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

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

What do you need to know before deciding which treatment is best for YOUR prostate cancer? Dr. Maha Hussain discusses the role of key tests in choosing therapy, including biomarker testing, provides tips for partnering with your care team and reviews recent research news.

Dr. Maha Hussain is the Deputy Director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Learn more about this expert here.

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See More From INSIST! Prostate Cancer

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How Do Genetic Mutations Impact Prostate Cancer 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 prostate cancer therapy for your individual disease and why it’s essential to insist on key testing. Before we meet our guest, let’s review a few important details. 

The reminder email you received about this program contains a link to program materials. If you haven’t already, click on that link to access information to follow along during this 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.  

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. 

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

Dr. Hussain:

Sure. Thank you, Katherine. 

It’s my pleasure to join you. And to the audience, nice to meet you all virtually. My name is Maha Hussain. I am a genitourinary medical oncologist with a focus on prostate cancer and bladder cancer. And I am a professor at Northwestern University Feinberg School of Medicine, Department of Medicine, and endowed professor there. And I also serve as the deputy director for the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. 

Katherine:

Wonderful. Thank you so much for taking time out of your busy schedule to join us today. 

Dr. Hussain:

My pleasure. 

Katherine:

I’d like to start by asking about developments in prostate cancer research and treatment. Experts recently gathered at the annual American Society of Clinical Oncology meeting, also known as ASCO, to share their research. 

So, what were the highlights from that meeting that you feel patients should know about? 

Dr. Hussain:

I think probably perhaps I can focus on two major – what I would consider major highlights, and those were the results from two randomized Phase III clinical trials. 

One of the trials is called the VISION trial. And the VISION trial was a Phase III randomized trial evaluating lutetium-PSMA-617 treatment in patients with metastatic castration-resistant prostate cancer. And the delightful thing about this study is that that study was positive. The PSMA story has been really going on for a few years now. And there’s the PSMA for purposes of scans, imaging, to assess the cancer. And the FDA just approved a PSMA PET imaging this year. 

I think it was in May when it was approved. And that would help better define if the cancer is spread or not, and it help with the decision regarding treatment. But the second part is treatment purposes, so identifying the cancer location and trying to attack it with a specific sort of targeted attack to the tumor is really important. 

And so, the FDA is currently looking at this particular agent. And I am hopeful that we will hear soon from the FDA, hopefully before the end of the year, and maybe – who knows? – maybe by summer, middle summer or end of summer. Because I do think that would be a major benchmark in there. And so, that’s one thing. 

The other clinical trial that I thought was interesting from a data perspective – and for disclosure, I am one of the investigators on this study. And this was an intergroup Southwest Oncology, or SWOG, sponsored clinical trial. So, it’s a federal study that Dr. Aggarwal presented. And this was a study that was aiming at maximizing, again, the anti-tumor therapy with the use of a drug which I call is the younger brother of abiraterone. 

So, abiraterone is a drug that is FDA-approved and has been around for several years right now for both castration-resistant prostate cancer and certainly hormone-sensitive metastatic disease. And so, TAK 700 (Orteronel) is a younger brother, I call it, of abiraterone. And one of the potential advantageous when this trial was designed was the fact that you don’t need to use prednisone. And the trial was completed. It was a national clinical trial. And what was interesting is that there is certainly what appears to be a potential benefit, but not in terms of the conclusive based on the way the study was designed.

Having said that, what I thought was remarkable is that patients who basically were only on the control arm was LHRH therapy, so this could’ve been like Lupron, Zoladex, or something like that plus bicalutamide, which is what we call combined androgen deprivation. And that was sort of like the strongest control arm we could do at the time when the trial was designed. 

Remarkably, the patients who were on that arm had a median survival of basically 70 months. That’s the median. That’s the bell-shaped curve with the number in the middle. Seventy months is probably the longest ever in any other randomized trials in this disease space, in the hormone sensitive space. So, that tells us is that men are living longer with prostate cancer, even though it’s metastatic disease; and, yes, it’s not necessarily curable, but men are living longer. And it’s a function of all of the better treatments that are supportive care and everything that was going on.  

And so, the control arm, as I mentioned, was the 70.2 months. The actual experimental arm was about 81.1 months. And again, I don’t know where things will go from this. Obviously, I’m not the sponsor not the FDA. But the point here is that men are living longer, and so wellness and health become even more so important than we ever did. And as I tell my patients, every day you’ll live longer. The odds of living longer is there because of better treatments coming on. 

