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What Are the Goals of Lung Cancer Treatment?

What Are the Goals of Lung Cancer Treatment? from Patient Empowerment Network on Vimeo.

The goals of lung cancer treatment can vary depending on the stage. Expert Dr. Heather Wakelee explains how lung cancer stage is determined and shares insight about the goals of treatment at each stage.

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.

See More From INSIST! Lung Cancer

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Accessing Personalized Treatment for Lung Cancer

Lung Cancer Treatment Decisions What Should Be Considered

Lung Cancer Treatment Decisions: What Should Be Considered?

In-Depth Testing for Lung Cancer Prognosis and Treatment

In-Depth Testing for Lung Cancer Prognosis and Treatment


Transcript:

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 gotta 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. 

In-Depth Testing for Lung Cancer Prognosis and Treatment

In-Depth Testing for Lung Cancer Prognosis and Treatment from Patient Empowerment Network on Vimeo.

How is in-depth lung cancer testing used in determining lung cancer prognosis and treatment? Expert Dr. Heather Wakelee shares insight about biomarker testing, genomic testing, and how test results may impact treatment options.

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.

See More From INSIST! Lung Cancer

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How Are Targeted Therapy and Immunotherapy Used in Lung Cancer Care?

Transcript:

Katherine:

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.

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. 

Which Tests Do You Need Following a Lung Cancer Diagnosis?

Which Tests Do You Need Following a Lung Cancer Diagnosis? from Patient Empowerment Network on Vimeo.

Which lung cancer tests do patients need after a diagnosis? Expert Dr. Heather Wakelee provides an overview of lung cancer testing, explains how the results are used, and discusses how testing differs for small cell lung cancer versus non-small cell lung cancer.

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.

See More From INSIST! Lung Cancer

Related Resources:

Accessing Personalized Treatment for Lung Cancer

In-Depth Testing for Lung Cancer Prognosis and Treatment

In-Depth Testing for Lung Cancer Prognosis and Treatment


Transcript:

Katherine:

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 cannot 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 these 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. 

Accessing Personalized Treatment for Lung Cancer

 

Accessing Personalized Treatment for Lung Cancer from Patient Empowerment Network on Vimeo.

Lung cancer expert Dr. Heather Wakelee defines personalized medicine and explains the factors that are considered when determining a treatment approach.

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.

See More From INSIST! Lung Cancer

Related Programs:

 

Which Tests Do You Need Following a Lung Cancer Diagnosis?

In-Depth Testing for Lung Cancer Prognosis and Treatment

In-Depth Testing for Lung Cancer Prognosis and Treatment

Transcript:

Katherine:

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. 

Patient Considerations That Impact MPN Treatment Decisions

Patient Considerations That Impact MPN Treatment Decisions from Patient Empowerment Network on Vimeo.

How can personal choices play a role in your MPN care? Dr. John Mascarenhas reviews factors that should be considered, including lifestyle and overall health, when choosing therapy for essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF).

Dr. John Mascarenhas is Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai. Learn more about Dr. Mascarenhas, here.

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Transcript

Katherine Banwell:

Outside of testing, what other factors should be considered when choosing treatment?

Dr. Mascarenhas:       

I think patient expectation. So, sometimes physicians and family will impose what they want for a patient, and that may not be what the patient really wants. So, I have learned over the years that it’s crucial to make sure that you understand the patient and what the patient’s expectations, desires, and that’s influenced by the life they’ve lead or the remaining life that they want to live and their own personal religious and spiritual beliefs.

So, I think knowing your patient and understanding what their expectations are, it’s fundamental, and sometimes, it’s overlooked. So, understanding that, I think, is very crucial. And then, dividing what are the objectives of the treatment in a given patient? Is it really to improve anemia in some patient versus perhaps a different patient, it may be to improve their quality of life and reduce their symptom burden. And then in other patients, it may be purely trying to cure the disease with therapies that may be aggressive, which may not be appropriate for an older patient where toxicity could outweigh any potential benefit of survival or longevity. So, you really have to have a discussion with the patient or caregivers, and then define what are the goals in that individual to personalize that approach for that patient.

Katherine Banwell:                  

Right. Right. And, there’s the patient’s overall health, comorbidities, other things like that?

Dr. Mascarenhas:       

Yeah, because we are not treating a disease in isolation usually. So, patients come with baggage posed of past diseases, current diseases.

And sometimes patients are not “fit” for certain types of therapies because they may be sick or they may have organ dysfunction that would make certain types of treatment approaches ill-advised because the toxicity could be higher. So, absolutely, you need to know their comorbid index, how much comorbidities they have and also their performance status, how active and how well they are in general.

Katherine Banwell:                  

Are there specific biomarkers that may affect prognosis or treatment?

Dr. Mascarenhas:       

So, yes and no. I mean, I think that’s an area of intense interest and research. So, we have identified certain biomarkers that have, as I mentioned, prognostic significance, and that may influence treatment decisions. So, patients who have, for example, as we discussed next-generation sequencing and we see their mutations that are present, if they have an accumulation of high molecular risk mutations, that may give us a sense that perhaps that patient may not enjoy the full benefit and duration of benefit of, for example, a JAK inhibitor as another patient that has a less complex disease.

And, that doesn’t necessarily mean that the therapy is not appropriate for the patient. But it may help us plan and be prepared to move on to the next therapy sooner or to be more vigilant for changes that would tell us it’s time to move on. So, I think they help us maybe get a general sense of things and put things into perspective. They don’t always necessarily inform us on a change in therapy immediately or the next or the most immediate therapy. But I do think that that will change because I would predict in the next five to 10 years, I think that the number of available drugs for myelofibrosis, for example, will likely double from what it is now. I think we will have an armamentarium to choose from, and what we will learn from trials that are ongoing is there may be certain profiles, mutations, chromosomal profiles, other clinical variable profiles that we will learn from these trials that will help us to find upfront, “Well, this profile really should go with his medication. That profile should go with that medication.”

An early of example that would be we’re learning that not all patients with the JAK2 mutation are created equal, that you can have different burdens of JAK2 mutation.

And, patients with low burden JAK2 mutation, for example, may fare better with up a specific JAK to inhibitor like pacritinib than patients who get treated with other JAK inhibitors like ruxolitinib.

So, there are differences even within patient defined by mutation that may help us predict which of the JAK inhibitors, as an example, may be more appropriate as a first-line therapy. So, I think that will evolve more so over the next five to 10 years.

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.

See More From INSIST! Lung Cancer

Download Guide

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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 these 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.

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

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

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

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

See More From INSIST! Lung Cancer

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Transcript:

Katherine Banwell:

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

Dr. Preeshagul:

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

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

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

Katherine Banwell:

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

Dr. Preeshagul:

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

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

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

Katherine Banwell:

Are there specific biomarkers that affect lung cancer treatment choices?

Dr. Preeshagul:

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

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

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

What Key Tests Impact Lung Cancer Treatment Choices?

What Key Tests Impact Lung Cancer Treatment Choices? from Patient Empowerment Network on Vimeo.

Dr. Isabel Preeshagul, a lung cancer specialist, provides insight about lung cancer subtypes and how test results may play a role in determining the best treatment option for patients.

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

See More From INSIST! Lung Cancer

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Transcript:

Katherine Banwell:

When it comes to lung cancer, Dr. Preeshagul, what important tests should patients undergo that help in making treatment decisions?

Dr. Preeshagul:

So, it’s important to obviously confirm the diagnosis and make sure that it’s lung cancer, first of all. After that, you need to know the histologic subtypes. So, I mean, is this non-small cell, or is it small cell lung cancer?

And the difference between those two, it’s very important. They are not the same. Their treatments are different. Their prognosis is different. The staging is different. Everything is different. If you have non-small cell lung cancer, it’s important to know if you have adenocarcinoma or squamous cell carcinoma, large cell, neuroendocrine. It’s really important because the treatments vary. The prognosis varies. And how we approach those patients is different.

In addition to that, over the past 10 years, we have really come to understand the importance of next-generation sequencing testing, which I know we’re going to get to. But evaluating to see if your patient harbors any mutations or alterations that could be targetable because that would really change your treatment plan.

Katherine Banwell:

All right. So, let’s get to some of that testing. What is biomarker or molecular testing?

Dr. Preeshagul:

Sure. So, we use a lot of these terms synonymously. So, alteration, mutation, positive biomarkers, these are all basically one and the same. So, if you look at lung cancer 20 years ago, we really didn’t know about any of these. You had lung cancer, you got X, Y, and Z chemo. And that really was it.

But with the discovery of EGFR alterations and realizing that some patients harbor an EGFR mutation, and this mutation is what’s driving their tumor and then the discovery of erlotinib, or Tarceva, we realized that it’s important to evaluate for the presence of these mutations.

