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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. 

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An Overview of CLL Treatment Types

What Should CLL Patients Know About Clinical Trial Treatment Options?

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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.

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.

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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.

Are Clinical Trials Too Risky? A Lung Cancer Expert Reviews the Facts.

Are Clinical Trials Too Risky? A Lung Cancer Expert Reviews the Facts. from Patient Empowerment Network on Vimeo.

Some patients fear that clinical trials may be too experimental and risky. Dr. Martin Edelman outlines the clinical trial process and addresses myths surrounding trials. Want to learn more? Download the Program Resource Guide here.

Dr. Martin J. Edelman is Chair of the Department of Hematology/Oncology and Deputy Director for Clinical Research at Fox Chase Cancer Center. More about this expert here.

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Transcript:

Patricia:

Here’s the last one that I have on my list here. Clinical trials are experimental and risky.

Dr. Edelman:

Yeah. Well, so is the rest of life. So, there generally – is there risk? Yes. Essentially, every patient is always a trial because we for the most part don’t – even in the disease states where we have very active treatment – so, let’s say – for example, we were talking about the EGFR mutation. So, we have excellent drugs. We have a drug now, osimertinib – outstanding drug, easy to take, low risk of side effects.

The earlier generations – there was a lot of rash, diarrhea. That’s been pretty much done away with. But on average, patients benefit from this drug for about a year and a half.

So, that’s not great if you’re 40 or 50 years old. You want to do better. So, what are our current studies? Well, we’re looking – we’re re-addressing a question that we thought had been answered, but really it wasn’t – about, well, what’s the value of chemotherapy plus this drug? What about the value of other drugs?

So, we can’t promise anybody anything, but our current treatments are still not good enough. There are certain diseases, let’s say Hodgkin’s disease, where you know you’re gonna cure almost all the patients up front or testicular cancer, etcetera, where – again, but thanks to trials, clinical trials, we now are at that stage. We’re not there yet in lung cancer, and the reality is is every patient should really be on a study. I think it’s – and we have this problem now in that our studies have also become far more complicated to enter people in because there are many more variables one has to look at it. What’s the molecular background of the tumor? How many prior therapies?

The condition of the patient, their organ function, etcetera – and the regulatory burden has become much, much greater. But clinical patients are in clinical trials. Let’s look at the question. Are they risky? Well, everything is risky, but we do a lot to manage that risk. Patients who are in studies are observed more closely. We have to. It’s the law. There’s frequently additional personnel assigned. They’re usually getting standard of care plus a new treatment or a new treatment followed by the standard of care or some variation of that.

They’re observed, like I said, much more carefully than we would otherwise. And so, I think actually patients on trials generally will do better, and we actually have evidence. Multiple individuals have looked at this – everything from first-in-man trials or early dose escalation studies, controlled studies – that show that patients, even those on the control arm, generally do better than similar types of patients who are not treated on studies because we just are more careful.

And the physician who participates in trials is generally someone who has a greater knowledge of the disease.

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Patricia:

Let’s talk a little bit about some of the concerns that patients have about the side effects. Let’s see: Side effects are unavoidable.

Dr. Edelman:

Well, that’s not true. As I said, what were the side effects? If you go back a couple decades and you ask patients what were they concerned about, many of them were concerned about nausea and vomiting. And that is largely a thing of the past. Many patients will still have some queasiness with treatment, but even our most nausea-producing drugs – we really do have outstanding drugs for the prevention of that. You have to use them. You have to take them.

It’s very important to give them appropriately. There are very excellent guidelines that are out there. Sometimes, patients are still undertreated, no question about that. Not every drug has industry strong backing. There’s one drug – for example, olanzapine, (Zyprexa) was actually developed as an antipsychotic, and I always tell the patients, “No, I don’t think you’re crazy.”

But it’s at a lower dose, and we have excellent, excellent evidence that that drug given for a few evenings after chemotherapy is extraordinarily effective along with the other drugs in preventing nausea and vomiting. So, that’s one thing.

Hair loss is still somewhat inevitable with certain drugs – the taxanes. But many of our regimens don’t cause hair loss.

Or as I tell folks – only you and your hairdresser will know for sure because its hair on the pillow, but the average person won’t pick you out of a crowd. Those are big concerns still. There still are potentially life-threatening effects from chemotherapy, and we spend a lot of time educating people about that. But those are not inevitable, and it’s actually a minority of patients in lung cancer.

One should not confuse – there are different malignancies. Still, the treatments for say leukemia, though even that’s changing, can be extraordinarily toxic or the bone marrow transplant patients. Many, not just lung cancer, but in the other diseases as well – many of the things that people attribute to the drugs are more due to the disease. So, I always say, “The greatest failure and side effects to the drugs are they don’t work well enough because the side effects of the disease can be considerable.” So, that’s the bigger issue. The immunotherapeutic drugs have a rather interesting set of side effects.

They are clearly initially or frequently better tolerated than the older cytotoxics, which still have an extremely valuable place in the treatment and cure of lung cancer. The immunotherapeutics have clearly been quite beneficial, but their side effects can be subtle and far less predictable and can be very severe. Virtually, any organ in the body can be affected by this. We like to say, “If it ends in ‘itis,’ you can get it from immunotherapeutics.”

So, there are lots of side effects, no question. But they can be managed. They can be prevented. They can be treated. Sometimes, we have to abandon a drug. So, people who get severe – what we call immunotherapy-related adverse events – may not be able to continue on their drugs. But even that is not necessarily always the case.

Patricia:

This next one really gets to the heart of the doctor-patient relationship. I shouldn’t share my side effects with my healthcare team because I don’t want them to stop my treatment routine.

Dr. Edelman:

Well, you can’t prevent the side effects if you don’t know about them. And I always would tell patients, I said, “You know, if you’re having a problem, please don’t call me at 4:00 on Friday afternoon. I’m gonna end up sending you to the emergency room, which I may anyway.” But a lot of times, we can solve certain things over the phone. There are a lot of side effects that can be treated and particularly if one is aware early on. So, yeah, you should share the side effects because how’s somebody gonna know how to deal with them?

