seen in lung cancer over the last few years is that we’re actually helping more people live longer. And the way that we’re doing that is through these newer treatments. So, when we can personalize treatment by recognizing that a person’s cancer has a specific gene mutation and we can give them the right targeted pill drug, we can help them live longer and feel better because those often have fewer side effects. Wish I could say they were curing the disease, but they’re helping people live longer.

And, that can be measured in years for some folks, which is fantastic. And then, with immune therapy, again, they’re not working for everybody, but they were for a large number of patients with lung cancer with non-small cell to help them live longer with their cancer controlled. And so, we’ve actually improved the overall survival rates for lung cancer with these new developments. Where we can make even more of an impact is also by finding more of the cancers earlier, and that’s where cancer screening is so important also. So, by having more choices, chemotherapy can still help a lot of people. Targeted therapies can help probably close to 20, 30, 40 percent of people with non-small cell lung cancer that’s the adenocarcinoma type. And then, the immune therapies can help other people living with lung cancer. Usually immune therapies don’t work on the same tumors the way the targeted pills work. So, you’re kind of getting at different groups of people with those different strategies. It’s not completely true, but it’s a kind of general principle about it.

Katherine:                  

What about side effects for some of these treatment choices?

Dr. Wakelee:               

So, chemotherapy is one people fear the most, but I think it has a bit more of a bad reputation than it needs. A lot of the lung cancer therapies that are chemotherapy can be reasonably tolerated. I mean, I’m not signing up to go get chemotherapy just because. There definitely are side effects. The biggest one is people get fatigue, get really tired. Though, if they’re feeling horrible because of the cancer, a lot of times people feel dramatically better. But, tiredness, it can impact appetite a little bit, though cancer does that also. There can be nausea, vomiting, but we’re much better at controlling that with the newer drugs. Some cancer therapies cause hair loss, but a lot of our non-small cell lung cancer therapies don’t cause hair loss. So, there are a lot of options there you can talk about with your doctor. And then, when the blood counts are low, there can be risk for infection, low red blood cells with anemia.

So, there are a lot of different things. But in general, chemotherapy is better tolerated than people think it’s going to be because in the movies, they make it look horrendous.

With the pill therapies, again, lots of variability depending on the specific pill. Some of them cause rash. Some don’t. Some of them can cause some changes to the heart that we have to monitor with EKGs, electrocardiograms, some don’t. Some cause some changes to labs like for liver tests that we have to monitor. Some don’t. Some cause hair color changes. Some don’t. It’s always to gray, unfortunately.

So, there are a lot of different variations in what different treatments can do. And so, it’s just really important if your doctor is talking with you about starting one of the targeted pill drugs that you really ask what are the side effects I need to be watching for, what are the ones I need to know to call you about, and which are the ones I just know, “Okay, this is happening and it’s okay. It’s going to cause swelling in the ankles,” no, just a huge range of them. And then, with the immune therapy drugs, they tend to be mostly fatigue, just like with chemotherapy, though some people feel fine.

What we have to watch for is that they can cause what we call autoimmunity. So, it’s talking about the fact that the way they work is they help the immune system better recognize the cancer, and they do that by taking away one of the stop signals. But, that stop signal, the PD-1, PD-L1, that stop signal is also used by a lot of normal cells to tell the immune system to back off. So, when you remove it, when you block it, the immune system can get confused and start to attack normal cells. So, you can get a rash, people can end up with gut symptoms like diarrhea, they also can end up with it attacking the lungs and causing what we call a pneumonitis lung inflammation or brain symptoms, so, almost anything. Now, those are rare, and we can treat them with steroids. But, people need to be aware that if something new is happening, they need to alert their doctor. I think sometimes, there’s this false impression that immune therapy is completely safe, but, it’s not. And, all of the treatments that I’m talking about are designed to help people live better and live longer when they’re dealing with lung cancer, but they all also have risk.

And so, it’s just really important to have those discussions with the care team as you’re starting something new about what are the things I need to be watching for and to know how to reach people if you’ve got a new and concerning symptom, especially if you’re starting on something new.

Katherine:                  

That’s all really helpful information. Thank you, Dr. Wakelee. We have a question that we received from an audience member earlier. Jeff asks, “How do you know if your lung cancer treatment is working?”

Dr. Wakelee:              

So, there are a lot of ways of knowing if treatment is helping. So, the one I rely on the most is, “Does the patient overall feel better?” That is difficult to say exactly how. Sometimes people are having breathing problems; they feel that that’s better. Sometimes their energy’s lower. They feel better. It can be vague. We also use scans. So, we tend to get scans, depending on the treatment we’re giving, every couple of months plus or minus, sometimes, every three months to help track what’s actually going on. But occasionally, there are discrepancies.

So, sometimes, the scan, is it better? Is it not better? Can’t really tell. And then, you’re always taking that, “How does the patient feel?” So, usually, if the scans are better, the patient feels better. It’s easy. Usually if the patient’s feeling worse and the scan looks worse, clear decision. Not a good one, but clearly, we need to do something different. But sometimes, you’re left, and especially this happens with the first scan because you get a scan, it takes a little while, you start the new treatment, then you get the next scan, how much of the changes happened before you started the new one and how much didn’t? So, these can be more challenging conversations, but generally if the patient’s feeling a little bit better, the scan’s unclear, we usually say, “You know, let’s give this treatment a little bit more time.” We also, I think your question was specifically around how do we tell if it’s working, but, you also often need to be thinking about, “Well, what’s it doing that’s negative to the person and is that potential, those side effects worth the benefits we are or are not seeing?”

So, it’s kind of all of those things together. It can be a bit complex.

Katherine:                  

What goes into the decision to change therapies if it becomes necessary?

Dr. Wakelee:              

So, when we’re thinking about making a change, the way I always look at it is, is where we are today still okay or not? And, if it’s not, that would be because clearly the cancer’s growing or clearly the side effects are just not tolerable. Then, we decide together with the patient we need to do something different. And, when we think about what do we do next, we look at what have we’ve already done, did it work or not, if not, let’s do something more different. And so, let’s think about something that might be somewhat similar. When we’re dealing with targeted therapies, we have ways to try to figure out what changed in the tumor that made it now resistant or not working with that treatment. And so, with some of the pill drugs, there’s been a lot of research and understanding how does the tumor change that helps it evade, get away from, be resistant to whatever treatment you’re on.

And then, sometimes, we have other pill drugs that work in that particular setting, not always. With immune therapy, we’re trying to better understand why does the immune therapy stop working? Sometimes you can add back to it, like, you can add chemotherapy back to immune therapy alone or sometimes you can do radiation with immune therapy to get that response back. Or, add other combinations to it. So, that’s another thing that we’re working on. And then, like I said, if someone hasn’t ever had chemotherapy and the tumor’s become resistant, we’re going to be thinking a lot about chemo because that can play a role against so many different reasons that the cancer might not be responding to whatever treatments someone’s on. And then also, looking at how the patient’s feeling and doing, what their overall what we call “performance status, ” their sort of overall health, and how well do we feel with them that they’re going to be able to tolerate the next treatment because, you’re always having to weigh how much is this likely to help, and how might this harm in finding the right balance.

Katherine:                  

I’d be remiss if I did not bring up COVID-19, and, I’m sure a lot of patients are curious whether the vaccine is safe and effective.

Dr. Wakelee:              

So, we do believe the vaccine is safe and effective for patients living with lung cancer, and really important to be protected as much as possible. I was part of a group of other physicians around the world looking at the impact of COVID-19 on patients living with lung cancer. And, we collaborated with a group of physicians, Rayna Garcina was the lead. She was living in northern Italy at the time of the first wave, and so, was really face-to-face with it early on when there was so much we didn’t know. And, she gathered a group of us to watch and see, and what we were able to figure out before the vaccine was available was that people living with lung cancer who were overall healthy still except for their cancer were perhaps on a pill, targeted therapy, or immune therapy seemed to really not have that different of an impact compared to people who didn’t have lung cancer.

Chemotherapy was a little bit harder to see that, but didn’t seem to be such a big issue. It’s different than people living with, say, leukemias or lymphomas where the treatments are impacting their immune systems even more. They seem to have worse outcomes. A lot of lung cancer patients were okay, but still, it’s a higher risk. And so, we want to protect our patients as much as possible.