So, these are somatic mutations that occur within your tumor and drive your tumor to grow, and some of these alterations are targetable.

But some of these alterations that we find, unfortunately, and the majority of them, we don’t really know the significance of them as of yet, or we know the significance of them, but we don’t have a magic bean to treat them. But that does not mean that there won’t be something in the future.

Expert Perspective: Exciting Advances in Lung Cancer Treatment and Research

Expert Perspective: Exciting Advances in Lung Cancer Treatment and Research from Patient Empowerment Network on Vimeo.

What are the latest advances in lung cancer treatment and research? Dr. Isabel Preeshagul shares information about new treatment approvals, an update on targeted therapies, and new clinical trial approaches.

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

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Transcript:

Katherine Banwell:

Dr. Preeshagul, when it comes to lung cancer research and emerging treatment options, what specifically are you excited about? 

Dr. Preeshagul:

So, honestly, I feel that my interest and excitement are getting pulled in a million different directions as of now. Over the past 16 months, we’ve had 10 approvals in lung cancer, which is unheard of. 

Katherine Banwell:

Wow. 

Dr. Preeshagul:

It’s been a very, very, very busy time for us as thoracic oncologists, which is really exciting. 

I feel that we’ve really come to the forefront of cancer research, which is outstanding. In terms of what makes me excited, right now, I think it’s probably two things. There have been genetic alterations, somatic, that have really been almost like the orphan child in lung cancer. And we have unfortunately had to tell patients, “Listen, you have this KRAS G12C alteration. We know that it portents a poor prognosis. We know it’s more aggressive, but we don’t have anything for you that can target that.” 

And as of recently, within the past two months, we had this approval for a drug called sotorasib (Lumakras). This is based on the AMG 510 study. And it is a targeted therapy for patients with KRAS G12C, and the responses have been excellent. 

So, finally, we have something. So, it makes me feel good that when I have a patient that unfortunately has this alteration, I no longer have to give them the same song and dance, that I can talk about sotorasib and talk about it with confidence and talk to them about the data. And the same thing is true for patients with an EGFR exon 20 alteration with amivantamab that just got approved. So, it is now, I feel, that research is now unveiling these orphan alterations that we are now having targeted therapies for. 

So, that makes me excited. Also, something else that’s making me excited is the fact that we’re realizing and learning to anticipate these resistance alterations. So, we know if you have an EGFR mutation for say, we know now that, unfortunately, at some point, the treatments that we’re going to give you, this targeted therapy, this pill called osimertinib (Tagrisso) in the frontline setting, for some patients, unfortunately, at some point, it’s not going to work for you anymore. 

And this is because the cancer gets smart. It develops these resistance alterations. It knows how to usurp the osimertinib, and resist it, and make an alternate pathway, or change its form, turn into small cell, or come up with another alteration that makes the osimertinib not work. 

So, we’re realizing to look for these alterations earlier, faster than when a patient starts progressing, and anticipating them. So, our trials are now being designed in a way with combination therapy to figure out a way to outsmart this cancer. We always have to be one step ahead. And unfortunately, cancer is still many steps ahead of us. But we are learning to be smarter. 

Lung Cancer Treatment Decisions: What Should Be Considered?

Lung Cancer Treatment Decisions: What Should Be Considered? from Patient Empowerment Network on Vimeo.

What should be considered when making lung cancer treatment decisions? Dr. Isabel Preeshagul shares the factors that may affect treatment options, as well as how the patient can collaborate with their healthcare team for optimal care.

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

See More From Engage Lung Cancer

Related Resources:


Transcript:

 Katherine Banwell:

Dr. Preeshagul, let’s start with you introducing yourself, please.

Dr. Preeshagul:

So, my name’s Isabel Preeshagul. I’m a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, which is a large academic cancer center in the Northeast. And I’m part of a group of 24 thoracic oncologists.

I specialize in treating patients with non-small cell lung cancer, small cell lung cancer, mesothelioma, and some other thoracic malignancies but most really just focused on lung cancer. I have a very strong research interest in predictive markers for response to immunotherapy as well as targeted therapy.

Katherine Banwell:

Excellent. Thank you so much. What are the considerations when choosing a treatment for lung cancer?

Dr. Preeshagul:

So, that is a very weighted question. And I could talk about that for forever. But to try to be as succinct as possible, the most important thing is to really look at who you’re treating in front of you and try to treat the patient as a whole. It’s not only their diagnosis and their histologic subtype and their stage that’s important.

You really need to think about what’s important to the patient. Is someone a concert pianist or a violinist and giving them a treatment that could potentially cause neuropathy, could that be life altering for them? Or, are they of child-bearing age? What are their priorities?

So, that’s really important to me. Social aspects of a patient’s life, religious aspects, beliefs, ethical beliefs, all of that you need to take into consideration. And then getting more granular, you need to know about the tumor biology.

Do they have any driver alterations? Do they have any other predictive markers that may help you plan your treatment? So, it’s a lot of different things that go into treatment planning.

Katherine Banwell:

Just remind us what neuropathy is.

Dr. Preeshagul:

Sure. So, neuropathy is when the nerves that are in, I guess you could say, your fingers and toes start to damaged.

This can happen from diabetes, from having glucose that is too high for too long, or it can happen from certain chemotherapy agents that can affect the fine nerves in your fingers and toes and cause them to go numb. And this can really be painful. It can be life-altering. It can keep you up at night. It can make your sensation decrease.

So, if you’re walking on the floor, you may not feel a fine, little nail, or you may not even really feel the floor. And if you’re really focused on using your hands for playing the piano or violin or sewing or even any other kind of activity, it can really affect how well you’re able to perform.

Katherine Banwell:

Yeah. What is the role of the patient in making treatment decisions?

Dr. Preeshagul:

So, I think every doctor will give you a different answer for this. But for my practice, I really make sure that the patient is part of the team as well as family members, as long as the patient gives permission. I run everything by the patient, of course. I give them all the possible options ranging from ones that I think would be most efficacious to ones that I think are other options and of course, the option of no treatment, which is always an option, and sometimes, the best options.

So, I really say these are the things that we can offer you, but what do you feel most comfortable with? What’s important to you? And sometimes, patients are taken aback by this question because some patients like to be told, “Well, this is what we’re going do, and this is when we’re starting,” and X, Y, and Z. That’s not how I practice.

And it’s really important to me that the decisions come from the patient but are guided by me and my team.

Katherine Banwell:

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

Dr. Preeshagul:

So, that is such a good question. And I think a lot of it comes from the fact that you have a patient that had a completely normal life and all of a sudden get delivered this life-altering news that they have cancer. And everything that they had control over just seems to completely go out the window just in a matter of seconds.

So, making sure that a patient is back in the saddle and has control again and feels like they know what the next steps and feels like they know what they can expect is really important to them from what I can see. And I think that is something that allows them to feel like they’re a little bit more like themselves again.

They come to meet me. They don’t know anything about lung cancer. Their world has been completely rocked. And when they know their treatment plan and they know their stage and they know what to expect and they’re kind of a little bit more on autopilot, I can see in some patients them being able to exhale a little bit and feel like they’re in control again, and they know what – every Monday, I’m going to come and see Dr. Preeshagul. I’m going to get my treatment. I might not feel so good the next couple days, but I know the week after and the week after that, I might feel a little bit better. And they kind of are back in control again.

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

Which CLL 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 CLL? Dr. Lindsey Roeker discusses the role of key CLL tests, including biomarker testing, reviews emerging research, and provides tips for partnering with your care team to advocate for the best care. 

Download Guide

See More From INSIST! CLL


Related Resources

 

An Overview of CLL Treatment Types

What Should CLL Patients Know About Clinical Trial Treatment Options?

What Are the Goals of CLL Treatment?


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 CLL treatment 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 the webinar.

At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today, in order to help us plan future webinars. And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Joining me today is Dr. Lindsay Roeker. Dr. Roker, thank you so much for joining us. Would you introduce yourself?

Dr. Roeker:                 

Absolutely. So, my name is Lindsey Roeker, and I am a member of the CLL program at Memorial Sloan-Kettering Cancer Center in New York City.

Katherine:                  

Excellent, thank you. Let’s start at the beginning. How is CLL diagnosed?

Dr. Roeker:                 

Absolutely. So, for most patients, CLL is diagnosed after a routine blood test shows a high white blood cell count. That’s kinda the most common way that we find people entering into our clinic. Other things that people can notice is they have lumps or bumps that they’ve felt in their neck or under their armpits. Those are some other symptoms that can lead to the diagnosis, but often once a patient finds that their white blood cell count is high, some additional testing is done, and the diagnosis of CLL is made.

Katherine:                  

What are some common symptoms of CLL? You mentioned the lumps and bumps.