Now, the problem we run into sometimes is in a population that’s on average 60s and 70s, could be younger. There’re lots of things that can be just part of ordinary life. Everybody gets headaches, back pain, etcetera, etcetera.

We have to treat those sometimes and evaluate them much more aggressively because of the possibility of them being related to disease or drug, but it helps to sort it out. You can’t be too blasé about it because sometimes things need to be looked at very urgently, particularly with immunotherapeutic drugs. Some of the side effects that can be severe can sometimes be very subtle in their onset.

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Transcript:

Patricia:

Let’s talk a little bit about health literacy. What would you suggest patients use for online resources? What are good resources?

Dr. Edelman:

So, there are some excellent resources. The International Association for the Study of Lung Cancer has resources for patients. The National Coalition of Comprehensive Cancer Center Network (NCCN) has resources. American Society of Clinical Oncology has resources. So, those or American Cancer Society. So, there are some really reliable sources out there. And there’s a great deal that’s very unreliable – people’s Facebook pages. I’ve seen this.

Patricia:

It’s a big place.

Dr. Edelman:

Everybody always – and I think it’s important for people to understand. There will be people who will get something and have a fantastic response. I’ve used anecdotes.

The anecdotes I’ve used are to illustrate the potential hope of benefit. They’re not exceptions to the rule anymore. They’re the good case scenarios. I could have just as many anecdotes of people who didn’t benefit and stuff. And I think it is important going into this – and that’s why we are reassessing patients constantly and getting repeat scans because we don’t necessarily know always – even if something’s 90 percent effective, it means 10 percent of the time it’s not.

And each patient – we’re getting better at individualizing and personalizing therapy, but we’re not perfect yet. And we probably never will be. So, there will always be anecdotes. I think what’s – as a friend of mine puts it – the plural of anecdotes is not data. When I say, “Well, chemoimmunotherapy works.” It’s not because I have anecdotes of that, though anecdotes illustrate the magnitude of benefit.

I have data that shows that the chemoimmunotherapy regimen was compared to chemotherapy and was clearly and unequivocally superior. When I give a statistic that 60 percent of patients, 65 percent, can benefit from those types of regimens. That’s based upon prospective randomized control trials.

Is Lung Cancer Treatment Effective in Older Patients?

Is Lung Cancer Treatment Effective in Older Patients? from Patient Empowerment Network on Vimeo.

Lung cancer expert Dr. Martin Edelman tackles common misconceptions about the effectiveness of lung cancer treatment in elderly patients. Want to learn more? Download the Program Resource Guide here.

Dr. Martin J. Edelman is Chair of the Department of Hematology/Oncology and Deputy Director for Clinical Research at Fox Chase Cancer Center. More about this expert here.

View more from Fact or Fiction? Lung Cancer


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Transcript:

Patricia:

How about this one? Treatment is not effective in older patients.

Dr. Edelman:

Treatment is highly effective in older patients. It’s interesting. So, we had long arguments about, when I started in this field, whether treatment ever worked, and there were a number of studies that showed that chemotherapy – that one platinum was better – what’s called a platinum-based agent – was better than no therapy.

And then that two drugs were better than one drug. And people would say, “Oh, well, that doesn’t work in the elderly. And they should only get one drug.” And that’s because, I guess, their burning bush on the lawn told them this. And the fact is is that then got evaluated in a controlled trial, a very nicely done study by my European colleagues. But what was crucial was that they used somewhat lower doses of chemotherapy, a little bit different schedule of chemotherapy, and it was clearly superior to a single agent. And those were even days before immunotherapeutics and these targeted agents. So, many patients will benefit. You just have to be aware of certain basic principles in geriatric medicine as well as basic principles of lung cancer care.

So, first off, if the patient is elderly but their tumor is characterized by a driver mutation, they get one of the so-called targeted agents. And these are these days very non-toxic, easy to take, and highly effective.

Patients – many are going to be eligible for immunotherapy either as a single agent or combined with chemotherapy. Chemotherapy drugs could certainly be cut in their doses and still preserve much activity and be done safely.

I had a woman with small cell lung cancer. This is now about a year and a half ago or so. And she’s in her 80s. And she came to me because she was told – oh, just sorta get your affairs in order. And her disease was what we term an extensive small cell. The staging system’s a little bit different, but she didn’t have a really vast bulk of disease. And we treated her with standard chemotherapy drugs but at somewhat lower doses and some careful TLC and some other supportive things like growth factors.

She got all of her treatment on an outpatient basis, had an excellent response. We used radiation later to consolidate her treatment, and I see her back every couple of months. I wouldn’t say that she’s necessarily cured of her disease, but she does yoga every day. She lives a full life. She sees her grandchildren. And she’s, I think – I wanna say 83-84 years old. I think she’s quite grateful for that. It’s not the numerical age.

The flipside is if somebody’s 50 years old and they’re extremely ill when they come in, then one has to be very cautious about what one does. We used to say that those patients who come in who are severely impaired should simply get supportive care and hospice services.

And actually, how would I put it? Our lives have gotten a little bit more difficult lately because as things have gotten better for patients – because I can’t necessarily say that as much because some patients may be very susceptible to the effects of – their disease may be very susceptible to the effects of immunotherapy. I had one patient who was a younger gentleman who was on a gurney. He was in his 50s, lost an enormous amount of weight , he was on oxygen. We immediately gave him fluids. My fellow – I had an excellent fellow at the time – came to me and said, “Should we admit him and send him to hospice? Or just send him to hospice?” And I looked, and he had a biomarker that indicated that he might have an excellent response to immunotherapy, so we gave him solely immunotherapy and saw him back a few days later. He was still pretty touch and go. We gave him some fluids. A week after that – still, we were kinda touch and go, but he was still with us.