So, to me – not to take too much time from the interview – to me, these were the two highlights: new, approved – I’m sorry, new treatment that I’m hoping will be FDA-approved and, obviously, the fact that men are living longer.  

Katherine:

How can patients keep up to date on the research that’s going on? 

Dr. Hussain:

I’m a bit biased, obviously. I’m a member of ASCO. 

And what I would recommend to my patients is to look at the cancer.net website. The cancer.net is a website that is an ASCO-generated website specifically for patients and families to review. It is vetted. The committees are not run just by physicians, oncologists, a multidisciplinary team, but also patient representative. So, the lingo and the presentation are lay-friendly, I call it, there. 

The other part I would say, the NCI website, and the American Cancer Society, the American Urological Association. I would say there’s a lot of stuff on the media. The difficulty is vetting what is sort of fake, what is not so accurate, or bias versus there. I also think that the NCCN has also some resources for patients. 

And one thing I always tell patients: explore, look, but make sure that you talk to your doctor about the meanings of everything because sometimes it can be not – it could be misleading, I should say, or maybe not very clear on what the implications are. 

Katherine:

Right. One thing that’s a topic on the mind of many people right now is COVID. 

Dr. Hussain:

Yeah. 

Katherine:

Is the COVID vaccination safe and effective for prostate cancer patients? 

Dr. Hussain:

The answer is yes and yes. So, I have to say, by default, I deal mostly with older men. Age brings in other comorbidities. And certainly, while I see all kinds of shades of gray in terms of the disease extent, going all the way from newly diagnosed all the way to end-stage disease, the bulk of the patients I end up seeing tend to have more systemic disease and have other issues going on. And I have to say, surprisingly, less than a handful of my patients had the infection. 

Only one required hospitalization with supportive measure, but not even needed incubation; however, he needed a lot of CPAP and other respiratory support. I’m not aware of any of my patients or my colleague’s patients who deal with prostate cancer that have died from COVID. So, I would say that’s the good news and that we have not seen a big hit in the population that I deal with. 

I also know that I would say 99.9 percent of my patients have opted to be vaccinated, and they have tolerated the vaccine just fine. There’s only one case, which I actually even saw just this week, who had been vaccinated but have a very, very severe end-stage disease with significantly compromised bone morrow, who got infected but hospitalized for a few days and is recovering. 

And so, I would say just by the pool of patients I see, my answers are yes and yes. 

Katherine:

Very good. Thank you. 

Dr. Hussain:

And I would encourage all the audience to go get vaccinated. I myself am vaccinated. And I’ve advised all my family members to be vaccinated, just to clarify that too. 

Katherine:

Good. Good to know. Dr. Hussain, we’re going to spend most of this conversation talking about advanced prostate cancer. But before we move on, would you give us a brief overview of the stages of prostate cancer? 

Dr. Hussain:

Absolutely. So, with any cancer, we count sort of like four stages. But I would say in prostate cancer the biggest thing is when the cancer is newly diagnosed, which could be confined to the prostate or locally advanced, meaning the cancer has gotten outside the capsule of the prostate but still within that pelvic region. 

There is the group of patients who have pelvic lymph nodes at time of diagnosis. And of course, that is the patients who have systemic disease, which would be technically stage four. Now, the systemic disease implies any abnormality that is found on scans that is beyond the public region. So, that could be lymph nodes in the back of the belly. That could be thoracic lymph nodes. That could be neck nodes. That could be lung lesions, of course, or bone, or liver. 

Now, the most common area where the cancer goes to is really – when we talk about metastatic disease – is the bone. And then lymph is another area where the cancer goes to. Prostate cancer that is confined to the prostate is curable in the vast majority of patients. There is a category of men who undergo surgery or radiation, and then their PSA begins to go up afterwards. 

And this is what we call biochemical relapse. And this is a situation where we know that, in all likelihood obviously, especially of the patients who have had their prostate out, that the cancer has spread. With the current imagine, a good chunk of times, we do not find anything because we’re able to pick up PSA that goes from undetectable to 0.2 to 0.3, but there’s not enough cancer to show up on the scans. We’re hoping, obviously, the better scans, the PET Axumin scan, the PSMA scans are going to help us to identify sites of metastases. 