Dr. Roeker:                 

Yeah. So, often in early stages, the lumps and bumps in the neck are the most common that people recognize, but fevers or chills, night sweats, where patients are waking up drenched, having to change their pajamas, or weight loss without trying, are some other symptoms that can raise some alarm bells and make people start looking for something.

 And CLL can be a diagnosis that can be found through that, as well.

Katherine:                  

What is watch and wait?

Dr. Roeker:                 

So, after diagnosis, about two-thirds of patients enter this period of watch and wait, and what that means is we have good data to say that treating CLL before it’s causing symptoms doesn’t help people live better or live longer. And for that reason, we use the approach of watch and wait, and what that really means is you see your doctor a few times a year. I see people every three to four months. And you have your labs checked, have a physical exam, and through that process, just ensure that there are no symptoms that the CLL is causing that warrant therapy.

Katherine:                  

That’s very helpful. Thank you for that. Now, what tests are necessary to help understand a patient-specific disease, both at diagnosis and prior to treatment?

Dr. Roeker:                 

So, a diagnosis flow cytometry is the first test done, and what that means is, you take all of your white blood cells in your blood, and you run them through a fancy machine that puts them into buckets. So, you have a bucket of your normal neutrophils, a bucket of your normal lymphocytes, and then you find this bucket of cells that look somewhat unusual. And those have a specific look, if you will, and if they look like CLL cells, that’s how we make the diagnosis.

As you start reading, you’ll find that people talk about monoclonal B-cell lymphocytosis, which is MVL, CLL, and SLL, and a lot of times, it’s confusing because you start reading, and there are all of these – kind of lingo around it. So, what we’re looking for with flow cytometry is how many cells are in the peripheral blood? If it’s fewer than 5,000 per microliter – so, your doctor will talk to you; they’ll either say five or 5,000, depending on what units they’re using.

If it’s lower than that, and you don’t have any lumps or bumps or lymphadenopathy, meaning enlarged lymph nodes, that’s when we make the diagnosis of monoclonal B-cell lymphocytosis.

So, that’s kind of a pre-cancer diagnosis. Then, CLL, the diagnosis, is made in any patient who has greater than 5,000 cells per microliter, or five, if you’re using that unit, and that’s when the diagnosis of CLL is made. If people have lymph nodes that are enlarged, and there are CLL or SLL cells inside of them, but not a lot of involvement in the blood, that’s when we make the diagnosis of SLL, which is small lymphocytic lymphoma. So, CLL and SLL are really the same disease; it’s just where they manifest, primarily. So, whether it’s mostly in the blood, that’s CLL, or mostly in the lymph nodes, and that’s SLL.

Dr. Roeker:                 

Nope. So, that’s the flow cytometry test, and that’s kind of the test that leads to the diagnosis.

Katherine:                  

Got it. What about FISH and TP53 mutation?

Dr. Roeker:                 

So, at diagnosis, I often do this testing. Depending on which provider you go to, you may do it at diagnosis or closer to the time of needing treatment. But FISH is basically a test that looks for big changes in the chromosomes. So, if you remember back to high school biology and you see all of those chromosomes laid out, what FISH is looking for is big changes in those chromosomes. So, is there an entire arm of one of the chromosomes missing? And that’s what FISH does.

There’s also something called karyotyping, or in some institutions, they use something called SNP array. These are more refined tests that look for additional changes in the DNA. So, FISH is kind of a targeted look at a few different chromosomes, whereas karyotype or SNP array looks at all of the chromosomes. Then, there is TP53 mutational testing, and that is done through a bunch of different testing, often next-generation sequencing is what we use.

And we basically use a fancy spellcheck to see if there’s any misspellings, if you will, in TP53.

And TP53 is a gene that we use. It’s called the guardian of the genome. So, its job is basically to make sure that our cells are reproducing. They keep all the genes in working order. If TP53 is missing or misspelled, it doesn’t work as well, and that’s when people can get more issues with their CLL. It tends to be CLL that behaves a little more aggressively.

Katherine:                  

What about IGHV mutation status?

Dr. Roeker:                 

So, IGHV mutation status is a really important feature because it really is, of all of the things, what helps us understand the best way to go about therapy. And IGHV mutational status is basically a signature of the CLL that helps you understand how mature or immature the CLL cells are.

In general, mature cells tend to behave a little bit more predictively, and in ways that behave a bit better with therapy. So, the more mature cells are actually mutated IGHV, and I know that’s backward, because usually we think of mutated as being back. But in this case, mutated is actually those cells that are a bit more mature, and that just has to do with how white blood cells develop in our body. If it’s IGHV-unmutated, those tend to be the more immature cells that can behave a little more erratically.

Katherine:                  

Which tests need to be repeated over time?

Dr. Roeker:                 

So, IGHV mutational status never changes, so that one does not need to be repeated. TP53 mutational status, FISH, and karyotype or SNP array, are ones that I tend to repeat before we start any therapy. So, at the time that you’re going to start your frontline therapy, and then if you have the disease come back and need to be treated again, I usually repeat those tests because those can change over time.

So, that’s both FISH, karyotype or SNP array, and the TP53 mutational testing.

Katherine:                  

Okay. So, it sounds like it’s important for patients to make sure they’ve had this testing. What do the test results reveal about a patient’s prognosis?

Dr. Roeker:                 

So, IGHV mutational status, like I said, really helps us understand how to approach therapy. In general, CLL is a disease that we are increasingly managing with targeted medicines, so drugs that really manipulate the cell biology to either stop the growth of cells or kill the cells so that they pop open. And that has been a trend that has taken place over the last six or seven years, and definitely has revolutionized the treatment of CLL. There is still a small minority of patients, the patients who have IGHV-mutated disease, and are younger, and have fewer other medical problems, that can still be good candidates for chemotherapy.

And the reason that I say that is because in general, chemotherapy for those young, mutated patients cures a subset of patients, so when we look at long-term studies of FCR, which is a combination of chemo and immunotherapy, there are a subset of patients who have a really long period where their disease doesn’t come back, to the point that we call them cured or functionally cured. That’s obviously a word that has a lot of emotional charge around it, and it’s hard because there’s always the possibility of the disease coming back in the future.

But because of those long-term outcomes, we know that there’s some patients that can really have long-term benefit from chemoimmunotherapy.

For IGHV-unmutated patients, and especially for patients with TP53 mutations or deletion of 17p, chemoimmunotherapy really is not the right answer, with all of the medications that we have available to us now.

Katherine:                  

We have an audience question. Mike wants to know, “What does it mean to have high-risk CLL?”

Dr. Roeker:                 

So, great question, and the interesting thing is that I think the answer to that question is evolving. So, deletion of 17p, deletion of 11q, and TP53 mutation have historically been markers of more aggressive disease or unfavorable CLL. In the era where we only had chemo and immunotherapy, we know that patients had less great outcomes. We know that the treatments tended to not work as well, and patients had disease that tended to come back faster, and things like that.

 That’s all evolving in the era of targeted agents. We have some indication that probably patients who have more aggressive underlying disease biology, meaning disease that’s going to behave less well, kind of regardless of what we treat it with, certainly may derive less benefit, meaning that the treatment will work for less long. That being said, these treatments are still really effective for our patients who have traditionally high-risk disease. So, I think it still remains to be seen, in terms of long-term outcomes and what to expect for patients that have these traditionally high-risk characteristics.

Katherine:                  

So, now that we understand how these tests affect prognosis, let’s discuss how they can affect treatment options. Let’s run through a few potential results so we can understand how you might approach each patient type. If someone has deletion 17p, what is the approach?

Dr. Roeker:                 

So, there are two totally reasonable frontline treatment options.

So, BTK inhibitors, which are – the current approved ones are ibrutinib and acalabrutinib, are completely a reasonable approach in the frontline setting, meaning the first treatment that someone gets, and those are pills that you take daily. For ibrutinib, it’s once a day. For acalabrutinib, it’s twice a day, for as long as they’re working. And the idea is, with this approach, you keep on those medicines, and they keep the disease suppressed. So, that’s the first option.

The second totally reasonable option is a combination of venetoclax and obinutuzumab. So, venetoclax is a pill and obinutuzumab is an IV medicine, and the way that this was studied was a total of one year of therapy. So, from the time you start until you’re done with all of your treatments, that’s a one-year course. And the drugs have different side effect profiles, and depending on other medical problems, patient preference about, let’s just take a pill and that’s easy, versus the combination of pill and IV medicines, either can be a completely reasonable choice.

It just depends a lot on patient and doctor preference.

Katherine:                  

What about the TP53 mutation?

Dr. Roeker:                 

So, both of those treatment options seem to work very well for TP53-mutated patients. We had that discussion about the possibility of chemoimmunotherapy for a small minority of patients, and for patients with a TP53 mutation, using chemoimmunotherapy up front is probably not the correct answer. It’s better to go with one of the targeted drug approaches.

