Tag Archive for: Roswell Park Comprehensive Cancer Center

Advances in Non-Small Cell Lung Cancer Testing

Advances in Non-Small Cell Lung Cancer Testing from Patient Empowerment Network on Vimeo.

Lung cancer expert Dr. Grace Dy discusses the latest research in lung cancer testing, including liquid biopsies and minimal residual disease (MRD).

Dr. Grace Dy is Chief of Thoracic Oncology and Professor of Oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Grace Dy.

See More From INSIST! Lung Cancer

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An Expert Explains Predictive Biomarker Testing for Lung Cancer

An Expert Explains Predictive Biomarker Testing for Lung Cancer

The Role of Antibody Drug Conjugates in Lung Cancer Care

The Role of Antibody Drug Conjugates in Lung Cancer Care

What Biomarkers Affect Lung Cancer Care and Treatment

What Biomarkers Affect Lung Cancer Care and Treatment?


Transcript:

Katherine Banwell:

As we know, researchers are still discovering new markers. Could you tell us about the latest news and research in biomarker testing for non-small cell lung cancer? 

Dr. Grace Dy:

Oh, there is a lot going on. You know, sky’s the limit. But just an example: we have liquid biopsies that are in clinical use right now, typically in the stage IV setting.  

But beyond that, we’re also having what we call minimal residual disease testing in what we call adjuvant situations. For example, patients who had surgery, there’s a big proportion of patients who still relapse.  

So, finding out – and our scans are imperfect. They will not be able to detect micro metastatic clones or even a small cluster.  

If you have a million cancer cells clustered somewhere, it will not show on the scan. 

Katherine Banwell:

Each and every one of them. 

Dr. Grace Dy:

Right. So, is there a better way? And so, that’s the question: can we detect it in the blood? So, these are assays that are being developed. Looking at different angles, not necessarily mutations, but maybe what we call epigenetic, meaning changes on top of the DNA that makes the DNA molecule be different in terms of whether some areas of the gene will be expressed or not. 

And so, looking at these patterns because they’re different in cancers versus non-cancers. So, whether you can see it in the blood. So, it’s a ripe area.  

There’s a lot of – so, there’s some overlap with early cancer detection and MRD, or minimal residual disease testing. 

So, I think there’s an intense interest in developing these. But none are fully validated yet. There are trials that are going on, the studies that are ongoing to prove the utility and validity of these tests. So, we’re very excited. And obviously, AI everywhere. You have ChatGPT, right? So, you have AI being incorporated in diagnostics as well, in radiology, in pathology, to see: hey, maybe can we use AI technology to even maybe one day give us a mutation profile, right?   

Katherine Banwell:

Yeah. 

Dr. Grace Dy:

And that would be huge, right? But we’re not there yet. 

The Role of Antibody Drug Conjugates in Lung Cancer Care

The Role of Antibody Drug Conjugates in Lung Cancer Care from Patient Empowerment Network on Vimeo.

What are antibody drug conjugates (ADCs)? Expert Dr. Grace Dy defines this new class of therapy and explains how ADCs work to treat lung cancer.

Dr. Grace Dy is Chief of Thoracic Oncology and Professor of Oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Grace Dy.

See More From INSIST! Lung Cancer

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Advances in Non-Small Cell Lung Cancer Testing

Advances in Non-Small Cell Lung Cancer Testing

Which Tests Do You Need Before Choosing a Lung Cancer Treatment?

How Can You Access Personalized Medicine for Non-Small Cell Lung Cancer?

How Can You Access Personalized Medicine for Non-Small Cell Lung Cancer? 


Transcript:

Katherine Banwell:

What is the role of antibody drug conjugates in lung cancer care? 

Dr. Grace Dy:

So, the antibody drug conjugates are an exciting new class of therapy. In fact, it’s been developed for decades, but we had the first antibody drug conjugate that was just approved less than a year ago in lung cancer. And that’s the drug called trastuzumab deruxtecan (Enhertu). It seems like we’re always steps behind our breast cancer colleagues. 

You know, trastuzumab deruxtecan was first developed in breast cancer patients. But hey, we also find we can have some subset of patients who will derive benefit from that. But that’s just one example. There’s plenty of antibody drug conjugates that are being developed. 

So, what are antibody drug conjugates? So, as the name implies, it’s an antibody that is attached to a drug that is actually typically chemotherapy, but you can use any other drug. Generally, it’s a chemotherapy. So, you can think of it as a targeted way of delivering chemotherapy because the antibody is very specific to a certain protein. And generally, what we try to do is look for proteins that are more expressed in cancers than in normal tissues. And you try to target that and improve the therapeutic index by using a more potent chemotherapy and potentially increase efficacy that way.

What Biomarkers Affect Lung Cancer Care and Treatment?

What Biomarkers Affect Lung Cancer Care and Treatment? from Patient Empowerment Network on Vimeo.