And then a week after that my medical assistant, comes in, and she says, “You know, he looks a little bit better today.” And he was in a wheelchair that day. And then a few weeks after that, he had a walker, and a few weeks after that a cane and about a year after that was asking me about whether or not he could go on a cruise. Again, I still see this gentleman – a couple weeks ago. It’s now almost two years later. And the question now that we have is – should we stop his treatment? And he is restored to complete full health, has had almost no side effects of treatment.

So again, this is not every patient. Some people will be treated and get every side effect and no benefit, but I think I’ve become a lot more reluctant to say that any patient should not at least be offered the opportunity for treatment knowing what the potential side effects are. And there still are considerable and sometimes severe side effects from therapy.

Does Surgery Cause Lung Cancer to Spread? The Facts.

Does Surgery Cause Lung Cancer to Spread? The Facts. from Patient Empowerment Network on Vimeo.

Could undergoing surgery cause your lung cancer to spread? Dr. Martin Edelman debunks this misconception.

Dr. Martin J. Edelman is Chair of the Department of Hematology/Oncology and Deputy Director for Clinical Research at Fox Chase Cancer Center. More about this expert here.

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Transcript:

Patricia:

Sure. Here’s one I hadn’t heard until just now. Surgery causes lung cancer to spread.

Dr. Edelman:

Yeah, that’s common in certain states. When I was in Maryland that was a biggie.

So, there’s a myth that the air gets to the tumor, and then it spreads. But that’s certainly not true. It certainly is possible that in a bad surgical procedure that disease can be spread, but I think historically what that was was in the days before we had as accurate of radiographic studies. So, it’s kinda interesting. I always say, “I’m not that old, and I began medical school before there were CT scans.” So, the way you would diagnose something was with a chest x-ray. That was your best chest imaging. And the brain you’d image with something called a pneumoencephalogram, which is – you don’t know what that is. Most people don’t, and they should be thankful for that. But we had no real way of knowing these things. So, what would happen is there would be a surgical exploration. They would say, “Well, it looks very localized.” But then you’d go in, and there was lots of disease all over the place.

And for the most part, that doesn’t happen anymore. Now we have CT/PET scans. We have MRIs. Patients before they go to surgery usually have had – our pulmonary physicians will usually have sampled the nodes in the middle of the chest, the mediastinum. So, it isn’t that there aren’t surprises, but there are far fewer. And certainly, a properly done operation should not spread lung cancer. I would emphasize the properly done operation. It is my strong belief that nobody should have surgery for lung cancer from other than a board certified thoracic surgeon who spends their time thinking about lung cancer, preferably in an institution with a fair volume of this.

We know – it should be no surprise to people, practice makes perfect. People who really focus in an area – people at the NCI-Designated Cancer Centers, comprehensive cancer centers – who do a lot of this have greater expertise.

Lung Cancer Treatment Decisions: Which Path is Best for You?

Lung Cancer Treatment Decisions: Which Path is Best for You? from Patient Empowerment Network on Vimeo.

Dr. Martin Edelman reviews key factors that help to determine a treatment course for lung cancer patients.

Dr. Martin J. Edelman is Chair of the Department of Hematology/Oncology and Deputy Director for Clinical Research at Fox Chase Cancer Center. More about this expert here.

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Transcript:

Patricia:

How are you approaching treatment decisions with your patients?

Dr. Edelman:

Well, the treatment decisions that we make – that I make are those that are in ways similar to other medical oncologists. It really depends because some of the patients may first go to a surgeon or whatever. However they come into the system, there are a few key factors in this. First is – make your decision based upon, Number 1, which kind of lung cancer. So, there are two major varieties. You have small cell and non-small cell, and they are treated – they are biologically distinct, and they are treated in distinct ways.

And then the next major consideration is the stage of the tumor, which is our way of expressing how advanced that is and deciding on both the therapy as well as conveying a prognosis and evaluating a patient for a clinical trial. And that’s based upon the size and location of the tumor; presence, absence, and location of lymph nodes; and the presence or absence and, these days, the number of metastatic areas of disease.

And then, lastly, and again depending a little bit upon the stage and interacting with all the others is what condition is the patient in? Anybody can get lung cancer, but still the median is in older individuals.

Many of these patients have compromised cardiac and pulmonary status as well as other diseases of aging, hypertension, cardiac disease, etcetera. Those people – one obviously has to tailor one’s treatments to fit those comorbidities. So, that’s sort of how the basic assessment – obviously, some patients show up with metastatic disease. We know that, but we go through a whole process for this.

The staging system that we use is complicated, and it keeps changing. We’re, gosh, up to version eight of this? I started with version three. I’m not quite sure I’ve fully mastered the current one, and the ninth edition is coming soon. And why does it keep changing? Because our knowledge of the disease keeps changing. The database keeps expanding.

We’re able to be more refined. Molecular variables have not yet fully entered into our considerations. Unquestionably, they will. But basically, one could consider lung cancer – despite the four major stages and multiple substages – that you really have three buckets that people will fit into. They have localized disease, which we will predominantly address with a localized therapy – surgery, radiation. And many of those patients, however, particularly those who might have a lymph node that’s positive, will benefit from chemotherapy to prevent recurrence.

We have patients with locally advanced disease. Primarily, those are patients who have lymph nodes located in the middle of the chest as opposed to more localized disease where if there’s a lymph node present it’s more in the lobe of the lung. Those patients with lymph nodes in the middle of the chest or larger tumors are approached with frequently a combination of chemotherapy, radiation, sometimes surgery.

And then we have patients with advanced disease who will be predominantly treated with drug therapies, which nowadays, depending upon the molecular background of the tumor, could be a targeted treatment if they have a specific mutation.

Something we see most frequently, though certainly not exclusively, in patients with scant or no smoking history, they may be approached with immunotherapy or chemotherapy combined with immunotherapy.

And there are many considerations that go into those decisions. And even in advanced stage, there are certainly roles for surgery and radiation depending upon whether there are structural abnormalities, occasionally whether there are relatively few areas or several areas of metastatic disease. And in the localized and locally advanced disease, our goal is cure in those, though we certainly are not there for every patient yet.