Katherine:                  

You mentioned, Dr. Roeker, the IGHV mutated and unmutated. How would you approach each patient type, if a patient is IGHV unmutated?

Dr. Roeker:                 

So, IGHV-unmutated is the same discussion. Chemoimmunotherapy is probably not going to provide a durable, meaning it’s not going to last for a long time. We’re not going to achieve that potential cure. So, for those patients, either the BTK inhibitor approach, or the venetoclax/Obinutuzumab approach is completely a reasonable one to take.

Katherine:                  

And if they’re IGHV-mutated?

Dr. Roeker:                 

IGHV-mutated patients who are young and don’t have a lot of other medical problems, that’s when we add in the third option of chemoimmunotherapy. For many patients, it’s not wrong to choose either a BTK inhibitor or venetoclax/Obinutuzumab, but it does add in that third potential option of chemoimmunotherapy.

Katherine:                  

Are there other markers that patients should know about?

Dr. Roeker:                 

I think those are the big ones.

So, TP53 mutation status, FISH, and karyotype kind of gets you most of them. Some centers do additional next-generation sequencing of other genes that have been associated with higher-risk disease, though really understanding how to interpret those results still remains somewhat unclear, and that’s still an area of research that people are doing, to really understand what those other mutations really mean for people.

Katherine:                  

What about the impact of testing, overall? Why is it so important?

Dr. Roeker:                 

So, as we’ve moved from a disease that was really only treated with chemoimmunotherapy, to one that has targeted drugs available, knowing your IGHV mutational status really impacts what your frontline treatment options are. That’s the major therapy-defining risk factor. The other mutations help you know what to expect. So, for patients who have deletion of 17p or TP53 mutation, it’s possible that the treatments are going to, overall, work for a shorter period of time.

All that being said, every person is an individual, and it’s hard to predict exactly how long someone’s going to respond, from an individual basis. So, what I tell my patients is, “I could tell you what 100 of people with exactly your same disease would do, on average, but I can’t tell you exactly what’s going to happen for you. And that’s a journey that we’re going to take together and really understand over time.”

Katherine:                  

These are really great points, Dr. Roeker. Now, we’ve talked about this a little bit. What are other important factors to consider, like a patient’s age, that can help them access the best treatment for their CLL?

Dr. Roeker:                 

So, age is important. Other medical problems is actually a very important consideration.

So, these medications have different side effect profiles and behave differently in different people. So, the BTK inhibitors, specifically ibrutinib is the one that we have the most data on, has cardiovascular side effects, so it can cause atrial fibrillation. It can cause high blood pressure. So, for patients who have preexisting heart disease, or preexisting atrial fibrillation that has been hard to control, or blood pressure that has been hard to control, for those people, I think adding in a BTK inhibitor can be a bit more of a higher risk situation than in somebody without those preexisting problems.

Venetoclax is a pill that causes the cell to burst open rapidly, and it kills cells very quickly. Because of that, the major side effect is called tumor lysis syndrome, and tumor lysis syndrome is basically the cell opens up and all of the salt inside of it goes into the bloodstream.

And that salt can actually be really hard on the kidneys. So, for people who have kidney problems, venetoclax can be somewhat more challenging to use and just requires a higher level of vigilance. So, for patients who have preexisting kidney disease or the idea of a lot of monitoring and things like that, is more challenging. Then maybe the BTK inhibitors are a better choice.

Katherine:                  

How do you monitor whether a treatment is working?

Dr. Roeker:                 

So, a lot of it has to do with the CBC, so your normal blood count, and what we’re looking for is improvement in hemoglobin and improvement or normalization of platelet count. And for many people, those, either anemia or low platelets, are the symptoms that drive people to be treated in the first place, so we’re looking for those parameters to get better.

With a lot of people with CLL, totally understandably, because it’s the number that’s the most abnormal, really focused on white blood cell count. 100% understandable.

I always tell people that that’s actually the part of the CBC that I care least about, and the reason is that, for patients on BTK inhibitors, we expect to see the white blood count actually get higher before it gets less high. That’s actually just a sign that the drug is working and it’s pulling CLL cells from the lymph nodes into the bloodstream. So, that’s actually a good sign that it’s working, and that lymphocyte count, at least in the beginning, isn’t a great marker of how well the drug is working.

The other thing that’s important is the physical exam, so looking for whether any lymph nodes that were enlarged have normalized or gone away, and also feeling the sides of the spleen, because the spleen can become enlarged with CLL, and it’s important to make sure that’s normalizing, as well.

And then the last piece is talking to people, so making sure that if they were having fatigue, or fevers, or night sweats before they started treatment, to make sure that those symptoms have gone away. And that’s kind of the three things that I use. I use the blood counts, the physical exam, and the interview with a patient to really understand how their disease is responding.

Katherine:                  

Dr. Roeker, why is it important for patients to speak up if they’re experiencing side effects? I know that they sometimes feel like they’re bothering their healthcare team.

Dr. Roeker:                 

Thank you for that question, because it’s really important point. Side effects are easiest to manage when you catch them early. So, when people have, for instance, muscle pain or joint aches, I have lots of tricks up my sleeve to help people, but I need to know about it. So, if people don’t tell me until they have joint pain that’s so bad that they’re not able to exercise or not able to get out of bed easily in the morning, that’s taking it – it’s gone on for a while at that point, and it’s pretty far down the line.

First of all, you wouldn’t have had to suffer for that long because we have ways of fixing it, and second, it’s always harder to fix a problem once it’s further down the line than earlier on. So, I talk to people about what side effects they might experience and what to expect, and then we talk about different management strategies to really nip it early so that we’re not dealing with a really huge problem down the line.

Katherine:                  

We have a question from our audience. Maria asks, “I just found out that I will need to undergo treatment again. I was previously treated with FCR. Does that impact my options now, going forward?”

Dr. Roeker:                 

Great question. So, FCR was a really common treatment strategy before we had all of the drugs that we have available now. We have good data to say that both BTK inhibitors and venetoclax-based treatments work after chemoimmunotherapy. In fact, those were the patients in whom these drugs were really initially studied, so we actually know better in that group of patients how they’re going to work, than in the patients who have never been treated with them, in terms of the amount of data and the long-term follow-up that we have.

So, most likely, your provider will still talk to you about kind of the two therapeutic option being a BTK inhibitor-based approach versus a venetoclax-based approach, and either are completely appropriate in that setting.

Katherine:                  

We have another question from our audience. Eileen is currently in active treatment for her CLL, and she wants to know, “Is the COVID-19 vaccine safe for her?”

Dr. Roeker:                 

Great question. So, here is my take on COVID vaccines. We have great data on the safety of these vaccines, so the risk of a life-threatening allergic reaction is very, very low, less than one in a thousand. We know that it can cause some irritation at the injection site, so pain in your arm. We know that it can cause some kinda flu-like, blah symptoms for a couple of days, totally fine to take ibuprofen and kinda get yourself through that period.

But from a safety perspective, I don’t have concerns about these vaccines. There’s a lot of social media coverage on long-term implications that are either not based on data, at all, and just speculation, and people who are trying to raise alarm, or people who are really bringing up bad things that are happening to people really far out from the vaccine. And I think it’s really hard to attribute that to the vaccine. Obviously, any time there is a new technology, there’s the possibility of things happening, and we’re going to know more with time, but I think, overall, from a scientific perspective, there is no data that makes me worried about the safety of this vaccine.

The efficacy question, I think, is more of an open question, and the reason I say that is two-fold. The first is, we know that patients with CLL who get other vaccines, some get 100% coverage, some get zero percent coverage, and some are somewhere in between.

And it’s hard to predict who is going to fall where. So, that’s the first piece. The second piece is, we’ve looked at patients who had CLL and got COVID, and we saw if they made antibodies, which is kind of a marker of an immune response, and it’s not consistent that every patient who got COVID makes antibodies.

So, the combination of those two pieces of data makes me question exactly how well they’re going to work. So, what I’m telling my patients is, “Definitely go ahead and get it. I think it’s safe. And then pretend that you didn’t get it.” So, I know that’s hard advice to hear, but continue wearing a mask, continue social distancing, and continue to wash your hands. And then, every interaction you have is a risk-benefit discussion or decision. So, that’s different for every person, but in general, I recommend that people continue being cautious.

Once the whole population around you is vaccinated and we have less virus circulating in the community, that’s when it’s going to be substantially safer. So, definitely, I recommend that people get it, regardless of whether you are on watch and wait, getting treatment, have just finished treatment, whatever it is, but I do think there’s reason to be cautious even after getting vaccinated.

Katherine:                  

Are there symptoms or issues CLL patients should be looking out for, post-vaccine?