So, we are, now that we have the vaccines, strongly advocating vaccines for any patient who was living with cancer really for almost anybody because as a physician, we really think that makes a big impact. We have not seen any negative impacts of the vaccine on any aspect of cancer treatment. It does not have a negative impact on how well the cancer is treated by the therapies. We did notice that when someone gets the vaccine, they can get some enlargement of the lymph nodes. That’s part of having an immune response is your lymph nodes get enlarged. And so, we did get a bunch of scans that the vaccines came out showing, “Well, this person has some lymph nodes in the axilla, which is the armpit.”

And it seemed to be correlating with the side that someone had a vaccine. And then, those go away. And, this was actually an interesting medical literature thing because for people getting screened with mammograms for breast cancer, there were suddenly all these lymph nodes showing up. But that was actually a sign that the person was responding to the vaccine and it went away over time. And, it was a fine thing. It was just – I remember the first patient I had where that happened, we’re like, “Oh, well, that makes sense. Okay.” So, it’s okay. So, it was not cancer. It was just the immune response. But, yeah, so, we are recommending vaccines. There’s no data showing it is not working for lung cancer patients. The vaccines are less effective in people getting certain types of cancer treatment that are really suppressing the immune system. But even some response is better than none, and we’re still recommending the patients really do their best to stay safe with masks and things like that.

Katherine:                  

Dr. Wakelee, what are you excited about in lung cancer research right now? And, what do you want to leave the audience with? Are you hopeful?

Dr. Wakelee:              

I’m very hopeful. When I started treating lung cancer patients 20 years ago, we only had chemotherapy. And now, for metastatic disease, with using the right biomarkers, we can figure out so much more about the cancer to be able to personalize the treatment, for many patients, being able to offer pill therapies that are somewhat less toxic and highly active and give people more time. And now, we’re in the immune therapy revolution, which is helping a whole other group of patients living with lung cancer to be able to live with quality life for much longer. And the pace of discovery is just going up so quickly. And, I think that’s what I’m most hopeful about is just how much attention is being paid on lung cancer and finding better therapies that are going to help more people for a longer period of time. And again, I’m going to emphasize the screening is making a big difference also. If we can find the disease early, we can have an even bigger impact on people.

Katherine:                  

Dr. Wakelee, thank you so much for joining us today.

Dr. Wakelee:              

Thank you. Really enjoyed talking with you. Thank you.

Katherine:                   

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 joining us today.

How Is AML Treatment Effectiveness Monitored?

How Is AML Treatment Effectiveness Monitored? from Patient Empowerment Network on Vimeo.

How can acute myeloid leukemia (AML) treatment effectiveness be monitored over time? Expert Dr. Ellen Ritchie explains when testing is typically done following AML treatment, which methods are used for monitoring, and when retesting may be appropriate.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

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Key AML Testing for Better Care: Understanding Prognosis and Treatment Choices

Transcript:

Katherine:

Once a patient has begun treatment, how do you monitor whether it’s working?

Dr. Ritchie:

So, one of the more frustrating things about being an AML patient, is you don’t know right off the bat whether or not that you have gone into remission. So, what happens is you receive the chemotherapy, and the day you start chemotherapy is really day one. And somewhere around day 14, you’re at your lowest point. So, your blood counts are low, and you often feel really terrible, and you really wonder, is this working? But unfortunately, I can’t really tell you. Some institutions do bone marrow biopsies if you have intensive chemotherapy on day 14, or if you’re getting venetoclax (Venclexta) therapy somewhere around day 21 to look and see whether they still see leukemia cells, but the utility of that is different per institution.

The real test of whether chemotherapy x, is at the end of about 28-35 days, are your blood counts coming up, and are you making normal blood cells. Are you making platelets, which are the part of the blood that clots the blood? Or are you making neutrophils, which are the important cells needed to help you fight infection. So, the real proof of a remission, is are your platelets over 100,000? Is your neutrophil count over 1,000? And when we look in the bone marrow around that time, do we see normal cells developing and no leukemia?

Katherine:

How often should testing take place? And should patients be retested over time?

Dr. Ritchie:

So, the bone marrow biopsy is done frequently once you have a diagnosis of acute leukemia. So certainly, it’s done upon diagnosis of the disease.

And as I mentioned earlier in certain institutions, about halfway through your chemotherapy cycle, they’ll do a bone marrow biopsy to see whether or not they see any residual leukemia cells. That’s not done everywhere, and it’s done differently depending upon institutions sometimes. At the end of the chemotherapy treatment, if you recover your blood counts, we do a bone marrow biopsy to confirm a remission. If by day 35, we haven’t seen that your blood counts are recovering, we may do a bone marrow biopsy to see whether or not we see leukemia cells in there, or early recovery. So, you’re definitely going to have bone marrows at those time points. If you’ve gone into remission, it depends on what we’d do next as to when you would have another bone marrow biopsy. So, if you’re going to bone marrow transplant you may have one more biopsy, just prior to going into transplant, and another biopsy at the end of the first month after transplant.

If you’re going to have what we call ongoing therapy, roughly every three or four months, we may do a bone marrow biopsy to determine whether or not the remission is holding. If during ongoing therapy, we see that there is blood count abnormalities that we weren’t expecting, that might be a reason that we would do a bone marrow biopsy. And that’s unpredictable as to when that would be.

Is the COVID-19 Vaccine Safe and Effective for AML Patients?

Is the COVID-19 Vaccine Safe and Effective for AML Patients? from Patient Empowerment Network on Vimeo.

What should acute myeloid leukemia (AML) patients know about COVID-19 vaccines? Expert Dr. Ellen Ritchie shares information about COVID-19 vaccine safety and effectiveness for AML patients and reviews side effects that may follow vaccination.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

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Transcript:

Katherine:

The second question is from Craig, he says, “I’m currently undergoing treatment for AML. Is the COVID-19 vaccine safe and effective?”

Dr. Ritchie:

I recommend the COVID-19 vaccine to everyone, all my patients. A little immunity is better than none. And there is preliminary data, looking at patients with myeloid malignancies, not lymphoid, but myeloid malignancies, where it appears there is an immune response to the COVID-19 vaccine. So, I would suggest that you get the COVID-19 vaccine. Any of them that are available, are good. Whether it’s Moderna, or Pfizer, or Johnson & Johnson. Whatever is available to you, you should go ahead and get.

Katherine:

Are there any symptoms or issues that AML patients should be looking for post-vaccine?

Dr. Ritchie:

Post-vaccine, there’s a lot of symptoms that people have. And they can be similar among myeloid patients. Some of my patients have had no reaction whatsoever, some people have had a really sore arm.

Some patients are incredibly tired after the vaccine; some patients develop a low-grade fever for a couple of days. Those are really what we watch for. Sometimes when there’s a reaction, we’re hopeful that there’s an antibody being made, or an immune response that’s developing. So, it’s not always a bad thing if you have a reaction. But I don’t think that the reactions of patients of myeloid malignancies is any different than that of the general public.

How to Be a Partner in Your AML Care

How to Be a Partner in Your AML Care from Patient Empowerment Network on Vimeo.

How can acute myeloid leukemia (AML) patients take a proactive approach to their care? Expert Dr. Ellen Ritchie shares advice for qualities to look for in your AML care provider and how to ensure all your questions are answered by your healthcare team.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

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Being Pro-Active in Your Care: Key AML Testing to Advocate For

Advocating for Key AML Testing: Advice From an Expert

Advocating for Key AML Testing: Advice From an Expert

Transcript:

Katherine:

Dr. Ritchie, what advice do you have for patients to help them feel more confident in speaking up and advocating, being a partner in their care?

Dr. Ritchie:

Well, when you choose a leukemia doctor, you need to choose someone that you can actually communicate with. Someone who you feel is not allowing you to ask questions, or is not curious about what your life is like, you may want to think, I want to check out somebody else.

Because it’s really important you like the person who’s your doctor, and that you have a trust relationship together. So, it’s really – I tell some patients it’s a marriage of convenience that we have. And that you really have to think of it that way. If someone doesn’t allow you to ask questions or if they are not fully answering your questions in a way that you understand, try and speak up for yourself and make sure that the doctor tries to address that. And if the doctor won’t address those things for you, or you feel like you don’t understand what is being explained to you, then you can think about trying to see someone else. I think it’s really important if you can, to write down as many questions as you have about your disease before you come in.