And in advanced disease, it’s extension of life, which is now quite considerable compared to untreated disease. And I think in certain situations, particularly those who only have a single area of metastatic disease, curative treatment is a realistic possibility. And even those with more disseminated disease, we’re now beginning to see a substantial fraction of patients who are still alive at five years or more. So, we’re beginning very cautiously to think that perhaps some of those patients may even be cured of their disease, though I’m not quite ready to say that.

How Genetic Testing Has Revolutionized Lung Cancer Treatment

How Genetic Testing Has Revolutionized Lung Cancer Treatment from Patient Empowerment Network on Vimeo.

Dr. Martin Edelman explains how genetic testing has revolutionized the lung cancer treatment landscape. Want to learn more? Download the Program Resource Guide here.

Dr. Martin J. Edelman is Chair of the Department of Hematology/Oncology and Deputy Director for Clinical Research at Fox Chase Cancer Center. More about this expert here.

View more from Fact or Fiction? Lung Cancer

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Lung Cancer Treatment Decisions: Which Path is Best for You?

  

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Transcript:

Patricia:

How is genetic testing changing the landscape?

Dr. Edelman:

So, genetic testing – and in this case the testing of the tumor, not the germline, not the individual – has been very, very crucial. If you go back about 20 years ago, there was a family of drugs called epidermal growth factor receptor inhibitors or EGFR inhibitors.

And the basic science at the time made it look like these would be best combined with chemotherapy in squamous cell carcinoma. And as it turned out, combined with chemotherapy they weren’t very useful. But as single agents, there were these occasional very dramatic results.

So, that came at a time when we were able to evaluate tumor DNA, sequence it with some degree of ease at a reasonable cost. So, there was a discovery of specific mutations, which were targeted by these drugs. So, it was sort of interesting in that it was the clinical observation that led to the discoveries in biology, not really the other way around.

But then that in turn resulted in looking for other mutations, which were found, and then the development of other drugs – in some cases, the repurposing of other drugs for those. And now we have about a half a dozen very validated targets, each one of which in a small slice of the population – between say 1 percent and 5 percent – 10 percent of the lung cancer population – but these – if the patient has within their cancer that particular mutation, these are drugs that are 80 percent-plus effective and frequently can be administered with relatively little toxicity.

And usually they’ll give them benefit for one-plus years or more. So, that’s been an example of progress there.

Could Advances in Lung Cancer Research Benefit You?

Could Advances in Lung Cancer Research Benefit You? from Patient Empowerment Network on Vimeo.

Expert Dr. Martin Edelman reviews the latest lung cancer research and explains how it may impact patient care. Want to learn more? Download the Program Resource Guide here.

Dr. Martin J. Edelman is Chair of the Department of Hematology/Oncology and Deputy Director for Clinical Research at Fox Chase Cancer Center. More about this expert here.

View more from Fact or Fiction? Lung Cancer


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Transcript:

Patricia:

Let’s start with an overview of lung cancer’s research. Can you tell us a little bit about the field right now?

Dr. Edelman:

So, I think the field has been remarkable over the last few years. There’s been more progress, more drugs, more things that have happened in the last five years than probably the prior 50. It’s been an amazing time both for developments in microbiology as well as in immunotherapy of the disease, which is exciting for all concerned.

For patient’s, of course – really a promise of longer, better lives, even cures where we previously did not see any in advanced disease. For the scientists – an amazing amount of new information. And for clinicians and clinical investigators – just almost too many questions for us to answer.

Patricia:

It sounds like the field is really advancing quickly. What do you attribute that to?

Dr. Edelman:

Well, you know, I think there are a number of things. Everybody always talks about breakthroughs, but breakthroughs really happen after decades of other work. And what’s happening now is really a result of many, many years of different types of work. There were our colleagues in immunology who built this area of cancer immunology for many years – I have to say with much skepticism from many, myself included.

The advances in molecular biology – our abilities to do things with tumors to determine genetics at a rate and a pace and a cost that was previously unimaginable. All of these things have developed in the last few years but really are a result of the decades of work before that. If you look at immunotherapy – probably one of our biggest areas of progress – the roots of that are a century old. So, nothing’s really new. It’s just now we have the technology and the ability to really use it. And then I would also say that we’ve created the infrastructure that lets us test this – the people who have done the studies, the endpoints for the studies, the expertise in doing clinical trials – that also was there for decades, and we frequently were kind of ridiculed at times.

Oh, you’re just testing this drug against that drug, but the reality is is it was those incremental advances. It was the ability to know the endpoints, to refine the populations, to develop the infrastructure that allowed for all of this to happen.

Patricia:

Dr. Edelman, as a researcher in the field, tell us why you’re hopeful about lung cancer research.

Dr. Edelman:

Well, I think that we have gone from trials with very small incremental improvements and frequently a very slow degree of progress where if we had a positive study every two or three years, we were thrilled – to the point where we’ve had an avalanche of positive studies. I don’t think my younger colleagues know what a negative trial looks like anymore. Even our negative trials are pretty impressive. We’ve had studies where an immunotherapy agent was compared with chemotherapy. And it was designed to show that the drug would be better.

And it was just as good, and that was a negative study. That’s the correct interpretation, but still I would point out that that’s quite remarkable because these other drugs had taken us 25-30 years to develop. And now we have another drug with a very different mechanism of action that’s as good potentially. That’s impressive. I think we’ve just had an amazing degree of progress in the last few years. We have far more drugs. We understand far more about the disease – the technology at every point from diagnosis to assessment of response to the ability to evaluate better what we’re not doing well. So, our studies now frequently have biopsies before, during, and after treatment in a way of trying to figure out why is stuff working or not working.

Back in 2006 or so, I proposed a study. We ended up doing it, but it took two or three years because we were requiring a biopsy result – actually, not even a new biopsy but just an archived specimen from the original biopsy to determine eligibility, and there was strong pushback that we would never be able to do that. And now, we routinely are getting biopsies and re-biopsying, and that’s over a brief period of time.