Dr. Roeker:                 

Not particularly, beyond what people are getting in kind of the general population. If you’re having a lot of those kind of flu-like symptoms, just talk to your provider to make sure that ibuprofen is safe, because if your platelets are really low, that can cause bleeding. But Tylenol is typically pretty safe, and talk to your doctor about which medicines are kinda best for you to take in that situation, but no particular concerns in patients with CLL.

Katherine:                  

Okay. Thank you for the clarification. As I mentioned at the start of this program, patients should insist on essential CLL testing. As we conclude, I think it’s important to point out that some patients may not know if they’ve received these important tests, so how can they take action?

Dr. Roeker:                 

So, the next time you’re at your doctor, ask, “I just want to know more about the prognosis of my CLL, and can we talk through the genetic markers of my disease, to help me understand what to expect?” That’s kind of code for, “Let’s go through all of these test results,” and it also – if you have a provider who doesn’t routinely test them at diagnosis, and for instance, just tests before treatment, they can also kind of give you their sense of when they do the testing, so you know what to expect. And I think that’s an important discussion to have with your provider, for sure.

Katherine:                  

Are there key questions that patients should ask their physicians?

Dr. Roeker:                 

I’m always impressed with the questions that people come up with. I think one of the best is, what should I expect, based on what we’re doing now? It’s always a hard question to answer because, obviously, for any patient, it’s so individualized, but I think understanding what to expect, as a general sense, is a good way to approach both treatment and prognosis, and all of those kinds of things.

Katherine:                  

I’d like to close by asking about developments in CLL research and treatment. What’s new that you feel patients should know about?

Dr. Roeker:                 

So, there are a lot of exciting drugs coming up in CLL. We have the BTK inhibitors, ibrutinib and acalabrutinib approved. We have more BTK inhibitors with different side effect profiles that are in development.

And there’s also a new class of drugs called noncovalent BTK inhibitors, which seem to work well, even when prior BTK inhibitors have stopped working. So, that’s a really exciting development. There is also just lots of studies about how we combine drugs to maximize efficacy while minimizing side effects, and all of these studies that are underway are really looking at refining how we approach treatment so that we can treat people very effectively but also minimize their side effects.

And as we have more results available, the treatment paradigm for CLL is going to continue to shift and evolve, and I think there are a lot of exciting things coming, and there’s definitely a lot of reason to be hopeful, that the future of CLL is even brighter than the present.

Katherine:                  

It all sounds very promising, Dr. Roeker. Thank you so much for joining us today.

Dr. Roeker:                 

Thank you so much for having me. I really appreciate it.

Katherine:                  

And thank you to all of our partners. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey, immediately following this webinar. It will help us as we plan future programs. To learn more about CLL and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us.

What Standard Testing Follows a Myeloma Diagnosis?

What Standard Testing Follows a Myeloma Diagnosis? from Patient Empowerment Network on Vimeo

What tests will you have following a myeloma diagnosis? Are there additional tests you should request? Dr. Joshua Richter provides an overview of key testing for myeloma and why each test is necessary.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

See More From INSIST! Myeloma


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Myeloma Treatment: When Should a Clinical Trial Be Considered?

Is the COVID-19 Vaccine Safe for Myeloma Patients?


Transcript:

Katherine:

What standard testing follows a myeloma diagnosis?

Dr. Richter:

So, the standard testing that follows a myeloma diagnosis is multifaceted. So, the first one is blood work. And we draw a lot of blood tests to look at the bad protein that the cancer cells make. So, we send tests like a protein electrophoresis which tells us how high that bad protein is. We send immunofixation. That test tells us what type of bad protein it is. You’ll hear names like IgG kappa and IgA lambda.

These are the different types of bad proteins made by myeloma cells. Oftentimes, we’ll send urine tests to find out how much of that bad protein that was in the blood is coming out in the urine. We will, typically, do a bone marrow biopsy. It’s a test where we put a needle into the back of the hip bone to look at the marrow itself. And we’ll use that marrow to figure out how much myeloma there is, any other characteristics like the genetic changes in those cells.

The other big thing is imaging. So, the classic imaging that we do with myeloma is something called a skeletal survey. It’s, basically, a listing of X-rays from head to toe. But nowadays, we have newer techniques, things like whole body low-dose CAT scans, something called a PET-CT scan, and MRI scans. And your care team may have to figure out which one is right for you at what given time.

Katherine:

Mm-hmm. Are there additional tests that patients should ask for?

Dr. Richter:

Absolutely. One of the most important things from myeloma has to do with the genetic risk stratification.

So, for almost all cancers, the staging has a very big impact. And people will often think of cancer in stages I, II, III, and IV, and they’re managed very differently depending upon what stage it is. Myeloma has three stages, stage I, II, and III. But the most important thing is, actually, beyond the staging is what’s called the cytogenetics risk stratification. So, it’s really important when the bone marrow is sent to be sure that it is sent for, kind of, advanced techniques. Because you really want that snapshot of exactly what the genetic profile is, because that gives us information of A) how to treat, and B) prognostic, you know, who will tend to do better or worse based on this information. And even though that may not tell us which drugs to use, specifically, it may say, should we do something like a transplant or not? Should we consider a clinical trial early or not?

Katherine:

I see. How do test results affect treatment choices?

Dr. Richter:

So, test results can affect treatment choices in a number of ways. Probably, the most common one is thinking about the routine blood tests like your CBC or complete blood count and your chemistry, which looks at things like your kidney function. Some drugs tend to have more toxicity to the blood counts. So, if your blood counts are very low, we may choose drugs that don’t lower the blood counts very much.

Kidney function which we, usually, measure by something called the creatinine. Creatinine is made by the muscles and cleared out by the kidneys. So, if your kidneys aren’t working very well, you don’t pee out creatinine, and that creatinine level will rise in the blood. If your creatinine level is high, we may choose certain drugs that don’t affect the kidneys or not metabolized or broken down by the kidneys.

The genetic studies that we use – we’re not quite at this base yet where we can say, if you have this genetic abnormality in your myeloma, we should use this drug except there’s some really great data on the cutting edge about a drug called venetoclax.

Venetoclax is a pill that’s used to treat other diseases like lymphoma and leukemia. And it turns out that people who have what’s called a translocation (11:14) which means part of the 11th chromosome and part of the 14th chromosome in the cancer cells swap material.

Those people respond amazingly well to venetoclax. So, we’re starting to have what we would call precision medicine where we find your genetic abnormalities, not that you got from your parents or passed to your kids, but the genetics inside the tumor cells to tell us which treatments will work best for you.

How to Play an Active Role in Your CLL Treatment Decisions

How to Play an Active Role in Your CLL Treatment Decisions from Patient Empowerment Network on Vimeo.

How can you partner with your healthcare team to feel confident in your CLL decisions? In this webinar replay, Dr. Matthew Davids discusses CLL treatment approaches, developing research and tools for partnering with your healthcare team. Dr. Matthew Davids is the Director of Clinical Research in the Division of Lymphoma at Dana-Farber Cancer Institute.

Download Guide

See More from Engage CLL


Related Resources:

 

Which CLL Treatment Approach Could be Right for You?

Transcript:

Katherine:                  

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to explore the factors that guide CLL treatment decisions, including your role in making those decisions. 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 the webinar. And at the end of this program, you will receive a link to a program survey. This will allow you to provide feedback about your experience today, and it will help us plan future webinars.

Finally, before we get into the discussion, please remember that this is not a substitute for seeking medical advice. Refer to your own healthcare team. All right, let’s meet our guest today. Joining me is Dr. Matthew Davids. Dr. Davids, would you please introduce yourself?

Dr. Davids:                  

Hi, Katherine. Thanks so much for having me. It’s great to be with everyone today. I’m Matt Davids. I’m a CLL-focused physician based at Dana Farber Cancer Institute in Boston, and I’m also an associate professor of medicine at Harvard Medical School. And I get to wear many hats here. First and foremost, I take care of patients, particularly patients with CLL, but I also have some administrative roles. I direct our clinical research program in the lymphoma division. I also run a research laboratory focused on CLL and other lymphoid cancers, and I run about a dozen clinical trials mostly focused on developing new treatment options for patients with CLL.

Katherine:                  

Wow. Sounds like you’re a busy guy. I’m glad you have the time to join us today.

Dr. Davids:                  

My pleasure.

Katherine:                  

Let’s start with a question that’s on the mind of many of our audience members. Is the COVID-19 vaccine safe for CLL patients?

Dr. Davids:                 

Very timely question. The simple answer is yes. There are now actually three different vaccines that have been granted emergency use authorization by the FDA.

And I would say that so far, we’ve seen clinical trial evidence suggesting these are very safe vaccines in the general population.