Because often what happens is you get there, you’re stunned by the amount of information, and the questions you wanted to ask, you forget. And the next day, you’re like, “Ugh, I didn’t ask these questions.” So, before you come in, if you write questions. Questions about insurance coverage, that may not be something that we go over. Or questions about toxicities, or questions, “If I’m going to lose my hair, do you have the name of a wig facility?” All these questions that you might have, put them on a piece of paper, so that they can be addressed when you’re with the doctor. And other things will come up, you’ll have other questions when you’re there, but make sure your fundamental questions are answered.

What Is Low-Intensity AML Therapy?

What Is Low-Intensity AML Therapy? from Patient Empowerment Network on Vimeo.

How does low-intensity AML therapy differ from high-intensity AML therapy? Expert Dr. Ellen Ritchie provides a comparison of the administration methods, side effects and reviews which AML patients low-intensity and high-intensity therapy are right for.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

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Transcript:

Katherine:

You mentioned earlier, Dr. Ritchie, low-intensity therapy. Could you tell us about the types of treatment options?

Dr. Ritchie:

So, I’ll go – high-intensity therapy or intense chemotherapy always has to be given really in a hospital. And if you don’t start it – if you can start certain intensive chemotherapies, like daunorubicin and cytarabine (Vyxeos), which is also intensive, in the outpatient setting, but by day seven or eight, you end up in the hospital. And in intensive chemotherapies, you lose your hair, there’s GI toxicities, you’re at high risk of developing infections and you need a lot of transfusion. And for even young people, it’s a difficult therapy for which you’re in the hospital, and 90-some percent of patients are on IV antibiotics.

So, it’s intensive chemotherapy because it has to be given in a hospital setting and requires intensive supportive care. Low-intensity therapy can be given in the outpatient setting. So, at the present time you can get a drug like azacitidine (Vidaza), for example, which is an injection that you get seven days in a row.

Unfortunately, you have to come to the doctor’s office every day for those injections, but once you’ve had the injection, you can go home. Combined with venetoclax (Venclexta) which is an oral agent. So, an oral agent can be given at home.

You need close supervision in the physician’s office when you’re on this type of therapy, but you don’t need the constant support that you need if you are getting intensive chemotherapy. So, it can be done, in the comfort really of your home and with your family. You will have to come in and have transfusions potentially as an outpatient, nearly everyone does. And there’s always the risk that you develop a fever and if you do, you have to come into the hospital for IV antibiotics.

But in general, low-intensity means not so much support needed in a hospitalized setting, and the tolerability of this particular chemotherapy in the outpatient setting.

AML Targeted Therapies, What’s Available and How Do They Work?

AML Targeted Therapies, What’s Available and How Do They Work? from Patient Empowerment Network on Vimeo.

There are several targeted therapies approved for the treatment of acute myeloid leukemia (AML). Expert Dr. Ellen Ritchie provides insight about recent approvals, how these therapies work, and shares details about newer therapies currently being studied for the treatment of AML.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

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Transcript:

Katherine:

You touched upon this earlier, but what targeted therapies or treatments are available for AML patients?

Dr. Ritchie:

So, there have been many recent FDA approvals of drugs that are targeted. One, is the FLT3 inhibitors. And the two that are available are Midostaurin, which is most commonly – was the first drug that was really added to intensive chemotherapy.

And clinical trials show that in those FLT3-positive population that patients had an overall better outcome if midostaurin (Rydapt) were added to intensive chemotherapy. There’s also a drug called gilteritinib (Xospata), and this drug is also a FLT3 inhibitor that was tested in patients who had refractory leukemia. They could either get real chemotherapy regimen or they could get gilteritinib. And it turns out in the FLT3-positive patients, the gilteritinib was superior to the strong chemotherapy. So that’s been approved for patients who have refractory, or disease that didn’t really respond to initial therapy, that is IDH – or is FLT3-positive.

Then there’s the IDH1 and IDH2 inhibitors that have also been approved, and a small proportion of AML patients will be positive for IDH1 or IDH2 mutations.

The IDH1 inhibitor ivosidenib (Tibsovo), is available and can be used to treat patients if you know up front, they have an IDH1 inhibitor. So, that’s a regimen where the single agent can be used to treat an IDH1 mutated patient who’s newly diagnosed. Those patients are also eligible for many clinical trials now, where they’re combining that particular drug with other agents, in an effort to improve outcome. For IDH2 positive patients, there’s a drug called enasidenib (Idhifa). And this drug is used mainly in patients in the second line setting. But it specifically targets IDH2. And patients go into remission sometimes for a prolonged period of time. So, these drugs are FDA approved, and they’re treating targetable mutations.

TP53 mutations are a particularly bothersome mutation because it confers a poor outcome. And I’m happy to say that we have clinical trials now that are available that actually target TP53 mutations.

So, there are – there is therapy available for that type of mutation that was

not available before through the clinical trials. And I expect in coming years that we’re going to see more and more targeted therapies develop in AML which can be used potentially in combination with what we’re already using as backbones to enhance the outcome of patients with this disease.

Katherine:

Well, how do targeted therapies work?

Dr. Ritchie:

So, targeted therapies work on – it’s sort of complicated. The targets which are available, IDH or the FLT3 is really on the outside of the cell and it is a drug which is targeted directly to the FLT3 on the outside of the cell.

It works quite well in the peripheral blood, where you see the blast oftentimes disappear. The big concern always is how well it’s working getting deep into the marrow. But it’s looking at the target on the outside of the cell. IDH1 and IDH2 inhibitors work on particular chemicals which are involved in the kreb cycle, and those of you that took high school chemistry may have memories buried in the deep parts of your brain of learning the kreb cycle. And this is a fundamental metabolic cycle inside cells, and if you have a mutation, an IDH1 or IDH2, you’re unable to go through that full kreb cycle in the appropriate way. And that is something that leads to you having a cancer, in this case AML. So, these drugs actually interfere with what’s happening in that kreb cycle, and allow you to make more normal cells.

Factors to Consider When Choosing an AML Treatment

Factors to Consider When Choosing an AML Treatment from Patient Empowerment Network on Vimeo.

What test results and factors should be considered when choosing an acute myeloid leukemia (AML) treatment? Expert Dr. Ellen Ritchie explains how test results impact AML prognosis and treatment – and other factors that come into play when determining a treatment approach.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

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Transcript:

Katherine:

How do the results of these tests affect prognosis and treatment?

Dr. Ritchie:

Well, when a patient has AML, if they are a fit patient, if it will help us determine after initial induction, whether to cure the patient we need to do a bone marrow transplant, or we can just continue with chemotherapy.

And those are really important things to determine. So, if you have a good prognosis AML, if you have an AML that has certain translocations like inversion 16 or 821, or if you have a CEPBA mutation or you have an NPM1 mutation, and that’s all you have, you may do particularly well with chemotherapy treatment alone. And you won’t need to have a bone marrow transplant.

If you have certain other mutations, we know that the only way that we’re going to cure you, is with a bone marrow transplant. And if you are fit, when we finish induction and even as we’re doing induction, we’re preparing you for a bone marrow transplant down the line.

One disadvantage, just to mention about the molecular testing, is it doesn’t come back as quickly as some of the other testing. So that you will have already started induction chemotherapy most generally before the mutational testing comes back. Which can be anywhere – depending upon the institution, between seven and 21 days. So, it takes time for those results to be available.

Katherine:

Outside of test results, Dr. Ritchie, what other factors should be considered when choosing treatment?

Dr. Ritchie:

So, you want to choose whether a patient is most likely to benefit from intense induction chemotherapy. With strong chemotherapies where the backbone of those therapies would be an anthracycline, like daunorubicin (Cerubidine) or cytarabine (Liposomal), or daunorubicin or idarubicin (Idamycin PFS), together with cytarabine. And these are intensive chemotherapies. Versus, non-intensive chemotherapy which is able to be done as an outpatient, more frequently. And it is something that is gentler for a patient, they’re less likely to have severe toxicity. And the backbone of those regimens is using a drug called azacitidine (Vidaza) or decitabine (Inqovi), together with a second drug called venetoclax (Venclexta).