So, we’re getting to get better understanding of the disease, and why stuff works and doesn’t work. And I think that that’s why our progress will accelerate. And I would again emphasize progress only happens – real progress – only through clinical trials. We’ve cured a lot of mice for many decades. A mouse is not a person. You actually have to do the studies patient by patient, and I think we are making substantial progress. We almost have too many things to test right now.

Fact or Fiction? AML Causes & Symptoms


Dr. Daniel Pollyea, an AML specialist, dispels common myths around the causes and symptoms of AML and shares advice so that you can identify credible resources for information. Download the Program Guide here.

Dr. Daniel A. Pollyea is Clinical Director of Leukemia Services in the Division of Medical Oncology, Hematologic Malignancies and Blood and Marrow Transplant at University of Colorado Cancer Center. 

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Transcript:

Ross:

I’m Ross Reynolds. Today we’re gonna be debunking some common misconceptions about the causes and symptoms of AML.

And joining me is Dr. Daniel Pollyea. Dr. Pollyea, could you introduce yourself?

 

Dr. Pollyea:

Yeah. Hi. Good morning, everyone. I’m Dan Pollyea. I’m an Associate Professor of Medicine here at the University of Colorado, where I am the Clinical Director of Leukemia Service.

 

Ross:

I wanna emphasize to you that this program is not a substitute for medical advice, so be sure to consult your healthcare team when it comes to solid information about it. But you will get some background that I think you’re gonna find useful. And you might have some questions as we go along.

 Dr. Pollyea, let’s start out with the basics. What are the causes of AML?

 

Dr. Pollyea:

Yeah. So, Acute Myeloid Leukemia, it’s a disease, a cancer of the bone marrow.

And it’s the result of an accumulation of mutation and chromosomal abnormalities that affect the DNA of a precursor cell in the bone marrow, otherwise known as a stem cell.

And those abnormalities accumulate until that cell can no longer properly mature, and it also can’t properly die. And so, a cell like that just makes copy after copy after copy of a cell until it crowds out the whole bone marrow with these sorta useless, immature cells.

And the end result of that is the failure of the bone marrow, which causes all of the problems associated with this disease. So, biologically, that’s sort of what happens to make this disease occur.

 

Ross:

What are some of the myths that you hear from patients that come in and they say, “Oh, this must’ve caused my AML,” but you have to tell them that’s not so?

 

Dr. Pollyea:

Right. So, I mean, this is one of the most frustrating issues for patients and their families after diagnosis. I mean, it’s a rare disease, only about 30,000 cases a year in the United States. And so, trying to associate a rare disease with external or environmental factors is difficult to impossible. So, although there are a variety of exposures that probably contribute to this disease, we have very little understanding of what those exposures typically are or how that all works.

So, there’s a few things that we know pretty well; large doses of radiation, either associated with like industrial accidents like the Chernobyl disaster, or some of the radiation therapies that patients receive for other types of cancer. Other types of chemotherapy that are used to cure other cancers can contribute to this disease in later years.

We know that there are certain precursor conditions that can evolve to AML, so a person with myelodysplastic syndrome, for instance, has a fairly high chance of someday evolving to develop Acute Myeloid Leukemia. But beyond these sort of a few associations, there isn’t a whole lot that’s known or proven.

 

Ross:

Now there is radiation associated with X-rays, and some people think that X-rays can cause AML. Is that true?

 

Dr. Pollyea:

Yeah.

So, I mean, I think a priori no because millions of people get X-rays every day, and only 30,000 people a year get AML. So, clearly it’s not a simple association between getting an X-ray and developing AML. But I think that there is an unknown interaction between environmental exposures and a person’s individual genetic makeup that makes a person more or less susceptible to developing something like AML with respect to exposure to the environment or X-rays and things.

So, while you cannot say that getting an X-ray will lead to AML, certainly there are some people who are more sensitive to the damage that’s done by something like an X-ray. And so, the best course of action is to be cautious and judicious about your exposure to these things, but not to not get these things when they are medically necessary.

So, that’s the challenging balance.

 

Ross:

Here’s something else we’ve heard, that weed killers can be a risk factor for AML. Is that true?

 

Dr. Pollyea:

I mean, I think there’s a lot coming out now about weed killers and their association with other types of cancers. Again, I go back to the limitation we have in that in only 30,000 people a year in the United States get AML. Millions of people are exposed to weed killers.

We’re statistically never going to be able to make a clear association. I think that there are certainly some risks for some people. Whether you’re that person who’s more susceptible to developing leukemia or any other cancer because of exposure to a weed killer is impossible to know.

So, like all of these things, I think the advice we have is you have to live your life. You have to do your best to sort of avoid things that you can avoid that you think would be… Or that may cause problems. But not to let those things prevent you from living a normal life.

I know that’s not a satisfying answer, but at the moment that’s the best answer we have.

 

Ross:

Is formaldehyde exposure another risk factor for AML?

 

Dr. Pollyea:

Yeah. We think that it is, and kind of along the lines of benzene. But, again, we think that those studies that have shown those types of association show it in very high amounts, amounts that most people in this country would not be exposed to. But I do think, or we do think that there is something to that, to formaldehyde somehow contributing to this.

 

Ross:

What’s the difference between a risk factor for AML and a cause of AML?

 

Dr. Pollyea:

Yeah. So, I think risk factors by definition are things that may contribute to AML. And a risk factor for AML by that definition could be walking down the street and having some exposure to radiation from the sun. A cause of AML is something that is a much more solid sort of well-understood factor.

Like I said before, having myelodysplastic syndrome, there is a high chance that that can evolve to Acute Myeloid Leukemia. And if that happens then the MDS, the myelodysplastic syndrome, could be considered or would be considered the cause of your AML. So, very, very different in terms of the amount of evidence that goes into making those determinations

 

Ross:

Is there a genetic component to this? Can this run in a family?