But this is a group of men where if there is no cancer visible and the only thing we’re dealing with is PSA that’s going up, if they’ve had surgery, then there’s room for what we call salvage therapy with radiation and hormonal treatment. The case is a bit different if there’s only just the prostate – if radiation was given previously. And of course, we talked about metastatic disease. 

Katherine:

Yeah. Once someone has been diagnosed, what tests are used to help understand the aggressiveness of their disease and their overall prognosis? 

Dr. Hussain:

Well, I think there is different basic things, as in, what was the extent of the cancer? How did it look under the microscope? And what is the PSA levels? So, these are the general things. There are different sort of genomic panels that the urologist will use to kind of decipher and other things to kind of help with figuring out aggressiveness and things like that. What I would say is this, is a patient who is diagnosed and has a cancer, and at a minimum has what we consider a Gleason 7 prostate cancer – so, that’s the scoring system that is done with the original Gleason score, or the new patterns where it’s talking about intermediate risk to high risk – to me, this is a cancer that needs to be treated. 

And again, that’s all to do with if a person has other comorbidities, they have some other terminal condition that’s a separate story. But talking generically, that would be when we would recommend. And these are the patients that are generally not seen by the medical oncologist. They’re seen by the urologist, and then they can refer them to radiation oncology also for consultation. 

Katherine:

Now that we understand how test results can help inform a patient’s cancer and how it may behave. Let’s discuss how they can affect treatment options for men with advanced disease. First, let’s do a brief review of the treatment types currently available. There’s hormone therapy, right. What else? 

Dr. Hussain:

Perhaps, it’s simpler if we focus on advanced disease, specifically metastatic disease. 

So, if that’s the deal, then the backbone of treatment is hormone treatment. And it really is. We call it hormone, but technically it’s an anti-hormone. What we’re trying to do is shut down the hormonal pathway that stimulate the testes, which is the factory that makes testosterone. So, we are looking at shutting down testosterone production from the testes in order to starve the cancer. 

Now, the male hormone is produced predominantly – somewhere about 95 percent of it is made by the testes, and then there are about 5 percent-ish that comes from other sources. These are, again, male hormones like the adrenal gland and so on. And there was a while ago some research – I want to say from the MD Anderson crowd, but this is two years ago – that suggested also that the tumor may start to make sort of in-house production of male hormone to support itself. 

Now, having said that, again, testes continue to be the source of the majority of the male hormone. And so, historically, the first data that showed benefit was actually by surgically removing the testes, which is what we call orchiectomy or bilateral orchiectomy. And then medications began hitting the market and were evaluated in the late ’80s and then 1990s, beginning with Lupron – which by the way, in the ’80s, it was an injection that the patient had to give themselves every day, which is remarkable. 

But even then, there is a personal preference by patients to go and take injections as opposed to go through surgery with orchiectomy. But still, I would say for some patients it may be an option until it ought to be discussed as an option. Then what we know is this, is because of the potential other sources for the male hormone, the concept of what we call combined androgen depravation was being evaluated. 

And again, this goes back to the ’80s when the first drug was flutamide and then bicalutamide, and there are other drugs that became. And they kind of added a sprinkle, I call it, to survival. But it wasn’t dramatic, huge differences in survival. And so, generally, while we used it, everybody believed in using it. Moving forward, the drugs like abiraterone, enzalutamide, apalutamide are the three hormonal drugs that have demonstrated conclusively really an advantage in terms of prolonging life when added to the Lupron. 

So, what I tell my patients is that, when it comes to hormone treatment there is really no way around it. You can delay it. Some people are exploring for some patients who don’t have a lot of cancer, maybe a couple of areas, maybe just do targeted radiation and then leave the person alone to buy them some treatment-free time. 

And, to me, this is where the discussion that has to happen with the patient. What is the objective? Is the objective to kind of be ahead of the game and maximally treat the cancer with the hope of prolonging life? Or is the objective to delay treatment? And I would tell you that, with these types of conversation, nine out of 10 or 9.5 out of 10 men opt for moving aggressively up front with management. So, that’s that. 

Now, the one thing I should point out, one of the trials that also was a landmark trial in this disease was the study CHAARTED, which was an intergroup clinical trial at the time it was designed, led by ECOG, and the PI was Dr. Chris Sweeney. I was part of the team that worked on the design also of the study. 