So, these are the two backbones, there may be clinical trials or there may be targetable aspects of your leukemia, which drugs would be added to either of those backbones. But those are the two backbones. And I also like to identify those patients that may not benefit from chemotherapy at all. And so, it’s very important, I think to really get to know your patient. And I spend time with my patient, particularly on the first visit, to understand not only their physical health, but their mental health. How good is their cognition, what is their mood, are they depressed, or are they happy people? And what is their circumstance? Do they have people to support them? Do they live close to family? Is a caregiver able to come, with an elderly patient for example, to visits?

Those, and whether or not they’re living alone and need tremendous support. So that’s really important to determine and helps me to choose what the best therapy might be. And also, concurrently what I can do to shore up the patient to do better with whatever therapy that I’m giving them. I.e., if you’re depressed, let’s work on that, or if your blood pressure is too high, or if you are – your diabetes is out of control at the same time that I’m seeing you, to try and fix those particular problems. In older patients I often do sort of a miniature version of the geriatric assessment. And in trials that have been so far, the most important aspects of the geriatric assessment, are really what is your cognitive function? Do have a mild dementia, or do you not have a mild dementia? Because dementia may be or mild dementia may be associated with poorer outcome.

The other is, are you able to do what we call the incidental tasks of daily life. So, you know fundamental tasks are really brushing your teeth and combing your hair, and dressing yourself. But are you able to do your cooking and your shopping and your banking and those things? Patients who have trouble doing their cooking and shopping and banking, and those types of activities, that also has been associated with a poor overall survival in AML. So, it’s really important to determine all of those aspects and if there are any deficiencies, to really know that the only therapeutic choice for that particular patient would be a low-intensity therapy.

Understanding Key Tests That Affect AML Treatment Choices

Understanding Key Tests That Affect AML Treatment Choices from Patient Empowerment Network on Vimeo.

For acute myeloid leukemia (AML), test results play a vital role in determining the most appropriate treatment option. Expert Dr. Ellen Ritchie reviews key tests used to pinpoint a patient’s specific AML, how the test results are utilized, and important questions patients should ask their doctor about AML testing. 

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

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Essential Testing in AML: How Results Impact Care & Treatment Choices


Transcript:

Katherine:

So, let’s help our audience be clear about basic testing. What tests are necessary to help understand a patient’s specific disease at diagnosis?

Dr. Ritchie:

I mean certainly it’s important to do a physical exam and to find out what the general health of the patient is. In order to evaluate an AML, or any other leukemia, I look at the peripheral blood smear. To look at what I think the type of leukemia might be that I am dealing with. There are some leukemias that have particular way that they look like acute promyelocytic leukemia for which there is a designated therapy which works.

And you can tell that just by looking at a peripheral blood slide. The next test is always a bone marrow biopsy. Patients are not delighted that that is a test, but it is a test that can be done in the office, usually within 15 to 20 minutes. And that test gives us a lot of information. It gives us information about what type of AML it is, what are the markers on the outside of the cell, it gives us information about the chromosomes inside the leukemia cell. Are there missing chromosomes, or rearranged chromosomes? And if there are, that can be very relevant to the prognosis. And lastly, it’s sent for a particular mutations or markers. So, we look for IDH3 mutations, we look for FLT3 mutations, we look for IDH1 and IDH2 mutations, and we do an entire myeloid panel. Which is about 44/45 genes that are most commonly mutated in patients with AML. So that’s the initial work-up for any AML patient.

Katherine:

You mentioned markers, Dr. Ritchie. What is genomic, or biomarker testing?

Dr. Ritchie:

So, we’re looking really at most specifically at mutations inside individual genes that might be in your leukemia cell. So, there are some mutations actually that confer a better prognosis. Like NPM1 or CEPBA, those can be more positive type of prognosis than some of the others.

But we’re also looking for markers that might be targetable with certain therapies that we have. So, if you have a FLT3 ITD or TKD, we actually have particular drugs which can target those particular mutations. There are also drugs that are FDA approved to treat IDH1 and IDH2 mutations.

There are certain mutations that have a relatively poor prognosis, like TP53 for which there are clinical trials which are available, which specifically are meant to target patients who have those sorts of mutations. And there’re other clinical trials using the FDA-approved drugs that I just mentioned, for FLT3, for IDH1 and IDH2 and combining it with other agents to try and improve outcome in AML patients.

Katherine:

Some patients may not know if they’ve received these important tests, so what key questions should they be asking their physician about testing?

Dr. Ritchie:

So, physicians, they – financial coverage of the mutational testing is not uniform across the country and across insurances. So, Medicare and different Medicare insurances and some of the private insurances all vary in their coverage.

So, in my clinic, I am asking – I prefer the test that we do in house at Cornell. But it’s important that I ask, what will their insurance cover. And make sure that I send the appropriate testing that will be covered by insurance. There are some insurances that will not cover this type of testing. So, it is a real question for the patient, when you go to see the doctor to say, are you going to do mutational NGS testing?

And, will my insurance cover this? Hopefully most – if Medicare adopts the coverage of these types of mutational testing, it’s often true that private insurance will eventually pick this up. But it’s a murky field, and it’s really important to talk to your doctor about this. The cost of the bone marrow biopsy, and the chromosomal evaluation is nearly always covered by insurance.

Understanding Personalized Medicine for AML

Understanding Personalized Medicine for AML from Patient Empowerment Network on Vimeo.

What should you know before deciding on treatment for YOUR AML? AML specialist Dr. Ellen Ritchie reviews key factors that guide treatment choices, including biomarker testing results, and shares advice for partnering with your team to advocate for the best care.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

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Transcript:

Katherine:

As we begin to talk about personalized therapy and AML, let’s start with the basics. How would you define personalized medicine?

Dr. Ritchie:

Personalized medicine, to me is really, it’s a difficult question. It’s trying to find the best treatment for a particular patient. And it’s looking at biologic issues, what kind of cancer, what type of AML is it, what are the specific mutations or chromosomal abnormalities. But it’s also looking at the person. Is the patient active or not active? Do they have lots of other diseases like diabetes and coronary artery disease? Or pulmonary disease, or are they completely healthy?

Or, do they have support at home? If they’re sick at home is there someone who can take care of them, versus a situation where you’re older and alone and you have no real family member to rely on. So, all of these things are very important in making a personalized decision as to how you treat a patient.

Where Do Clinical Trials Fit Into an AML Treatment Plan?

Where Do Clinical Trials Fit Into an AML Treatment Plan? from Patient Empowerment Network on Vimeo.

AML expert Dr. Eunice Wang discusses the role that clinical trials play in advancing research, the benefits of participation in research, and explains why she recommends trials for AML patients. 

Dr. Eunice Wang is the Chief of the Leukemia Service and Professor of Oncology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Wang, here.

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Transcript:

Katherine:

Where do clinical trials fit in when it comes to choosing treatment?

Dr. Wang:

Clinical trials are the mainstay of everything that we do in cancer care. Every single cancer drug that we’ve developed dating back into the 1970s at the National Institute of Health is the result of some patients and some doctors designing a clinical trial. These FLT3 inhibitors were developed over the last several years, so when I first came out of fellowship and started my training, we didn’t have these targeted therapies. Since 2017, in four years, we’ve had nine different drugs approved.

So, clinical trials are the way that we go from a finding in the laboratory to somebody having an extra birthday or going to their son or daughter’s wedding. That’s really how important it is, and those brave individuals who participate in clinical trials are helping not only themselves, but helping other people. I can’t tell you how many patients I enroll in clinical trials for AML, and I have told them – I said, “These nine drugs that we approved were because of nine different clinical trials which demonstrated benefit involving hundreds of thousands of patients.”

I can’t tell you how many times I’ve had a patient say to me, “Look, doctor, I’m going to participate in this clinical trial so that even if I’m not helped, you could learn something from me that could help the next person with their disease.” People are incredibly unselfish when it comes to clinical trials. I recommend a clinical trial for all my patients because I feel like that’s the cutting-edge clinical care.

I had patients here who I had on clinical trial drugs, and I was able to go to them and say, “Good news: Your drug has now been approved.” And, they say, “Doctor, why? I’ve been on this drug for a year.” And, I said, “That’s right, because you were part of that clinical trial, and you’re here now because of that drug, and now, a year or two later, that drug’s potency has been recognized, and now, the fact that you were in that trial has really helped us get this approval, which is going to help every other patient with that disease going down the line.” So, very important.