Lung cancer driver mutations can have an impact on therapy choices for patients. Dr. Grace Dy discusses the various lung cancer driver mutations and how treatment options may target specific markers.

Dr. Grace Dy is Chief of Thoracic Oncology and Professor of Oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Grace Dy.

See More From INSIST! Lung Cancer

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An Expert Explains Predictive Biomarker Testing for Lung Cancer

An Expert Explains Predictive Biomarker Testing for Lung Cancer

How Does Biomarker Testing Impact Non-Small Cell Lung Cancer Care?

How Does Biomarker Testing Impact Non-Small Cell Lung Cancer Care?

Why Do Lung Cancer Patients Need Molecular Testing Before Choosing Treatment?

Why Do Lung Cancer Patients Need Molecular Testing Before Choosing Treatment?


Transcript:

Katherine Banwell:

How does testing impact treatment and care? 

Dr. Grace Dy:

So, back in like maybe more than two decades ago, I was still in school. The treatment paradigm is sort of like a one size fits all. You come in with a lung cancer diagnosis. Everybody gets treated the same.  

But with advancements in technology and understanding of actually what we call lung cancer is really genetically very different from one patient to another. We are actually not even still able to tease out all the particular details, but there are some improvements that have been made along the way. And so, defining, for example, mutations in cancers, there are what we call driver mutations that have a matched targeted therapy.  

In certain patients, actually the target therapy works so much better than chemotherapy, for example. And that’s why we have it in guidelines based on the results of clinical trials showing that in the appropriate setting, if you have a mutation that we discovered through molecular testing, and then you use the matched target therapy, survival is so much better compared to, for example, chemotherapy.  

Same with immunotherapy. If we use a biomarker to test out which patients may actually respond well to immunotherapy alone – so, that’s a major treatment paradigm change within the less than 10 years wherein we define there’s a group of patients where that’s all they need. Non-chemo, just immunotherapy, and they will do well. 

Katherine Banwell:

What are some of the mutations that are being targeted? 

Dr. Grace Dy:

Right. So, it seems like every year, it’s growing. So, it started off with the poster child in lung cancer story of EGFR. So, we have EGFR mutations. Even EGFR mutations, they’re a subtype of mutations for – there are certain drugs that work better for certain mutations.  

So, we have the classical EGFR mutations, the atypical EGFR mutations. But EGFR mutations as a group are probably the most characterized given the longevity of the research that has been done. But there’s a lot more. 

So, for example, ALK, KRAS, BRAF, HER2, NTFK, NRG, RET, MET. Even those mutations, they’re all these new ones. It’s between the subtype of mutations. For example, we talked about EGFR. Same thing with MET. You have MET exon 14 skip mutations. But in the absence of MET skip mutations, there are also what we call MET gene amplification, MET protein over-expression that have matching therapies that may actually work better. 

But we’re still kind of scratching the surface. There’s a whole lot more being characterized and developed. Case in point, just a little over a year ago, there’s an LTK Fusion that was described. Very rare. But there’s a target therapy for it. So, unless you test it, you won’t find a matching targeted therapy. 

An Expert Explains Predictive Biomarker Testing for Lung Cancer

An Expert Explains Predictive Biomarker Testing for Lung Cancer from Patient Empowerment Network on Vimeo.

What is lung cancer biomarker testing? Dr. Grace Dy defines both biomarker and molecular testing and explains how these test results are used in lung cancer patient care.

Dr. Grace Dy is Chief of Thoracic Oncology and Professor of Oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Grace Dy.

See More From INSIST! Lung Cancer

Related Resources:

What Biomarkers Affect Lung Cancer Care and Treatment

What Biomarkers Affect Lung Cancer Care and Treatment?

The Role of Antibody Drug Conjugates in Lung Cancer Care

The Role of Antibody Drug Conjugates in Lung Cancer Care

Advances in Non-Small Cell Lung Cancer Testing

Advances in Non-Small Cell Lung Cancer Testing


Transcript:

Dr. Grace Dy:

My name is Grace Dy. I’m a thoracic medical oncologist at Roswell Park Comprehensive Cancer Center here in Buffalo, New York. 

Katherine Banwell:

Thank you for being with us today.  

Dr. Grace Dy:

Thank you for having me. 

Katherine Banwell:

What is biomarker testing, and is this the same as molecular testing for non-small cell lung cancer? 

Dr. Grace Dy:

That’s a very good question. So, let’s first maybe define what biomarker means. So, biomarker is an all-encompassing term relating to a measurement of a biological parameter. That’s what it means.  

So, you can actually have biomarker related to imaging. So, it’s not specific to a particular test. But what it’s trying to do is to guide doctors in making decisions. So, you can have, for example, a PET scan as a biomarker to indicate the effectiveness of therapy. 