Our own experience with our own CLL patients so far has also suggested safety, so I think it’s very important that our CLL patients get vaccinated as soon as they can. I think the bigger concern more than safety is on the efficacy side of the vaccine, meaning how effective are these vaccines going to be for CLL patients? That’s not something that we know yet from the larger clinical trials that have been done. So, those numbers you see quoted, 95 percent protective, that’s in the general populations.

We do worry a bit based on our experience with other vaccines in CLL patients that they may not be quite as effective, but we don’t know that yet. Fortunately, that’s something that we’re studying now, both at our center and in some nationwide efforts, to look for example at the antibody production that CLL patients can make before and after vaccination. I’m hopeful that over the next few months we’ll start to learn about how effective these vaccines are specifically for CLL patients.

We certainly expect they will have some benefit, so that’s why we recommend vaccination for all of our CLL patients. But once patients are vaccinated, it doesn’t give them a free pass to then take their masks off and go back to normal life. Particularly CLL patients I think need to be careful even after vaccination to continue to do social distancing, hand hygiene, and all these things.

Katherine:                  

Is there one type of vaccine that’s more suited for CLL patients?

Dr. Davids:                 

Nope. As far as we can tell, all three of the approved vaccines so far are safe and should have some good effects for CLL patients.

There’s no benefit of one versus the others, so the best one to get is the one that’s in your muscle and injected. Whatever you can get access to, that’s the best one for you.

Katherine:                  

Dr. Davids, have there been any recent developments in CLL treatment and research that patients should know about?

Dr. Davids:                 

Yeah. We could spend a few hours on this, but I’ll try to summarize it. There’s a lot of exciting developments in the field. and I think we’re going to get into some of the specific treatments in a few minutes, but I would say at a high level obviously, over the last decade the entire field of CLL treatment has been transformed. Whereas we only had chemotherapy-based approaches before, now we have a whole number of different drugs that we call novel agents. And the reason why they’re novel is that they target the CLL cells, but they spare the other cells in the body, so there’s less collateral damage there. What that means is that they have fewer side effects, and they’re more effective, so it’s really a win-win situation for patients.

There’s kind of been two main approaches for this.

One is to start a novel agent drug and to continue it for as long as it’s helping, which fortunately for most patients is a long time, many years. And then, a newer approach is actually to do what’s called time-limited therapy where you start usually at least a couple of these different novel drugs together but hopefully achieve what we call a very deep remission, meaning excellent shrinkage of lymph nodes and improvement of blood counts and bone marrow disease. And by getting these very deep remissions the idea is we can do a finite period of treatment, whether it’s one year or two years, it kind of depends on the regimen. And then, stop therapy and hope that patients can then enjoy many years of remission while off therapy, which can be nice in terms of reducing side effects and costs and all these other things.

So, those are the biggest developments in the field right now, the continuous novel agent therapy and time-limited novel agent therapy. And a lot of the clinical trials that are getting off the ground now are starting to compare these two strategies to figure out really what’s the optimal way to treat CLL patients.

Katherine:                  

How can patients stay up-do-date on developments like these?

Dr. Davids:                 

It’s definitely challenging. It’s challenging even for us who are in the field to keep up with things on the academic side. I think for patients, seeking out patient-friendly sources of information on the web are helpful, but sometimes it can be hard to know what’s reliable information on the web. So websites like this and programs like this I think can be very helpful. Another resource that a lot of my patients find helpful is the CLL Society, so www.cllsociety.org. Brian Koffman really curates a lot of the new developments in the field on that website nicely. He interviews a lot of different CLL experts in this short format that can be very digestible for patients. Patient Power is another great website. So, there are a bunch of them out there, and I think those can be a great resource for our patients.

Katherine:                  

When a person is diagnosed with CLL they have a whole healthcare team. Who’s typically on that team?

Dr. Davids:                 

It’s definitely a multidisciplinary team.

Usually there’s an oncologist-hematologist who’s leading the team as a physician, but there’s a very large team of other people who are involved, whether it’s an advanced practice person such as a nurse practitioner or a physician’s assistant. They’re often very closely involved with the day-to-day patient care. There’s nurse navigators in some places that can help with getting access to these novel agents and with looking into clinical trial opportunities. There’s pharmacy folks who are very helpful sometimes in checking in on side effects, and advising on dosing, and so forth.

That’s more on the provider side of things. But, of course, the care team really includes the caregivers for the patient, whether it’s family members or friends, who are really a crucial part of this. The field is very complicated, and one of the challenges with COVID recently is that I’ve always invited family members and friends to come to visits with patients, because I do think it’s helpful to have many people listening. And that’s been hard because we’ve had to restrict visitors usually to either no visitors or one visitor because of COVID precautions.

Even if that’s the case, you can still have people dial in by phone or use technologies like FaceTime to try to have them there with you, because I think having that extra set of ears can be helpful as you hear all this information coming at you from your oncologist.

Katherine:                  

Yeah, absolutely. So, it really does sound like it’s a whole team approach. We have a question from the audience. Linda writes, “I’ve heard that CLL doesn’t need to be treated right away. Is that true?” 

Dr. Davids:                 

That is true for the majority of CLL patients, and it’s actually a very counterintuitive thing. We’re conditioned that if you have cancer that it’s important to be proactive and get rid of it as quickly as possible, the sooner the better, and that is actually not the case in CLL. And we didn’t just take a guess that that’s the best approach. This is actually something that’s been studied in clinical trials. There were several clinical trials launched in the ‘70s and ‘80s looking at an early intervention strategy using a chemotherapy-based approach to see if treating at the time of diagnosis would be better than waiting until patients developed more significant symptoms.

And all of those studies did not show a benefit to early intervention.

Now, more recently those studies have been challenged as somewhat out of date, which is a fair criticism because they used an older chemotherapy drug. And so, there is a newer study now going on in Europe that is looking at early intervention with the drug ibrutinib, which is one of our novel agents for CLL, looking to see if early intervention with ibrutinib, particularly for patients who have a higher risk form of CLL, may be beneficial.

But we have seen some data now already presented from this study that do not show any improvement in how long the patients live by treating with ibrutinib early, and we do see some of the typical side effects that we’re accustomed to seeing with ibrutinib. So, even with the newer data that we’re seeing, we still do not recommend early intervention for patients with CLL.

Katherine:                  

I’ve heard this term “watch and wait.” What does that mean?

Dr. Davids:                 

Yeah, it’s not the best term because it’s very passive. That refers to this observation strategy. I like to think of it more as “active surveillance.” It seems more proactive because you’re doing something about it.

You’re really checking the blood counts, you’re getting your physical exam, you’re checking in on symptoms, these sorts of things, and really keeping a close eye on the disease. And that’s the approach that we like to take with our patients to really keep them engaged, making sure they’re staying up-to-date on their screenings for other cancers, making sure they’re getting vaccinations, these sorts of things are all the things we do with active surveillance.

Katherine:                  

How is someone monitored during this watch-and-wait period?

Dr. Davids:                 

It varies depending on individual patients. We’ve alluded to the fact that there’s different genetic subgroups of CLL already, so there are some patients that have higher-risk disease. The example of that usually is deletion 17p that people may have heard of on the FISH test. For those patients I usually am seeing them every three months or so, physical exam, checking on their history, checking their bloodwork. But there’s quite a few CLL patients who have lower-risk disease. If they have for example mutated IGHV, if they do not have the 17p for example, those patients may be able to be seen once every six months or so with a similar setup.

 I don’t routinely get CAT scans on a regular basis for most patients. Most patients don’t need bone marrow biopsy tests unless they’re starting treatment. So, it’s mostly it’s exam, talking to patients, and checking the bloodwork.

Katherine:                  

Okay. So, how does CLL progress? When do you know when it’s time to treat?

Dr. Davids:                 

The stages of CLL involve the progression of the disease. When we first meet patients, often they only have cells circulating in the blood, and that’s called stage 0 disease. It’s one of the few cancers where there’s actually a Stage 0 before even Stage I, and the reason for that is that many patients can go for years on Stage 0 disease. But as the burden of the CLL cells begin to accumulate in the body they can start to collect in their lymph nodes, and the lymph nodes can start to swell up whether it’s in the neck or the armpits or elsewhere. That’s stage I disease.

They can accumulate in the spleen, which is an organ in the abdomen. It’s kind of a big filter for your bloodstream, and as the filter traps more of these lymphocytes the spleen can slowly enlarge over time. That’s stage II disease.

And then finally, the CLL cells can get into the bone marrow, which is like the factory for making your blood cells. And if the factory floor gets all gummed up with CLL cells it can’t make the normal red cells, that’s called anemia. Or it can’t make the normal platelet cells, that’s called thrombocytopenia. And when we start to see those more advanced stages III and IV of CLL, that usually does require treatment. And what the treatment does is it clears out the factory floor and it allows for the normal machinery to make the normal blood cells again. So, that’s one of the more common reasons why treatment is needed is due to anemia and low platelets. Second reason can be if the lymph nodes or spleen get so bulky that they’re uncomfortable or threatening organs internally. We want to treat before that becomes a real threat.