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

Shared Decision-Making, Advice for Partnering With Your AML from Patient Empowerment Network on Vimeo.

AML expert Dr. Eunice Wang reviews how shared decision-making impacts overall care by keeping the individual patient and their unique circumstance in mind when determining a treatment path. Dr. Wang discusses the importance of reviewing clinical factors as well as having honest conversations, giving the patient a voice in their care. 

Dr. Eunice Wang is the Chief of the Leukemia Service and Professor of Oncology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Wang, here.

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Transcript:

Katherine:

We’ve been hearing a lot lately about shared decision-making. In your opinion, how is this concept best put into practice?

Dr. Wang:

So, shared decision-making is the process where the physician is no longer dictating the care, and telling patients, “This is the best therapy for you,” and just plowing forward with it. Shared decision-making is really what we want in all of our relationships in our lives, which is sitting down and incorporating many points of view, including both the patient’s wishes and desires as well as those that he or she feels is important to his or her care.

It involves time. It does – it may involve multiple clinic visits. It involves sitting back and having the physician say, “This is the information, this is the data. What is important to you? What is going to work with your particular home situation and family situation and dynamic?”, and then, together, coming up with a decision about care that is individualized for the patient. We talked about individualizing the targeted therapy for the biology of the disease.

Shared decision-making is individualizing the treatment decision for the individual patient and their particular circumstance, and that is best done by sitting down with the patient, looking them in the face, not by looking at your phone, or staring at that computer screen, or reading off some diagnosis from a piece of paper. It’s really involving having those honest conversations.

That’s how things used to always be in medicine, is that it always used to be a decision where the doctor and you would talk and come to a decision, potentially. We’ve kind of gotten away from that with all the electronics and technology, and I think the shared decision-making is a conscious effort by individuals and groups to bring that back in case. It’s very important for AML. AML is a disease that affects largely older individuals, so if you’re in your 60s and 70s and 80s, I can tell you right now that each one of those individuals who have lived decades of life have a certain way that they want to live whatever time they have left.

Katherine:

Of course. Well, when considering a treatment plan, what key questions should patients be asking?

Dr. Wang:

They should be asking – it should be – they should be asking, “How is this going to affect my daily life?” They should be asking questions – “Do I have to be in the hospital? How – do I need to come to the clinic? If I have to come to the clinic, how many times do I have to come to the clinic?”

In my part of the world, it – sometimes even the season in which they’re being diagnosed can impact what disease treatment they want because certain times of the year, travel back and forth in different weather conditions can be difficult. They need to be asking not the question of – that we get asked a lot like, “What would you do if this was your father or your mother?”, but I wouldn’t know.

I turn that around and I say, “But, you’re not my father and you’re not my mother, and if you were my father or my mother, I would ask my father or my mother, ‘What is going to work for you? What are your goals? Do you want aggressive therapy? Do you want to go for high risk/high benefit, or do you want something that’s just going to make you be able to be outpatient for longer, and really what is the most important thing for you and your family right now when we look ahead as to the treatment path?’”

Katherine:

Why is it important for patients to feel like they have a voice in their treatment decisions?

Dr. Wang:

It’s important for them to have a voice in their treatment decision because it is their – first of all, it’s their life, it’s their body. They are the ones that are going to be getting the therapy, suffering the consequences, and making the decisions that can impact not only them, but their loved ones, so – and, I find that the more they understand the disease process, the more they understand and can communicate to me their wishes, the more satisfied we are in care. I’ve had individuals tell me early on in the process where maybe, in a different patient, I would have suggested a second or third treatment – I’ve had them say to me, “I’m done. I’m not – thank you very much.” And, we all have to respect that.

It makes people more satisfied with their care. It makes people feel like they are making – they are guiding the path. They’re not just doing what their husband wants or what their doctor wants. I never want to have a patient say, “Well, I went and got chemo, Dr. Wang, because you wanted me to get chemo.” I don’t want you to get chemo, and I feel like if you have that understanding, I think patients are much more likely to pursue therapy and for the therapy, I think, to be successful or not. But, regardless of whether it’s successful medically, it needs to be successful emotionally for that patient and for that family.

AML Research and Emerging Treatment Options: An Expert’s Perspective

AML Research and Emerging Treatment Options: An Expert’s Perspective from Patient Empowerment Network on Vimeo.

AML expert Dr. Eunice Wang shares exciting advances in the field of AML research, particularly in targeted therapies related to the TP53 and NPM1 mutations. 

Dr. Eunice Wang is the Chief of the Leukemia Service and Professor of Oncology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Wang, here.

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Transcript:

Katherine:

What specifically are you excited about in terms of AML research and emerging treatment options?

Dr. Wang:

I am really excited about the advent of newer targeted therapies. Right now, we only have targeted therapies for probably about three mutations out of the many, many mutations that we know exist in AML. So, we know that there certainly are patients that have specific mutations, such as TP53 mutations, or patients who have very complicated series of DNA damage, that just don’t do well with any of our therapies.

I’m looking forward to another bunch of targeted therapies – these inhibitors called menin inhibitors – that might be useful for treating patients that have mutations in NPM1 gene or other chromosome abnormalities.

I’m also really looking forward to us being able to finally unleash the power of the immune system for treatment of AML with a few novel agents coming down the pike which have, for the first time, started to show that immune modulation can work in AML patients.

What Key Tests Do You Need Before Choosing an AML Treatment?

What Key Tests Do You Need Before Choosing an AML Treatment? from Patient Empowerment Network on Vimeo.

How do test results influence treatment choices for AML? Dr. Eunice Wang shares information about essential testing and explains how results aid in determining the best personalized treatment option for each patient.

Dr. Eunice Wang is the Chief of the Leukemia Service and Professor of Oncology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Wang, here.

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Transcript:

Katherine:

What is the role of testing when deciding on treatment for AML?

Dr. Wang:

Testing is essential in us selecting and determining the best personalized treatment option for each individual patient. As you know, AML is an aggressive hematologic malignancy and can be devastating, both in its life-threatening nature and in its rapidity and the need for a rapid diagnosis. Testing, including both pathology results as well as protein marker testing, and, importantly in this day and age, DNA and RNA testing is essential because we have numerous different treatment options that could be available to the patient if their particular disease biology matches with the targeted therapies that we have.

So, as you may or may not know, since 2017, we’ve had eight or nine different therapies approved for AML, and this is a bonanza of options, some of which are only for specific biological subsets, and some even for specific patients, such as those above the age of 75. So, doing that testing, particularly that genetic testing, is important both in establishing the diagnosis and determining whether there is less toxic, more targeted, personalized treatment approaches, some of which involve low-dose chemo or even pills available to the individual patient.

Katherine:

You’ve answered this, in part, but which tests are essential following an AML diagnosis?

Dr. Wang:

I think all of them are essential, but in this day and age, for the selection of targeted therapy, it really is the mutational testing, which is looking at the RNA of the tumor cells and determining whether that has been altered in allowing the cells to express abnormal proteins. For standard chemotherapy, we also use DNA testing, which is looking at the different chromosomes and seeing whether there’s breakages or what we call translocations, pieces of chromosomes that have been swapped. That DNA chromosome information can give us some insight into prognosis and therapy response.

So, nowadays, it’s not just determining that you have acute leukemia, but looking at the specific DNA and RNA changes, and I have to say that this is a disease that we’re really not seeing any RNA or mutational changes occurring in more than 20 percent or 30 percent of patients. So all of the mutations that we see that could be impactful really don’t occur in more than 20 percent or 30 percent, and could only occur in five or one percent.

So, really, personalizing an individual patient’s disease, both for the disease biology as well as the person that’s getting the chemotherapy or the diagnosis, is really, really important.

Katherine:

Yeah. Let’s define a few terms that are often confusing for patients. What are biomarkers?

Dr. Wang:

Biomarkers are either proteins or expression levels on the cancer cells that can serve to tell us information about the biology of the disease. Okay, so, for example, if you have evidence of residual tumor proteins in your blood, that could be a marker, for example, of minimal residual disease, okay? And, that can tell you maybe one in a million cells have that biomarker, and then you can tell that those one-in-a-million cells are leukemia cells.