And that was a trial that looked at adding docetaxel to hormone therapy, versus hormone therapy alone, to try to see if it adds something. Historically, all the chemotherapies prior to that that were added to hormone treatment for patients with newly diagnosed metastatic disease had not delivered. And docetaxel did. 

However, one thing I should point out, based on that trial – and I don’t want to go into too much details for the sake of time – the patients that seemed to be benefiting were the patients that had more aggressive, more disease in their system. And so, liver metastases, lung metastases spread in the bone at different areas, not like few isolated areas in the spine or the pelvis, but much more than that. 

And so, for the patients who have what we call high-volume prostate cancer based on scans – and I’m happy to explain what that means if it’s needed – these are the patients that I would offer either the docetaxel plus hormone treatment, which is the injection, or the injection plus the hormonal pills that I mentioned earlier. 

Katherine:

What about targeted therapy? How is that used? 

Dr. Hussain:

Okay. So, let’s begin with the molecularly targeted therapy. So, as we speak right now, for patients who have newly diagnosed metastatic disease that we call hormone sensitive, molecularly targeted therapy is not standard of care. So, I would encourage patients who may qualify for clinical trial to be involved in those. The flipside is – we can talk about it – is that molecularly targeted therapies, specifically with PARP inhibitors have pretty much entered in the space of prostate cancer with a couple of drugs that were FDA-approved. 

The other way of targeted treatment, which would be what we refer to targeted radiation, this would be a different story. This is not systemic treatment. This is a local treatment. And what is done is basically if patients do not have a lot of cancer in their body based on scans, and only certain areas, and they are starting systemic therapy, they can certainly consult with a radiation oncologist to target radiation to areas that are visible on scan. So, if somebody has a couple of, let’s say, pelvic bone lesions, maybe a lymph node, and they are already starting systemic therapy, they can consult with a radiation oncologist focal radiation. And so, that would be the general scheme. 

Katherine:

Many patients are confused about the role of genetics and biomarker testing in prostate cancer care. 

For people who haven’t heard of some of these terms before, let’s go into the definitions. So, what is genomic or biomarker testing, first of all?  

Dr. Hussain: So, I think there’s one thing. Maybe I can explain because the wording can be confusing. So, there is the genetics, and there is the genomics. The genetics would be what we inherit from our families. So, this would be present in our body. The genomics testing would be to look for what the structure of the genes of the cancer itself, cancer cells itself. Now, that doesn’t mean that this was inherited. It’s just that this is a renegade, and it evolved. And that is what is going to show up. 

The reason these two are important, both of them have implications potentially for treatment or perhaps clinical trials. And again, with the PARP inhibitors, the BRCA-like genes will have implications for treatment sort of for resistance cancers. 

With regard to the genetics, the implications are for, again, inheritance of family and potential risk for blood relatives. Now, there are panels that are FDA-approved for the purpose of genetic testing. And the requirement or the indications right now, anybody who presents with metastatic disease or an aggressive disease and diagnosis, the recommendation is to proceed with the genetic testing, certainly counseling and testing, because there are some people who prefer not to be tested. And that’s something else. 

What I tell my patients is this, even if the testing is done and it was negative for inherited genes that might put the patient family at potential higher risk, the fact that a person has prostate cancer by default puts potential, adds risks to family, to blood relatives. 

And the risks aren’t just for the males with regard to prostate cancer, but certainly breast cancer, ovarian cancer, pancreatic cancer potentially, and things of that sort. So, this is where I think a patient needs to be discussing with their doctors. And certainly, there are many centers that have genetics counselor, and so that’s where I generally refer my patients to. I counsel them myself, and then refer them also for more discussions with genetics counselor. 

Katherine:

What exactly are genetic mutations? And how do they impact a treatment path? 

Dr. Hussain:

Well, I think, again, it’s the changes that happens in specific genes that may promote the aggressiveness of a cancer. And so, the BRCA gene is one of the oldest genes that have been identified in breast cancer. And essentially, the body regulates itself. 

And when cancer cells come up and they sort of – the body no longer sustains that regulation, the genetic regulation in those cancer cells. Those cancer cells will behave the way they want to. That means that they’re going to grow faster. That means they could be resistant to treatment and things like that. And so, that’s what we check for, these alterations. And there are certain medications that would allow – and again, in prostate cancer, it’s not a lot. It’s just, as I said, right now the only things that are proven is the PARP inhibitors. This is essentially to kinda gang over the cancer cell, preventing from allowing it to repair itself so it can continue to grow. 