So, it’s not specific to a test. So, it’s a broader scope. But in cancer, generally, it’s used interchangeably with molecular testing. And molecular testing is a more focused test on the genetics of the cancer.  

In some aspects, sometimes it also refers to testing for proteins, characteristics of different proteins in the cancer. Again, to help doctors generally define what might be a better treatment option that is personalized to the patient’s cancer. 

In some instances, the biomarker can also be what we call prognostic, meaning independent of what we do with the treatment, it may define to us how well a patient will survive or have their outcomes, whether they have treatment or not. 

So, those are maybe the nuances between a predictive versus a prognostic biomarker. But for all intents and purposes, the most common test that we use for lung cancer patients are what we call predictive biomarker testing. Molecular testing is one of the ones that we often commonly request to help us define treatment modalities, especially in non-small cell lung cancer. 

What Procedures Are in Place to Protect Lung Cancer Clinical Trial Participants?

What Procedures Are in Place to Protect Lung Cancer Clinical Trial Participants? from Patient Empowerment Network on Vimeo.

What safety measures are in place to protect people in lung cancer clinical trials? Dr. Grace Dy reviews protocols to help maintain clinical trial safety.

Dr. Grace Dy is Chief of Thoracic Oncology and Professor of Oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Grace Dy.

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Transcript:

Katherine Banwell:

What safety measures are in place to safeguard patients?  

Dr. Grace Dy:

So, there’s a lot of safety measures involved. Not just within the protocol but there are also governing committees. IRB, Scientific Review committees, that look over – and these committees typically also, actually, involve some patient advocates that will be reviewing the protocols to make sure it’s not just a scientific aspect that is looked into but also patient perspectives that are looked into when we review these protocols.  

So, from the medical perspective, protocols are generally written with guidelines to help treating doctors how to manage side effects. For example, because of the intense preparation – what we call pre-clinical, meaning the preparation done in animal models, in learning from other settings, for example; from other drugs, for example. If it’s not the first in class, you have a sense of what potential side-effects might be expected and so you prepare accordingly. 

Lung Cancer Clinical Trials | Addressing Common Patient Concerns

Lung Cancer Clinical Trials | Addressing Common Patient Concerns from Patient Empowerment Network on Vimeo.

Considering a lung cancer clinical trial can feel overwhelming and brings up a number of questions. Dr. Grace Dy reviews common concerns from patients, and explains how and when placebo may be used in trials.

Dr. Grace Dy is Chief of Thoracic Oncology and Professor of Oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Grace Dy.

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What Procedures Are in Place to Protect Lung Cancer Clinical Trial Participants

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Transcript:

Katherine Banwell:

What are some common concerns you hear from patients when discussing lung cancer clinical trial options?  

Dr. Grace Dy:

When I discuss clinical trials, the first question generally patients ask is: well, how effective is the drug, right? And the second question will be: well, what are the side effects? And those are very valid questions, but we may not always have an answer to it, especially if they’re in early phase. I do a lot of early phase clinical trials, meaning sometimes we don’t even know the proper dose of the drug to use, for example.  

And the intent of the trial, for example, in Phase I, generally, is to find out what is a proper dose to use that is safe and effective before we can do a test in Phase II setting using the recommended dose to test it out more rigorously how well it works. And if it passes Phase II, then we go to Phase III, which then generally is comparing it with the standard to see whether it will be better or at least equivalent or non-inferior. 

And you may ask, “Well, why even do a non-inferior?” Because, well, some drugs, it may not prolong your life more than current therapies, but if it has better side effect profile, right? So, there are actually drugs that are approved through non-inferiority trials. But those are the common concerns, and I think another common concern that I hear when I talk about trials, patients are concerned about receiving placebo. 

Katherine Banwell:

And what do you tell patients? 

Dr. Grace Dy:

Well, it depends on the design of the trial and the question that is being answered. So, in fact, for example, some situations in the standard of care is not to do anything. The best way to remove bias is to administer a placebo because the standard care would be not to do anything. And those, generally, are Phase III, you know. An early phase, Phase I, Phase II generally there are no placebo involved. I mean, there are some randomized Phase II trials that there are placebo involved and I explain to the patient why placebo may be involved and it’s usually on top of a standard of care. So, there could be a standard of care therapy but you add something else. So, you want to compare it with a new drug plus the standard of care. So, you might add placebo so that the doctors will not be bias when they measured their scans, for example. They say oh, this patient is getting this experimental drug. So, they’re excited. They might oh, you know, make it look better than what it actually is.  

Katherine Banwell:

Now, as a researcher yourself, do you always know that a placebo is part of the clinical trial testing?  

Dr. Grace Dy:

Yes, it will be in the design. So, it will say there is a placebo control. So, the title, or the design, generally will tell you this is a randomized, double-blind placebo control. Usually if there is a blinded there might be some placebo involved because then you don’t know what people are getting.

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.