 

Dr. Pollyea:

Yeah. So, this is a disease of the genome.

So, I mean, in a lot of respects it is a genetic disease. But the question is very different when you ask is this an inherited genetic disease? Is this disease due to a gene that I inherited from a parent or could pass along to a child?

For many, many years, the answer from the medical community was, “No.” This was not considered to be a disease that clustered in families or that could be inherited. We now know that that’s not necessarily the case. There are some very rare cases where this does seem to travel in families or cluster in families. And we’re now beginning to understand who those people are and what those genes are.

But the vast majority of people with this disease did not inherit a gene to contribute to it and cannot pass this along to a child. This is a random, spontaneous event that occurred within one person’s own body and is not traveling within family. So, we’re learning more and more about this, but really, the vast majority of this is not an inherited genetic condition.

 

Ross:

You’ve mentioned gene mutations. What mutates a gene? What causes that to happen that could lead down the line to AML?

 

Dr. Pollyea:

Yeah. Yeah. That’s a great question. Most of the time we do not know the answer to that. These gene mutations occur spontaneously, randomly, and we don’t understand why they happen when they do happen.

And I know that’s, again, not a satisfying answer. It’s very frustrating, particularly patients come in, and, “I’ve lived a healthy lifestyle. I’ve done everything right. I exercise. I eat right. How could this have happened?”

These are things that for the most part are out of the control of a person. These aren’t impacted by your diet or your activity levels, what you eat or don’t eat, what you do or don’t do. That’s a real frustration. In the end, in almost all cases we don’t know or understand why these gene mutations or these, I call them mistakes in the body, occur when they occur. We don’t understand them.

And, Dr. Pollyea, someone asked if benzene can be a risk factor for AML.

 

Dr. Pollyea:

Yeah. So, benzene is one of the sort of rare environmental exposure associations that we do have clear associations with AML.

But the level of benzene that a person would need to be exposed to is really something that hasn’t been seen in this country in a very long time.

We’d be talking about like an industrial accident type exposure in almost all cases, so being exposed to a cleaning solution or some other fairly minor exposure to benzene, we don’t think is enough, in most cases, to prompt this disease. But benzene in very high doses, like an industrial accident, yes, that is something that we understand can certainly contribute or cause AML.

 

Ross:                          

Autoimmune diseases, such as arthritis, can they increase the risk of AML?

 

Dr. Pollyea:

Oh, boy. That is a really interesting one. So, there are papers in the literature that do support those associations. And I know in my own practice I certainly see that trend. So, I do think that there is something there. There is a proven association between autoimmune conditions and myelodysplastic syndrome, which I said before can be a clear precursor condition to AML. So, certainly, that is an association that is a possibility.

It can be a little difficult to tease out whether it’s those diseases that are associated with ultimately developing AML, or the treatments that people get for some of those autoimmune diseases. Those treatments can modulate the immune system in certain ways that may, in fact, contribute or drive the disease. So, that’s a difficult thing to tease out.

But in general terms, yes, I think there are some associations. Now not by a long shot everyone with an autoimmune disease gets AML. It’s a teeny, tiny fraction. But I think there is an association there.

 

Ross:

How easy is it to diagnose AML?

 

Dr. Pollyea:

Well, I mean, I think there’s very clear diagnostic criteria for AML. But I guess that doesn’t really answer the question. And we certainly have patients who come to us after many months of frustration without a clear diagnosis.

So, those scenarios can play out. Many times AML’s a very dramatic presentation, so people get very, very sick very, very quickly with extraordinarily high white blood cell counts and suppression of all the other blood counts that come from the bone marrow like red blood cells and platelets.

In those cases it’s pretty clear that there is a type of acute leukemia going on. There can be some difficulty distinguishing Acute Myeloid from Acute Lymphoblastic Leukemia; those are sort of like cousins, but very different and treated differently. So, it kinda runs the gamut. I mean, it can be pretty clear, but it’s sometimes missed, so yeah.

 

Ross:

This is a great lead-in to my next question, which is about the symptoms of AML. What should be the warning signs that this might be something you need to get looked at?

 

Dr. Pollyea:

Right. So, at presentation, the main symptoms are reflective of the fact that the bone marrow, the organ that makes all the cells of the blood, has failed.

So, that can cause severe anemia. Signs of anemia: a white sort of appearance, feeling dizzy or lightheaded when standing, short of breath, weak, tired, fatigue. Those are all pretty clear presenting symptoms for AML. Because the bone marrow also is responsible for making platelets that clot the blood, some people will present with a bleeding complication, or a very subtle rash made up of these particular red dots. We call that a petechial rash. And that rash can come on when the platelet count gets very low.

Sometimes a person will present with an infection or infections that don’t go away or don’t clear because of decrease in white blood cells, the infection-fighting cells of the bone marrow. Those are made in the bone marrow and can fail in the setting of this disease. So, those are the most common symptoms at presentation, symptoms that are reflective of bone marrow failure.

 

Ross:

You mentioned that sometimes the presentation could be very dramatic, and it sounds like the symptoms are very severe, very quickly. Is that always the case? Is that often the case?

 

Dr. Pollyea:

That is the case in, I would say, a minority of times. That’s usually the case. It’s more often seen in younger patients with AML. Typically, older patients with AML have a more smoldering course and a much less dramatic presentation, although this sort of very dramatic and dangerous presentation can happen in older patients, but it’s probably something like a third of the time that those very dramatic and medical emergency presentations occur.

 

Ross:

How important is early diagnosis?

 

Dr. Pollyea:

Well, I mean, it’s crucial. I mean, in particular in those cases where it’s a very dramatic and proliferative diagnosis, or presentation. A quick diagnosis and recognition of this condition is very important because the sooner a person starts effective treatment the better the ultimate outcome is.

I would say in general terms that applies to all AML patients, but certainly there’s some degrees of variation. So, there’s some AML patients that when I hear about their case on the phone from a referring doctor, it’s appropriate to see them next week in the clinic.