So, they’re any marker that we’re using that’s specific for the tumor that can help us in predicting or finding or locating or determining if a tumor would respond to a certain therapy.

Katherine:

What is biomarker testing?

Dr. Wang:

Biomarker testing can be done in many ways. For example, biomarker testing is drawing a sample from the patient and evaluating a marker that we think is going to predict for the disease type.

So, for example, in some cancers, we don’t want to biopsy the lung mass or the tumor mass every single time to see whether it’s shrinking, or getting smaller, or responding. So, in those patients, sometimes we’ll draw a blood sample, and we’ll look for a surrogate marker – some protein that’s expressed in the blood or some DNA or RNA in the blood that is a surrogate or a marker of the tumor so you don’t have to directly biopsy it.

In acute myeloid leukemia, we are looking for – like I said – particular cells in the blood that have particular proteins, and we measure those rather than going ahead and doing that bone marrow biopsy or biopsying those tumors. So, generally, in leukemia, it involves drawing blood samples – that’s the most common; it is a bloodborne disease.

Sometimes, we actually have to go into the bone marrow and do a bone marrow sample, but those biomarkers, as I said, can really improve our ability to detect very, very low levels of disease. So, for example, using a conventional bone marrow biopsy, we can only really detect 1 out of 200 cancer cells by normal – just by visual looking at, but by measuring biomarkers and mutations and other abnormal proteins, we can improve that to 1 in 100,000 cells.

So, really, these biomarkers are very sensitive and important because we want to detect the disease at a point where it’s very, very low. We don’t want to wait until the disease gets very advanced, in which case we think our therapies are less effective.

Katherine:

What is a genetic mutation?

Dr. Wang:

A genetic mutation is a mutation that occurs in the RNA of a cancer cell. That RNA dam – RNA aberration or abnormality does lead to different RNA – what we call transcript levels that lead to abnormal proteins.

Those proteins function in the cells to make a cell a cancer cell, okay? So, all cancer cells start out as normal cells, and as they acquire a mutation, they become a little less normal, and they start acquiring multiple mutations, and some of these mutations occur without DNA changes, some of them occur with DNA changes. And as these abnormalities occur, the cell gets more and more dysfunctional, and eventually, it starts becoming almost evil-ish.

It starts acquiring behaviors that are not normal, and then it starts to grow out of control, and that unchecked growth really is the end result of potentially many mutations occurring over time to drive that cell into becoming a cancer cell, and we call that process transformation, transforming from a normal, healthy-looking cell into almost a monstrous, cancer-like cell.

Katherine:

How do biomarkers affect AML treatment choices?

Dr. Wang:

So, those biomarkers, as I talked about, those mutations can determine what type of therapy patients can have. For example, up to 25 percent or 37 percent of newly diagnosed AML patients will have leukemia cells that carry the biomarker or the mutation in a gene called FLT3, or “flit.”

Those FLT3 cells can be inhibited by specific targeted therapies, including a drug called gilteritinib (Xospata), which is a pill which blocks mutant FLT3 expressed by AML cells. So, we’ve demonstrated, actually, in a randomized clinical trial that patients who have relapsed or recurrent AML who carry cells that have that biomarker – that FLT3 mutation – will actually do better if they take a daily pill – a FLT3 inhibitor – every single day for treatment of their aggressive acute myeloid leukemia than if we gave them low- or even high-dose chemotherapy in the hospital for four to six weeks.

So, that’s the power of those targeted therapies. Because the biomarker is telling you that there’s a sensitivity of that cancer cell to a specific blockage of that pathway, that can really dramatically change the course.

That is where the importance and the power of those biomarkers really goes into play. In the past, patients who had acute myeloid leukemia with FLT3 mutations did poorly with chemotherapy and had disease that came back even after multiple rounds of that intensive chemotherapy. The fact that we can give a pill and people could do better or even go to a bone marrow transplant off treatment with the pill is pretty remarkable.

Which AML Treatment Is Right for You? What You Need to Know

Which AML Treatment Is Right for You? What You Need to Know from Patient Empowerment Network on Vimeo.

What should you know before deciding which treatment is best for YOUR AML? AML specialist Dr. Ellen Ritchie reviews key factors that guide treatment choices, including biomarker testing results, and shares advice for partnering with your team to advocate for the best care.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here: weillcornell.org/ekritchie.

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Expert Advice for AML Patients When Making Treatment Choices

Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss how to access the most personalized AML therapy for your individual disease, and why it’s essential to insist on key testing. Before we meet our guest, 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 information to follow along during this webinar. 

Finally, 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. All right, let’s meet our guest today. Joining me is Dr. Ellen Ritchie. Dr. Ritchie, would you please introduce yourself? 

Dr. Ritchie:

Hello, my name is Dr. Ellen Ritchie, and I am an attending with a Leukemia service, and an assistant director since, for the last 15 years. 

And I treat mainly Acute Myeloid Leukemia, Myelodysplastic syndromes, which are kind of a pre-Leukemia; and Myeloproliferative diseases. And have a particular interest in the treatment of older patients with AML.  

Katherine:

Excellent, well thank you so much for joining us today. As we begin to talk about personalized therapy and AML, let’s start with the basics. How would you define personalized medicine? 

Dr. Ritchie:

Personalized medicine, to me is really, it’s a difficult question. It’s trying to find the best treatment for a particular patient. And it’s looking at biologic issues, what kind of cancer, what type of AML is it, what are the specific mutations or chromosomal abnormalities. But it’s also looking at the person. Is the patient active or not active? Do they have lots of other diseases like diabetes and coronary artery disease? Or pulmonary disease, or are they completely healthy? 

Or, do they have support at home? If they’re sick at home is there someone who can take care of them, versus a situation where you’re older and alone and you have no real family member to rely on. So, all of these things are very important in making a personalized decision as to how you treat a patient. 

Katherine:

Well, it sounds like, each person’s AML is unique. So, let’s help our audience be clear about basic testing. What tests are necessary to help understand a patient’s specific disease at diagnosis? 

 Dr. Ritchie:

I mean certainly it’s important to do a physical exam and to find out what the general health of the patient is. In order to evaluate an AML, or any other Leukemia, I look at the peripheral blood smear. To look at what I think the type of Leukemia might be that I am dealing with. There are some Leukemias that have particular way that they look like Acute Promyelocytic Leukemia for which there is a designated therapy which works.  

And you can tell that just by looking at a peripheral blood slide. The next test is always a bone marrow biopsy. Patients are not delighted that that is a test, but it is a test that can be done in the office, usually within 15 to 20 minutes. And that test gives us a lot of information. It gives us information about what type of AML it is, what are the markers on the outside of the cell, it gives us information about the chromosomes inside the Leukemia cell. Are there missing chromosomes, or rearranged chromosomes? And if there are, that can be very relevant to the prognosis. And lastly, it’s sent for a particular mutations or markers. So, we look for IDH3 mutations, we look for FLT3 mutations, we look for IDH1 and IDH2 mutations, and we do an entire myeloid panel. Which is about 44/45 genes that are most commonly mutated in patients with AML.  

So that’s the initial work up for any AML patient. 

Katherine:

You mentioned markers Dr. Ritchie. What is genomic, or bio marker testing? 

Dr. Ritchie:

So, we’re looking really at most specifically at mutations inside individual genes that might be in your Leukemia cell. So, there are some mutations actually that confer a better prognosis. Like NPM1 or CEPBA, those can be more positive type of prognosis than some of the others.  

But we’re also looking for markers that might be targetable with certain therapies that we have. So, if you have a FLT3 ITD or TKD, we actually have particular drugs which can target those particular mutations. There are also drugs that are FDA approved to treat IDH1 and IDH2 mutations. 

There are certain mutations that have a relatively poor prognosis, like TP53 for which there are clinical trials which are available, which specifically are meant to target patients who have those sorts of mutations. And there’re other clinical trials using the FDA approved drugs that I just mentioned, for FLT3, for IDH1 and IDH2 and combining it with other agents to try and improve outcome in AML patients. 

Katherine:

Some patients may not know if they’ve received these important tests, so what key questions should they be asking their physician about testing? 

Dr. Ritchie:

So, physicians, they – financial coverage of the mutational testing is not uniform across the country and across insurances. So, Medicare and different Medicare insurances and some of the private insurances all vary in their coverage.  