And then, the third thing that usually happens as the disease progresses, patients can develop some symptoms, what we call constitutional symptoms. These can be things like unintentional weight loss, drenching night sweats that are happening on a consistent basis, and those sorts of things. So, if that’s happening at the same time as these other factors are progressing, those would be reasons to treat.

And notice that one thing I did not say is the white blood cell count itself.

That’s a common misconception. Some people think that as the white blood cell count goes higher – and people use all different thresholds, 100, 200 – that by crossing that threshold you need to start treatment. And in fact, that’s not the case. We have many patients whose white blood cell count can get very high but then it can kind of level off and plateau for a period of several years, and as long as they don’t meet those other treatment indications, they don’t need to be treated just based on the white count alone.

Katherine:                  

Hmm, okay. Well, once it’s time to treat, of course then it’s time to think about treatment options. Let’s walk through the types of treatments that are used today to treat CLL.

Dr. Davids:                 

As I alluded to before, we historically have had chemotherapy-based approaches to treat CLL. And that was an effective way to temporarily put the disease into remission, but it had a lot of side effects and inevitably the CLL would come back. And the challenge particularly with chemotherapy-based approaches it that when the CLL does come back after chemotherapy, it tends to behave more aggressively and be harder to treat.

So, there have been quite a few studies over the last few years trying to figure out ways that we can avoid using chemotherapy as the first treatment, and this can involve treatments such as monoclonal antibodies. People may have heard of rituximab or a newer drug, obinutuzumab. There are the inhibitors of the B-cell receptor pathway, and this is for example ibrutinib, which targets a protein called BTK, also a newer one called acalabrutinib, which targets BTK. And then, I mentioned at the beginning these fixed-duration therapies that stop after a period of time. Many of those are based on a newer oral drug called venetoclax, which when we give it as a first therapy, we give in combination with that antibody obinutuzumab.

So, a bit of an alphabet soup. I know it gets confusing with all the different treatments, but the good news for CLL patients is, 1.) we have a lot of options, which is great, 2.) we don’t necessarily need to use chemotherapy anymore, and in fact I use it pretty rarely these days. One situation where I do still consider chemotherapy is for younger patients – which in the CLL world is sort of under age 60 or so – if they have very favorable biology to the disease, in particular this mutated IGHV.

That’s a scenario where the older chemotherapy regimen, FCR, can be very effective. It’s a six-month treatment, and we have patients with those molecular characteristics who are now 12, almost 15 years out from their initial six months, and they’re still in a complete remission. So, many of those patients have been functionally cured of their CLL from the six months of treatment. But again, there are some risks to that approach. We worry about other cancers that may be more likely after receiving FCR. We worry about infections, and particularly in the COVID situation, we worry about COVID infection in patients on chemotherapy.

So, it’s been pretty rare that I’ve been using that approach these days. I’ve been opting more for the novel agent-based approaches. So, often now the conversation as an initial therapy comes down to, “Do you prefer more of a continuous treatment strategy with a BTK inhibitor drug like ibrutinib or acalabrutinib, or do you like the idea of a time-limited therapy with one year of venetoclax in combination with obinutuzumab?” And I would say there’s pros and cons to both approaches, and we don’t know which one is the optimal one for CLL patients to start with, but probably I think most patients at some point in their lifetime are going to need one therapy or the other.

So, maybe in the end it doesn’t matter too much which one you start with if you’re going to get both eventually anyway. But we don’t know that yet.

Katherine:                  

Right. Where do clinical trials fit in with the treatment approaches?

Dr. Davids:                 

So, clinical trials are really how we’ve made all these advances in CLL over the last decade. It’s how we learn about new treatments. It’s how we learn about how to optimize the treatments that we have. I think sometimes patients have a misconception that clinical trials are a last resort, the idea that you’ve exhausted all the standard options and then you go to a clinical trial as your last hope. But I actually like to kind of turn that on its head and say that clinical trials are actually the first resort, the first best option for patients. Whenever patients can get access to a clinical trial at any stage of their disease, I would really encourage them to consider it.

We have quite a few clinical trials now in the frontline setting, meaning as an initial treatment for CLL, including some that are in development and will open soon. And these are the studies that are going to really help us define what the optimal regimens are. What’s the optimal sequence of these different novel agents?

And in CLL, really, we’re at a point where the research on the disease is so mature that when you’re in a clinical trial you’re either going to be on one regimen that you know you’re getting and you know it’s going to be an effective regimen, or you might be in a comparative trial where you could be randomized to one of two or three different regiments, but you know that each one of those regimens is one that we think is a great regimen. We just don’t know which one is optimal for individual patients. So, this is not a situation where there’s placebo-controlled trials where you don’t know if you’re going to get an active treatment or not. CLL is an area where we design our clinical trials so that all patients are going to be benefiting from cutting-edge approaches.

And so, not all patients have access to trials, and that’s okay. Again, we’re fortunate that we have many good options that can be given locally, but I do encourage patients even if they’re only able to travel to a CLL specialist once to have an initial consultation to think about doing that to get a CLL specialist on your team, so to speak. That way they can identify clinical trial options that may be a good fit, and even if not, they can advise on what the optimal treatment options are to receive locally with your own oncologist.

Katherine:                  

How do patients find out about these clinical trials?

Dr. Davids:                 

I do think the best way is through a CLL specialist because certainly they would have a great pulse on the trials, they have available at their own center. They should also have a sense for what trials are available maybe at other centers. Some of that can also be, there’s a great resource through The Leukemia & Lymphoma Society where they can help navigate patients toward specific trials that may be applicable to them.

There’s also a website called clinicaltrials.gov. It can be a little challenging if you’re not familiar with it to navigate the site, but it is actually pretty straightforward. You can put in the disease and look at different options for trials based on different drugs, for example. They’ll list the eligibility criteria for the trial. That’s often I find a way that patients can begin to identify whether they may be a candidate. You can’t tell from the website whether you’re definitely a candidate or not. You really need to partner with an investigator who’s on the trial to learn that, but it certainly can be a good starting point to figure out what’s out there.

Katherine:                  

With CLL, what are the goals of treatment?

Dr. Davids:                 

I like to say to patients, “The goals are to make you live longer and live better.” You want to obviously have treatments that prolong life, but you also want to have treatments that are helping with symptoms, and giving patients more energy, and making them feel better, and protecting them from some of the risks of the disease. And so, I think the goals do vary a bit based on the stage of life that patients are at.

I see a lot of patients in their 70s and 80s, and in those patient’s symptom control, having the disease be in a good remission, allowing them to live their life is a good goal. I sometimes see patients in their 40s and 50s, and some of those patients want to be a bit more aggressive and try to do a strategy that will get them a very long-term remission, and even potentially explore potentially curative strategies.

If I have a higher-risk patient with deletion 17p who’s young and fit, and they’ve already had some of the novel treatments, that’s where we start thinking about clinical trials of some of the cellular therapies like CAR-T cells that people may have heard of where you use the T cells from the patient to try to use that as a therapy to kill off the disease. Or even a bone marrow transplant is something that we have used historically in CLL. We don’t use it as often now, but for younger patients with high-risk disease it’s still a consideration to try to achieve a cure of the CLL even though the risks of that are significant.

It sounds like there are several factors to weigh then in making this decision. Lately we’ve been hearing the term “shared decision-making,” which basically means that patients and clinicians collaborate to make healthcare decisions.

And it can help patients take a more active role in their care. What are your thoughts, Dr. Davids, on how best to make this process work?

Dr. Davids:                 

Yeah, I fully support that model. I think for most patients it’s very helpful to be an important decision maker. Really the patient is the ultimate decision maker to say what they want for their own treatment. And sometimes it’s hard for me to predict what a patient will want for themselves, so I see my role for most patients as providing the information that they need to make the best decision possible for themselves.

I do try to steer patients a bit in the directions that I think they should be thinking. I’m not going to necessarily present a laundry list of things to patients. I’m going to try to narrow it down to what I think are the most reasonable choices for a patient to make.

I feel that’s part of my job. I do still have patients who just say, “Just tell me what to do,” and I respect that, too. Not all patients want to be part of shared decision making, and they just want me to decide, and that’s fine. But I do find that most patients like the idea of having a voice and being the one to decide, and that way I can help to guide them, but ultimately, it’s up to them.

Katherine:                  

Well, speaking of patients having a voice, are there questions that patients should consider asking when they’re thinking about a proposed treatment plan?