So, it’s not always a medical emergency, but we would never, even in those next-week-in-the-clinic patients, this isn’t something that can wait for weeks or certainly months. This is something that needs to be addressed fairly quickly.

 

Ross:

What are the best ways to manage those symptoms?

 

Dr. Pollyea:

Right. So, I mean, at presentation, all those symptoms, the best way to manage those are to start treatment as quickly as possible. So, impacting the underlying cause of this disease is the most important and critical factor to getting a person feeling better because all of these problems stem from the disease in the bone marrow, and so everything else that you do to sort of help a person’s symptoms are Band-Aids when you’re not talking about getting to the root cause.

So, that’s at presentation. Now once we start treatment, there are many potential side effects to any number of treatments. And it all is dependent on what treatment you’re getting and other things about you that will make this a significant problem in some cases. And in that setting, we do have ways that we can aggressively manage a person’s side effects.

 

Ross:

Can you manage all of the symptoms? Or can people still be experiencing symptoms even after they’re in treatment?

 

Dr. Pollyea:

Absolutely. So, a person with this disease, depending on how long they’ve had it and some of the features, may not be feeling back to their baseline self for potentially weeks or months after treatment starts in the best-case scenario. So, that can be very frustrating, but a person needs to sort of be able to continue to have a good outlook and stay positive.

Because we are able in many cases to make a big impact on this disease and return a person to their pre-disease quality of life.

 

Ross:

What are some of the myths that you hear, Dr. Pollyea, about the treatment? Some things that people come in to you saying they think that it helps, but there’s no science to back that up?

 

Dr. Pollyea:

So, myths about treatment, so many people have a lot of preconceived notions about the intensity of a therapy that they’re going to be asked to withstand. And although sometimes we do treat this disease very intensively, that’s not always the case, and now we have some very effective lower-intensity regimens that can be used in a variety of different scenarios.

There are a lot of people who have a lot of preconceived notions about a stem-cell transplant or a bone-marrow transplant and whether or not they would be eligible for this based on maybe what they’ve heard from friends or family, or what they’ve seen in the internet.

And those are often incorrect. And so, keeping an open mind about treatment options, and discussing those in detail with your doctor are really, really important.

 

Ross:

You mentioned sometimes it presents in young people, sometimes in older people. What’s sort of typical?

 

Dr. Pollyea:

This is a disease of predominantly older patients, so the median age of presentation is 68. So, that means that over half of the patients are over 68 years old at diagnosis. So, while this does happen, can happen in younger patients, that’s really an unusual situation. This disease is, like I said, it is predominantly a disease of older patients.

 

Ross:

There are some patients who I understand think that supplements can deal with the symptoms of AML. Is that accurate?

 

Dr. Pollyea:

You know, I mean, I think the supplement question is always a challenge. A lot of these supplements, or most of these supplements have never been tested with the rigor of treatments that we’re accustomed to in the medical establishment.

That being said, I won’t deny that some of the supplements can help patients based on what patients’ experiences are and what they tell me. I think what’s really important is just be very open and honest with your doctor about the supplements that you’re taking or want to take to ensure that there are no sort of unanticipated interactions with treatments.

Because I think most doctors are very open to having their patients care for themselves in the ways that they’ve become accustomed to, and they know their bodies very well, and we’re very open to that. But there are sometimes that a drug or a supplement might have a bad interaction with the treatment.

And so, a good example in my practice is antioxidants. So, there’s a lot of literature, a lot of interest in antioxidants as cancer-prevention treatment.

And a lot of that is not well-established, but still I don’t see much harm. But when it comes time to treating a cancer, that’s a very different situation. When we give a patient treatment to try to kill the cancer cells, many times we’re trying to provoke oxidation. That’s part of how these drugs and these treatments work.

So, if you’re taking those treatments, but also at the same time taking antioxidants, there’s the potential you could sort of be cutting your therapy off at the knees, fighting it with one hand behind your back. So, for the period of time when my patients are getting an active treatment, I ask that they don’t take it antioxidant.

And they can resume that in the future in the hopes of preventing another cancer. But the time to prevent with an antioxidant isn’t appropriate when you’re dealing with an active cancer. So, that’s just one example.

 

Ross:

Fatigue could be a symptom of AML, but there are a lot of causes of fatigue.

How do you differentiate between something that really could be AML and something that isn’t?

 

Dr. Pollyea:

Yeah. That’s a challenge because I think these are, as I said, older patients. And older patients have a lot of other medical problems. And older people get fatigued, just that’s unfortunately part of the normal aging process. So, we would usually make an assumption that a person’s fatigue and diagnosis is due to the leukemia, the anemia as a result of the leukemia.

But as we successfully treat a patient if they are responding based on their numbers and other objective criteria, but the fatigue is not improving then I think that’s where we would start to look at other contributing factors, and there can be many, so having an open mind at that point is important.

But at the beginning, this is such a monster of a disease, it’s so overwhelming, I think the focus is usually on assumption that the fatigue is due to the disease or to a treatment associated with this disease.

 

Ross:

This question: is loss of appetite a symptom of AML?

 

Dr. Pollyea:

Yeah. I definitely see that, hear that, so sometimes people come in and they say that. Sometimes it may not be a loss of appetite, but an extreme weight loss, so a lot of different types of cancer, including AML, can cause that, just basically unintentional weight loss.

A person’s not trying to lose weight. They’re eating what they think is their normal amount and they’re losing tremendous amounts of weight. So, those are both potential presenting symptoms with AML. And loss of appetite, unfortunately, can be associated with some of the treatments for this disease. And taste changes, things not tasting good, can all contribute to that as well, so those are all challenges that our patients face.

 

Ross:

How important is to get a second opinion? I mean, are all doctors like you pretty much on the same page when it comes to symptoms and treatment?

 

Dr. Pollyea:

So, this is a challenge. So, the answer to the second question first is unfortunately, no. A lot of this hasn’t quite been standardized. And some doctors, oncologists, cancer doctors, they’ll predominantly be treating the things that are common: colon cancer, breast cancer, prostate cancer. And they will probably only have a few cases of acute leukemia a year.