Katherine:

Some patients may not know if they’ve received these important tests. So, for patients that aren’t all that sure, what key questions should they be asking their physician or their specialist? 

Dr. Hussain:

So, I would say when it comes to the genetics testing, I believe a patient has to consent. 

Because again, we live in the U.S., and this is a private matter for the patient. So, this generally has to be the case. Otherwise, depending on the institution, sometimes some tests will require for the overall testing for looking for any genetic alterations, general tumor alternation. Different centers have different things. But the patient should ask and say to their doctor, “Have my cancer genes been tested? Have my genes been tested? And if they have, what are the results?” Because we generally share with the patients once it’s been done. 

The other things I should point out, some of the good things that have happened recently. Up until recently, when it comes to the tumor genomic testing, tissue was required. Nowadays, the FDA has approved blood tests that several companies now run that can actually collect blood sample and basically test it for circulating tumor cell genes there. 

Now, no testing is 100 percent perfect. But in situations like patients with prostate cancer who may not have recent tissue or adequate tissue for testing, certainly doing the blood test to verify if there is anything reflective of the genes of the cancer, and that may allow for potential actionable-type treatments. Again, up until now, this is more going to apply for potential clinical trials or resistant metastatic disease. 

Katherine:

Are there other important factors to consider, like a patient’s age, that can help them access the best treatment for their prostate cancer? 

Dr. Hussain:

Yes. And I think that age is one factor. What I say and what I tell my fellows, age is to be respected, but used to discriminate in terms of management. 

 We all age. And certainly, the body reserve is not the same. And so, that’s why I would say that has to be respected. But it doesn’t mean that we cannot treat patients. 

And I’ll tell you, it’s interesting. There are times where you have – I have a gentleman who used to run seven miles a day. He was 87 years old. This was in my days when I used to be in Ann Arbor at University of Michigan. And the gentleman came to me, and he said, “Dr. Hussain, I don’t feel good.” And I said, “Sir, why? What has happened?” “I can’t run like I did before.” And I said, “You’re not running?” “No, I am running. I’m just not able to do seven miles a day. I can do only four miles a day.” I’m like, whoa, that’s about 100% more than I do. 

Now, again, I’m bringing this as an extreme example. But for some of the oral agents, like the Olaparib trial, there were men in there literally late-’80s, early-’90s that were included in the clinical trials. Same thing goes for several of the other trials. 

I do think that functionality is important. So, if somebody comes to you so sick they are in a wheelchair, you really have to be very careful. And again, I’m just using kind of extremes. And so, you have to be careful by what you are able to do. And any time the doctor thinks the odds are going to be more harm than good, this is really where absolutely a situation where the physician needs to be careful about it, and the patient needs to understand it also. At the end of the day, it’s a shared decision. 

Katherine:

Before we close, Dr. Hussain, how do you feel about the future or prostate cancer research, and what would you like patients to know? 

Dr. Hussain:

First, let me say that I would love for the patients to know that they are a partner, a most critical partner in the process.  

That we need to continue the research and investment in research. It is research that will end up curing cancer. Wishful thinking will not do it. And patient volunteering, which I think is remarkable across all cancers. The business I’m in, the way that drug discovery and evolution often happen because patients volunteered. And without testing these new treatments and combinations, we will not be able to get better results.  

And I will tell you that, when I started my training, the median survival for patients with resistant prostate cancer was on the magnitude of about nine months. Now it is three years-plus. Now, you could argue, well, that’s not huge. But that is a huge change because, again, we’re picking up the cancers much earlier. And the patients who had, as I mentioned, metastatic disease, again, the longevity then at the time I was in training, but even afterwards, was give and take in the three years. And now we’re talking six-plus years. 

And so, there’s been tremendous progress. And really partnership with the patients and their families and supportive others is very critical, and investment in research. So, yes, advocate constantly for more investment in research. 

Katherine:

All sounds very promising, Dr. Hussain. Thank you so much for taking the time to join us today. 

Dr. Hussain:

My pleasure. And be well, all of you.  

Katherine:

Thank you. 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 prostate cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us. 

Which Tests Do You Need Before Deciding on a CLL Treatment Path?