So, in my clinic, I am asking – I prefer the test that we do in house at Cornell. But it’s important that I ask, what will their insurance cover. And make sure that I send the appropriate testing that will be covered by insurance. There are some insurances that will not cover this type of testing. So, it is a real question for the patient, when you go to see the doctor to say, are you going to do mutational NGS testing?  

And, will my insurance cover this? Hopefully most – if Medicare adopts the coverage of these types of mutational testing, it’s often true that private insurance will eventually pick this up. But it’s a murky field and it’s really important to talk to your doctor about this. The cost of the bone marrow biopsy, and the chromosomal evaluation is nearly always covered by insurance.  

Katherine:

Okay, that’s really great advice, thank you. How do the results of these tests affect prognosis and treatment? 

Dr. Ritchie:

Well, when a patient has AML, if they are a fit patient, if it will help us determine after initial induction, whether to cure the patient we need to do a bone marrow transplant, or we can just continue with chemotherapy.  

And those are really important things to determine. So, if you have a good prognosis AML, if you have an AML that has certain translocations like inversion 16 or 821, or if you have a CEPBA mutation or you have an NPM1 mutation, and that’s all you have, you may do particularly well with chemotherapy treatment alone. And you won’t need to have a bone marrow transplant. 

If you have certain other mutations, we know that the only way that we’re going to cure you, is with a bone marrow transplant. And if you are fit, when we finish induction and even as we’re doing induction, we’re preparing you for a bone marrow transplant down the line.  

One disadvantage, just to mention about the molecular testing, is it doesn’t come back as quickly as some of the other testing. So that you will have already started induction chemotherapy most generally before the mutational testing comes back. Which can be anywhere – depending upon the institution, between seven and 21 days. So, it takes time for those results to be available.  

Katherine:

Outside of test results Dr. Ritchie, what other factors should be considered when choosing treatment? 

Dr. Ritchie:

So, you want to choose whether a patient is most likely to benefit from intense induction chemotherapy. With strong chemotherapies where the backbone of those therapies would be an anthracycline, like Daunorubicin or Cytarabine, or Daunorubicin or Idarubicin, together with Cytarabine. And these are intensive chemotherapies. Versus, non-intensive chemotherapy which is able to be done as an outpatient, more frequently. And it is something that is gentler for a patient, they’re less likely to have severe toxicity. And the backbone of those regimens is using a drug called Azacitidine or Decitabine, together with a second drug called Venetoclax. 

So, these are the two backbones, there may be clinical trials or there may be targetable aspects of your Leukemia, which drugs would be added to either of those backbones. But those are the two backbones. And I also like to identify those patients that may not benefit from chemotherapy at all. And so, it’s very important, I think to really get to know your patient. And I spend time with my patient, particularly on the first visit, to understand not only their physical health, but their mental health. How good is their cognition, what is their mood, are they depressed, or are they happy people? And what is their circumstance? Do they have people to support them? Do they live close to family? Is a caregiver able to come, with an elderly patient for example, to visits? 

Those, and whether or not they’re living alone and need tremendous support. So that’s really important to determine and helps me to choose what the best therapy might be. And also, concurrently what I can do to shore up the patient to do better with whatever therapy that I’m giving them. I.E., if you’re depressed, let’s work on that, or if your blood pressure is too high, or if you are – your diabetes is out of control at the same time that I’m seeing you, to try and fix those particular problems. In older patients I often do sort of a miniature version of the geriatric assessment. And in trials that have been so far, the most important aspects of the geriatric assessment, are really what is your cognitive function? Do have a mild dementia or do you not have a mild dementia? Because dementia may be or mild dementia may be associated with poorer outcome. 

The other is, are you able to do what we call the incidental tasks of daily life. So, you know fundamental tasks are really brushing your teeth and combing your hair, and dressing yourself. But are you able to do your cooking and your shopping and your banking and those things? Patients who have trouble doing their cooking and shopping and banking, and those types of activities, that also has been associated with a poor overall survival in AML. So, it’s really important to determine all of those aspects and if there are any deficiencies, to really know that the only therapeutic choice for that particular patient would be a low-intensity therapy. 

Katherine:

You touched upon this earlier, but what targeted therapies or treatments are available for AML patients? 

Dr. Ritchie:

So, there have been many recent FDA approvals of drugs that are targeted. One, is the FLT3 inhibitors. And the two that are available are Midostaurin, which is most commonly – was the first drug that was really added to intensive chemotherapy. 

And clinical trials show that in those FLT3 positive population that patients had an overall better outcome if Midostaurin were added to intensive chemotherapy. There’s also a drug called gilteritinib, and this drug is also a FLT3 inhibitor that was tested in patients who had refractory leukemia. They could either get real chemotherapy regimen or they could get gilteritinib. And it turns out in the FLT3-positive patients, the gilteritinib was superior to the strong chemotherapy. So that’s been approved for patients who have refractory, or disease that didn’t really respond to initial therapy, that is IDH – or is FLT3 positive.  

Then there’s the IDH1 and IDH2 inhibitors that have also been approved, and a small proportion of AML patients will be positive for IDH1 or IDH2 mutations. 

The IDH1 inhibitor Ivosidenib, is available and can be used to treat patients if you know up front, they have an IDH1 inhibitor. So, that’s a regimen where the single agent can be used to treat an IDH1 mutated patient who’s newly diagnosed. Those patients are also eligible for many clinical trials now, where they’re combining that particular drug with other agents, in an effort to improve outcome. For IDH2 positive patients, there’s a drug called Enasidenib. And this drug is used mainly in patients in the second line setting. But it specifically targets IDH2. And patients go into remission sometimes for a prolonged period of time. So, these drugs are FDA approved, and they’re treating targetable mutations.  

TP53 mutations are a particularly bothersome mutation because it confers a poor outcome. And I’m happy to say that we have clinical trials now that are available that actually target TP53 mutations.  

So, there are – there is therapy available for that type of mutation that was not available before through the clinical trials. And I expect in coming years that we’re gonna see more and more targeted therapies develop in AML which can be used potentially in combination with what we’re already using as backbones to enhance the outcome of patients with this disease. 

Katherine:

Well, how do targeted therapies work? 

Dr. Ritchie:

So, targeted therapies work on – it’s sort of complicated. The targets which are available, IDH or the FLT3 is really on the outside of the cell and it is a drug which is targeted directly to the FLT3 on the outside of the cell. 

It works quite well in the peripheral blood, where you see the blast oftentimes disappear. The big concern always is how well it’s working getting deep into the marrow. But it’s looking at the target on the outside of the cell. IDH1 and IDH2 inhibitors work on particular chemicals which are involved in the kreb cycle, and those of you that took high school chemistry may have memories buried in the deep parts of your brain of learning the kreb cycle. And this is a fundamental metabolic cycle inside cells, and if you have a mutation, an IDH1 or IDH2, you’re unable to go through that full kreb cycle in the appropriate way. And that is something that leads to you having a cancer, in this case AML. So, these drugs actually interfere with what’s happening in that kreb cycle, and allow you to make more normal cells. 

Katherine:

You mentioned earlier Dr. Ritchie, low-intensity therapy. Could you tell us about the types of treatment options? 

Dr. Ritchie:

So, I’ll go – high-intensity therapy or intense chemotherapy always has to be given really in a hospital. And if you don’t start it – if you can start certain intensive chemotherapies, like Vyxeos, which is also intensive, in the outpatient setting, but by day seven or eight, you end up in the hospital. And in intensive chemotherapies, you lose your hair, there’s GI toxicities, you’re at high risk of developing infections and you need a lot of transfusion. And for even young people, it’s a difficult therapy for which you’re in the hospital, and 90-some percent of patients are on IV antibiotics. 

So, it’s intensive chemotherapy because it has to be given in a hospital setting and requires intensive supportive care. Low-intensity therapy can be given in the outpatient setting. So, at the present time you can get a drug like Azacitidine, for example, which is an injection that you get seven days in a row. Unfortunately, you have to come to the doctor’s office every day for those injections, but once you’ve had the injection, you can go home. Combined with Venetoclax which is an oral agent. So, an oral agent can be given at home. You need close supervision in the physician’s office when you’re on this type of therapy, but you don’t need the constant support that you need if you are getting intensive chemotherapy. So, it can be done, in the comfort really of your home and with your family. You will have to come in and have transfusions potentially as an outpatient, nearly everyone does. And there’s always the risk that you develop a fever and if you do, you have to come into the hospital for IV antibiotics. 