And so, their approach to this is going to be different than somebody who spends all day seeing patients with AML and thinking about AML.

So, a second opinion is a very nice thing to be able to do. The problem with this disease is that most times it doesn’t afford that opportunity. So, with other conditions you have some time to go out, read about it, talk to some different doctors, get a good plan together.

With AML, often that’s not a possibility. A person is so urgently sick that you have to sorta deal with the resources where you are. The best recommendation I have there, if you do find yourself in a situation where there’s not a lot of expertise is to ask your doctor to just call somebody in the region or email somebody in the region who may have that expertise.

And most doctors all over the country have that sort of resource or partner that they will go to and talk the case through with them, and maybe a transfer to one of those high-volume centers is appropriate.

And maybe that’s not a possibility or appropriate, but maybe you would benefit from just talking… Maybe your doctor would benefit from talking this through. But in cases where it’s not such a dramatic presentation, then yeah, for sure, I think a second opinion can be appropriate. But this isn’t something that can be sort of drawn out for long period of time.

 

Ross:

You know, when you find out something like this, your tendency might be to jump on the web and start searching for AML. How do you vet those sources that you look at? How do you figure out that their – what would be a sign that they’re bogus sources?

 

Dr. Pollyea:

Yeah. I mean, I think this field is so rapidly changing and the treatment that we have, that I would, for the most part, assume that what you’re finding on the web is not relevant and is not an up-to-date resource. So, the resources that I listed, the NCCN, UpToDate, the Leukemia & Lymphoma Society, I should mention.

A very important resource that has up-to-date information, and they have even phone numbers for patients and their families to call to get connected with the proper people in a particular city, so that is a really important resource. But I’d be really, really cautious about what you find on the internet because things are changing so fast in this field. There’s a lot of outdated and misinformation on the internet.

 

Ross:

Well, then there’s outright scams. One of the things you mentioned before we went on is be cautious if someone’s asking you to put money upfront, or if it’s a nonmedical facility. What are some things that people should watch out for?

 

Dr. Pollyea:

Yeah. So, one of the things that is so important in our area is clinical trials and participating in clinical trials. Patients who opt to do this and receive experimental therapies can sometimes get the treatment of the future, get a drug that’s not currently available through the FDA, but may have a lot of promise.

And this is the way that we fight this disease. We’ve recently had an onslaught of approvals for AML and that’s because the patients being willing to participate in sanctioned clinical trials. So, participating in a sanctioned clinical trial is crucial, and it’s always a recommendation of all leukemia doctors.

When you participate in a conventional clinical trial, you’re asked to sign a consent form that explains what you’re doing and why. There is a confirmation that this has been vetted by an institution’s regulatory board that is prioritizing the safety and well-being of you, the patient. This has been approved by the FDA as a clinical trial. Nobody would ever ask you to pay money. That’s not ethical to participate in a clinical trial. Insurance covers whatever standard of care. And the clinical trial covers anything that isn’t.

So, if you find yourself in a situation where you’re not being asked to sign a consent form, where a clinical trial has not been reviewed by a regulatory board, where your doctor is not a leukemia specialist, where the FDA has not sanctioned the treatment, all of those are alarm signs.

Because there are people out there that are preying on patients in a desperate situation, a very difficult time in their life, and giving them sort of false hope and leading them down paths that are not legitimate.

One easy thing to do to sorta check to see if a clinical trial is legitimate is to go onto clinicaltrials.gov.

This is a resource set up by our national healthcare system that now feeds in every legitimate clinical trial from all over the world, needs to be registered on clinicaltrials.gov. So, if you can’t find your clinical trial on clinicaltrials.gov, I would have a lot skepticism and caution about that.

 

Ross:

Like what advice do you have for people when they’re first diagnosed? What are the first things they should try to do?

 

Dr. Pollyea:

Yeah. I mean, that reaction is totally normal and natural. I mean, many times these people are perfectly healthy or have been perfectly healthy, and this news is a complete shock.

And so, it is normal and appropriate to have some period of grieving for the healthy life that you are losing. But I would also, while giving yourself that time to grieve, first, draw on your support system, your family, your friends. Allow them to help you. Accept that assistance that they have. And to be optimistic because we are getting so much better at treating this disease.

I had mentioned before, there has been an onslaught of approvals for drugs in this area the likes of which hasn’t been seen in decades. We have new tools and weapons in our arsenal that we couldn’t have dreamed of even a few years ago.

We in our community are very excited and hopeful about the future and we hope that that will translate ultimately to patients, but being depressed or being down, being scared, all of that is normal.

All of that is expected. Anyone would feel like that. Allowing yourself to have those feelings and emotions is important, as long as it doesn’t get in the way of doing what you need to do to fight this disease.

 

Ross:

It sounds like you’re hopeful about new treatments for the disease. How about a cure? What’s the science? What’s the medical science say about that? Are we getting any closer to that?

 

Dr. Pollyea:

We are getting closer to curing this in more cases. So, like I mentioned before, as bad as this is, we can already cure some subsets of patients. There’s one type of Acute Myeloid Leukemia called Acute Promyelocytic Leukemia, APL. It’s an uncommon form of AML, less than 10 percent.

But we can cure close to 99 percent of people with APL. And APL, 15 years ago, was universally the worst form of acute leukemia to get. So, that dramatic 180 that we’ve seen in APL, we are hoping to translate into other forms of AML.

Some other forms of AML have cure rates as high as 50 percent, 60 percent, 70 percent in the right setting. Sometimes we can cure patients with a stem cell transplant fairly reliably. So, we are very, very hopeful about our ability to continue to make progress and cure more and more and more of these patients. That’s the future that we see.

 

Ross:

Dr. Pollyea, thank you so much. And thank you so much for ending on such a positive note. We really appreciate it. And thank you for joining us for this program today.

To learn more about AML and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Ross Reynolds. Thanks for joining us.