Dr. Davids:                 

Yeah. I think some of the key ones revolve around basic stuff, but sometimes it’s hard to think of it in the moment. But thinking about, what are the risks of this therapy? What are the specific side effects that are most common? When you look at a package insert or you look at a clinical trial consent form, you’re going to see 100 different side effects listed. I always promise patients, “You won’t have every single side effect that’s listed here, but you may have a couple of them.” And again, my role often is to identify which are the more common side effects that we see and how can those be managed?

And then, I think often you’re just asking simply about what are the potential benefits of this therapy? What are the odds that I’m going to get into remission? How long is this remission likely to last?

And then, something that is often challenging for patients to think about – it can be challenging for me as well – is to think about what’s the next step? So, I think a good question to ask is, “If I choose Therapy A, what happens if I need therapy again in a few years? What are the options at that point?” because we’ve been talking so far mostly about what we call frontline therapy, making that initial choice of treatment. But then, once you get into what we call the relapse setting, a lot of the decision of what to receive at that point depends on what you got as the first therapy. And so, trying to think at least one step ahead as to what the next options are I think can be helpful, certainly for the physicians but also for the patients.

Katherine:                  

Do you have any advice to help patients speak up when they’re feeling like their voice isn’t being heard?

Dr. Davids:                 

That’s always a challenging situation, but I encourage patients not to be shy about asking questions.

There’s often an imbalance in terms of the information where the oncologist may know more than the patient about a particular condition. And so, I think reading up and trying to educate yourself as much as you can. Whenever possible, including a family member or friend as part of the visit to also help advocate for you. And then, if you’re not being heard the way that you think you should be, thinking about seeking out another provider who may be able to listen more.

And sometimes that can be again helpful to have a touchpoint with a CLL specialist who may be able to reinforce some of what you’re thinking. If what you’re reading online or seeing online is different from what your oncologist is telling you, that may be a sign that it’s good to get a second opinion and just make sure you’re on the right track.

Katherine:                  

All really helpful advice, Dr. Davids. Before we end the program, what are your thoughts about the future of CLL treatment and research?

Dr. Davids:                 

I’m very optimistic about where things are right now. We’ve gotten to this point where we have so many different effective options, so it’s fun for us to now design this next wave of clinical trials to really try to optimize the outcomes for patients.

One area I’m particularly interested in is a concept called MRD, which we haven’t talked about yet, but minimal residual disease is a way to look even at a molecular level for tiny amounts of CLL that may be left behind after treatments. And so, one of the things I’m particularly excited about is the idea eventually of using what we call MRD-guided therapy.

So, we talked before about continuous treatment. We talked about what we call fixed-duration treatment where everyone gets a year or everyone gets two years. MRD-guided therapy would actually allow us to vary the length of therapy depending on how a particular patient responds. So, some patients may need one year of a particular combination, but other patients may need two years. This could be a way to really individualize therapy for particular patients. It’s also a way to monitor patients who are in remission after they’ve stopped therapy.

And so, there’s another wave of trials looking at, should we be intervening early when patients develop recurrence of their MRD rather than waiting until they’re having progression of the disease? There’s still a lot of unanswered questions about these sorts of approaches, but I think it’s going to help us get even better at treating CLL.

All of this is contingent though upon the fact that patients continue to be interested in clinical trials and enrolling in trials so that we can really push the boundaries and learn even more about the disease. So, again, if no other message comes through, it’s really to think about clinical trials as a way to continue to improve outcomes for all patients with CLL. I think it’s a great situation where both the individual patient who’s participating in the trial can stand to benefit, but then also you can really be giving back and helping others.

Katherine:                  

Dr. Davids, thank you so much for taking the time to join us today.

Dr. Davids:                 

It’s my pleasure. Thanks so much.

And thank you to all of our partners. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. You’ll receive an email when it’s ready. Don’t forget to take the survey immed – don’t forget to take the survey immediately following this webinar. It will help us as we plan programs for the future. To learn more about CLL and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us.

How Can You Advocate for the Best Lung Cancer Care?

How Can You Advocate for the Best Lung Cancer Care? from Patient Empowerment Network on Vimeo.

What is the patient’s role in lung cancer care? Dr. Jessica Bauman discusses the importance of communication with your healthcare team as well as the benefits of taking advantage of supportive care options.

Dr. Jessica Bauman is assistant professor in the department of hematology/oncology and as associate program director of the hematology/oncology fellowship training program at Fox Chase Cancer Center in Philadelphia. Learn more about Dr. Bauman here.

See More From the The Pro-Active Lung Cancer Patient Toolkit

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Key Next Steps After a Lung Cancer Diagnosis: Expert Advice

What You Should Know When Making a Lung Cancer Treatment Decision

What You Should Know When Making a Lung Cancer Treatment Decision

Navigating Lung Cancer Treatment Decisions

 


Transcript:

Katherine:               

Let’s talk about patient self-advocacy. Patients can sometimes feel like they’re bothering their healthcare team with their comments and questions. But why is it important for patients to speak up when it comes to their symptoms and their side effects?

Dr. Bauman:                

So, this, I would say, it’s a partnership. The bottom line is, and if I don’t know that something is going on, I can’t help to solve the problem. And if I don’t know about something, a new symptom that could be, potentially, majorly concerning, patients can also get really sick or even end up in life-threatening situations. And so, ignoring things or just hoping things will go away is not in a patient’s best interest.

I think that it is critical that patients are their own self-advocate. I think that I say that often, and I’ve already said that a couple of times on this, but we don’t know unless we’re hearing from them what’s going on. And so, it is so important for patients to keep us updated if they’re worried about something. Certainly, we see them very frequently, and so they can often tell us at their visits what’s going on. But overall, the in-between time is just as critical because it is often the treatments that we give can cause side effects at any time. And so, it is really important that we know about anything that’s going on and for patients to always give us a call.

I mean, that’s the bottom line is, is that if they’re worried about something, we need to know about it.

Katherine:                   

What supportive care options are there for patients who may have pain management difficulties or even emotional support? Where do they start?

Dr. Bauman:                

So, there are often many different kinds of supportive care for patients. I would say that oncologists, of course, are one layer of supportive care. We do a lot of help with symptom management and often even pain management as well as coping and emotional support. However, there are also other people often within cancer centers that are also available to help. And this includes social workers. It also includes psychologists and psychiatrists.

And then the other thing that I think is really important to mention is that we know for patients who have lung cancer or an advanced lung cancer diagnosis, that integrating a palliative care team – a supportive and palliative care team – early into their diagnosis actually helps them live longer as well as better.

They have better quality of life, and they have decreased problems with mood.

And so, we know that supportive care and palliative care, specifically in lung cancer, is particularly helpful for both patients and their caregivers. And so, it’s important for patients to also know that there is a whole team, that I think of as, sort of, an extra layer of support, that can help them with symptom management as well as with coping with the day-to-day of what can be a devastating diagnosis.

 

 

How Do I Know If My Lung Cancer Treatment Is Working?

How Do I Know If My Lung Cancer Treatment Is Working? from Patient Empowerment Network on Vimeo.

How is lung cancer treatment monitored? Lung cancer specialist Dr. Jessica Bauman explains how regular imaging is used to gauge treatment effectiveness.

Dr. Jessica Bauman is assistant professor in the department of hematology/oncology and as associate program director of the hematology/oncology fellowship training program at Fox Chase Cancer Center in Philadelphia. Learn more about Dr. Bauman here.

See More From the The Pro-Active Lung Cancer Patient Toolkit

Related Programs:

How Can You Advocate for the Best Lung Cancer Care?

How Can You Advocate for the Best Lung Cancer Care?

What You Should Know When Making a Lung Cancer Treatment Decision

What You Should Know When Making a Lung Cancer Treatment Decision

Lung Cancer Treatment Approaches: What Are Your Options?

Lung Cancer Treatment Approaches: What Are Your Options?


Transcript:

Katherine:               

Once a patient has started treatment, how do you know if it’s working?

Dr. Bauman:                

So, we do regular imaging. So, once you have a diagnosis of lung cancer, a CAT scanner will become your friend. In general, depending on what stage of lung cancer you have, you will have a bunch of imaging up front, and then once a treatment plan is put into place, after that treatment has either been completed or started, you will be monitored, in general, regularly for the lung cancer diagnosis. Now, after surgery, that will be for more for surveillance to make sure that the lung cancer doesn’t come back. But if it is more in the setting of a stage IV lung cancer, then the imaging really helps us determine, “Is the treatment working or not?”

And so, after we start a treatment, usually anywhere between six and eight weeks, we repeat imaging to see, “Is this working? Is it smaller? Is it the same? Has it grown?”

And based on that imaging, and based on how the patient is doing with the treatment, we then decide, “Do we continue this treatment, or do we need to change to a new treatment?” And so, we regularly monitor the patient’s cancer through regular imaging.