But in general, low-intensity means not so much support needed in a hospitalized setting, and the tolerability of this particular chemotherapy in the outpatient setting.  

Katherine:

Once a patient has begun treatment, how do you monitor whether it’s working? 

Dr. Ritchie:

So, one of the more frustrating things about being an AML patient, is you don’t know right off the bat whether or not that you have gone into remission. So, what happens is you receive the chemotherapy, and the day you start chemotherapy is really day one. And somewhere around day 14, you’re at your lowest point. So, your blood counts are low, and you often feel really terrible, and you really wonder, is this working? But unfortunately, I can’t really tell you. Some institutions do bone marrow biopsies if you have intensive chemotherapy on day 14, or if you’re getting Venetoclax therapy somewhere around day 21 to look and see whether they still see Leukemia cells, but the utility of that is different per institution.  

The real test of whether chemotherapy x`, is at the end of about 28-35 days, are your blood counts coming up, and are you making normal blood cells. Are you making platelets, which are the part of the blood that clots the blood? Or are you making neutrophils, which are the important cells needed to help you fight infection. So, the real proof of a remission, is are your platelets over 100,000? Is your neutrophil count over 1,000? And when we look in the bone marrow around that time, do we see normal cells developing and no Leukemia? 

Katherine:

How often should testing take place? And should patients be retested over time? 

Dr. Ritchie:

So, the bone marrow biopsy is done frequently once you have a diagnosis of Acute Leukemia. So certainly, it’s done upon diagnosis of the disease. 

And as I mentioned earlier in certain institutions, about halfway through your chemotherapy cycle, they’ll do a bone marrow biopsy to see whether or not they see any residual Leukemia cells. That’s not done everywhere, and it’s done differently depending upon institutions sometimes. At the end of the chemotherapy treatment, if you recover your blood counts, we do a bone marrow biopsy to confirm a remission. If by day 35, we haven’t seen that your blood counts are recovering, we may do a bone marrow biopsy to see whether or not we see Leukemia cells in there, or early recovery. So, you’re definitely going to have bone marrows at those time points. If you’ve gone into remission, it depends on what we’d do next as to when you would have another bone marrow biopsy. So, if you’re going to bone marrow transplant you may have one more biopsy, just prior to going into transplant, and another biopsy at the end of the first month after transplant. 

If you’re gonna have what we call ongoing therapy, roughly every three or four months, we may do a bone marrow biopsy to determine whether or not the remission is holding. If during ongoing therapy, we see that there is blood count abnormalities that we weren’t expecting, that might be a reason that we would do a bone marrow biopsy. And that’s unpredictable as to when that would be.  

Katherine:

Dr. Ritchie, what advice do you have for patients to help them feel more confident in speaking up and advocating, being a partner in their care? 

Dr. Ritchie:

Well, when you choose a Leukemia doctor, you need to choose someone that you can actually communicate with. Someone who you feel is not allowing you to ask questions, or is not curious about what your life is like, you may wanna think, I wanna check out somebody else.  

Because it’s really important you like the person who’s your doctor, and that you have a trust relationship together. So, it’s really – I tell some patients it’s a marriage of convenience that we have. And that you really have to think of it that way. If someone doesn’t allow you to ask questions or if they are not fully answering your questions in a way that you understand, try and speak up for yourself and make sure that the doctor tries to address that. And if the doctor won’t address those things for you, or you feel like you don’t understand what is being explained to you, then you can think about trying to see someone else. I think it’s really important if you can, to write down as many questions as you have about your disease before you come in. 

Because often what happens is you get there, you’re stunned by the amount of information, and the questions you wanted to ask, you forget. And the next day, you’re like, ugh, I didn’t ask these questions. So, before you come in, if you write questions. Questions about insurance coverage, that may not be something that we go over. Or questions about toxicities, or questions, if I’m gonna lose my hair, do you have the name of a wig facility. All these questions that you might have, put them on a piece of paper, so that they can be addressed when you’re with the doctor. And other things will come up, you’ll have other questions when you’re there, but make sure your fundamental questions are answered. 

Katherine:

Yeah, those are great suggestions. We have a couple of audience questions. Mike wants to know, what does it mean to have high-risk AML? 

Dr. Ritchie:

High-risk AML means that there is something in your chromosomes that are worrisome and may confer a worse outcome. Or that one of the mutations that you have, or the combination of mutations that you have and the genetic testing are poor risk mutations that are associated with poor outcome. So, high-risk, really means a high risk of progression, or a high risk of – it’s a high risk of not going into remission and not being treatable AML. So, these are AMLs we treat aggressively, and if we get a patient into remission, we generally send high-risk patients to a bone marrow transplant. 

Katherine:

The second question is from Craig, he says; I’m currently undergoing treatment for AML, is the Covid-19 vaccine safe and effective? 

Dr. Ritchie:

I recommend the Covid-19 vaccine to everyone, all my patients. A little immunity is better than none. And there is preliminary data, looking at patients with Myeloid malignancies, not Lymphoid, but Myeloid malignancies, where it appears there is an immune response to the Covid-19 vaccine. So, I would suggest that you get the Covid-19 vaccine. Any of them that are available, are good. Whether it’s Moderna, or Pfizer, or Johnson and Johnson. Whatever is available to you, you should go ahead and get. 

Katherine:

Are there any symptoms or issues that AML patients should be looking for post-vaccine? 

Dr. Ritchie:

Post-vaccine, there’s a lot of symptoms that people have. And they can be similar among Myeloid patients. Some of my patients have had no reaction whatsoever, some people have had a really sore arm. 

Some patients are incredibly tired after the vaccine; some patients develop a low-grade fever for a couple of days. Those are really what we watch for. Sometimes when there’s a reaction, we’re hopeful that there’s an antibody being made, or an immune response that’s developing. So, it’s not always a bad thing if you have a reaction. But I don’t think that the reactions of patients of Myeloid malignancies is any different than that of the general public. 

Katherine:

That’s what it sounds like. To close Dr. Ritchie, what would you like to leave the audience with? Are you hopeful about the future of AML treatment? 

Dr. Ritchie:

I’m very hopeful. I’ve worked in this field for 15 years and through the 15 years we have seen a lot of new drugs that have been approved for AML. It’s remarkable, the FLT3 inhibitors, IDH1 and IDH2 inhibitors, new formulations of intensive chemotherapy, like Vyxeos, the Pfizer drug; glasdegib – I can never say that one. And most importantly, venetoclax, which has really revolutionized our treatment of low-risk, or not low-risk, but the low intensity patient. 

I see in the future that there is gonna be more – there’s an emphasis on immunotherapy, so I think we’re gonna see more antibody-based therapy that’s going to be approved by the FDA. Maybe it will be used in combination with the drugs that we are already using. There are all sorts of combinations using all the FDA approved drugs in different ways together. So, we can maybe do better with the drugs that we have. And there’s always new targeted drugs which are being tested in AML. So, I think as time goes on, from a molecular perspective it will be even more targeted. And I’m hoping also that there will be oral formulations of a lot of our drugs. So, it’s kind of exciting that there’s an oral form of Decitabine called Inqovi, which is something that could potentially be given in induction therapy right off the bat with Venetoclax for an all-oral regimen at home. 

All of these things are great advances, in my opinion, and I think that the opportunity to treat patients outside the hospital, with more targeted therapy and immunotherapy is gonna be the future. 

Katherine:

Yeah. And the future sounds promising. Thank you so much for joining us today Dr. Ritchie. 

Dr. Ritchie:

Thank you for having me. 

Katherine:

And thank you to all of our partners.  

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.

Treatment Approaches in AML: Key Testing for Personalized Care

When it comes to Acute Myeloid Leukemia (AML), genetic testing (or biomarker testing) is essential in helping to determine the best treatment approach for YOU. In this program, AML expert, Dr. Naval Daver reviews key decision-making factors, current AML treatments and emerging research for patients with AML.

About the Guest:
Dr. Naval Daver is an Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. More about Dr. Daver: https://faculty.mdanderson.org/profiles/naval_daver.html