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Which Tests Do You Need Before Deciding on a CLL Treatment Path? from Patient Empowerment Network on Vimeo.

Why do you need biomarker testing before deciding on a treatment plan for your CLL? Learn which key tests should occur before treatment begins and how the results may impact your care decisions.

See More From INSIST! CLL


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What CLL Tests Are Essential and How Do Results Impact Treatment and Prognosis?

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What is High-Risk CLL and How Is It Treated?

What Factors Impact CLL Treatment Options?

What Factors Impact CLL Treatment Options?

 

Transcript:

Why do you need biomarker testing before deciding on a treatment plan for chronic lymphocytic leukemia—also known as CLL?

The results may predict how your CLL will behave and could indicate that one type of treatment may be more effective than another.

Biomarker testing—also referred to as risk stratification, genetic, or molecular testing—identifies specific gene mutations, proteins, chromosomal abnormalities and/or other molecular changes that are unique to YOUR CLL. 

These changes are only in the CLL cells and do not affect all the cells in your body.  These are not genetic changes that you inherit or pass on to your children.

Several tests that may help to guide these decisions, include:

  • The FISH test identifies chromosome abnormalities, including high-risk markers like the 17p deletion.
  • Next is testing for IGHV mutational status, which determines whether IGHV is mutated in a patient. Mutated IGHV indicates lower-risk CLL.
  • Then there is the TP53 mutation status test, which looks for mutations in the TP53 gene.

So why do these tests results matter?

One reason they matter is because patients with certain biomarkers may respond better to one treatment approach over another. 

  • For example, patients who are IGHV mutated have a special benefit from chemoimmunotherapy with FCR and could consider this approach. Patients who are IGHV unmutated should not consider FCR.
  • Additionally, patients with deletion 17p or TP53 mutations should never take chemoimmunotherapy, as it results in only a very short-term benefit.

When are these tests administered?

IGHV status typically doesn’t change over time and only needs testing at diagnosis or before your initial treatment.

FISH and TP53 should be repeated before beginning every treatment regimen, as these results may change over the course of the disease.

How can you make sure you have had essential biomarker testing?

  • First, always speak up and ask questions. Remember, you have a voice in YOUR CLL care. Your doctor is expecting you to ask questions and should be able to answer them.
  • Ask your doctor if you have had or will receive biomarker testing—including FISH, IGHV, and TP53–and how the results may impact your care and treatment plan. Be sure to ask for paper or electronic copies of your important test results.
  • And finally, bring a friend or a loved one to your appointments to help you process information and to take notes.

To learn more about your CLL and access tools for self-advocacy, visit powerfulpatients.org/CLL.

What CLL Tests Are Essential and How Do Results Impact Treatment and Prognosis?

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What CLL Tests Are Essential and How Do Results Impact Treatment and Prognosis? from Patient Empowerment Network on Vimeo

Which chronic lymphocytic leukemia (CLL) tests are essential for patients? Dr. Lyndsey Roeker shares details about vital tests for CLL and the influence of results on treatment and prognosis.

Dr. Lyndsey Roeker is a hematologic oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Roeker here.

Download Guide

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What is High-Risk CLL and How Is It Treated?

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How Can I Tell if My CLL Treatment is Effective?


Transcript:

Katherine:                  

What tests are necessary to help understand a patient-specific disease, both at diagnosis and prior to treatment?

Dr. Roeker:                

So, at 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:                 

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

Katherine:                  

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 are 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:                   

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 are 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.

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

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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

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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

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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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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.

Confusing CLL Terms Defined

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Confusing CLL Terms Defined from Patient Empowerment Network on Vimeo.

What is FISH testing? What is IGHV? Physician assistant Danielle Roberts explains the meaning of these often confusing terms and their role in disease monitoring and CLL treatment decisions.

Danielle Roberts is a physician assistant with the Bone Marrow Stem Cell Transplant (BMT) team at Winship Cancer Institute at Emory University. Learn more here.

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Transcript:

Danielle Roberts:    

So, a FISH test is a test from your either blood in your bloodstream or from your bone marrow biopsy. And it stands for florescence in situ hybridization. And this is a highly specific test that looks at the chromosomal changes with CLL. This can be done in the peripheral blood or in the bone marrow.

And it’s important to remember that when we consider genetic testing and CLL, we aren’t talking about inherited genes, but the abnormalities that occur within the CLL itself.

So, an IGHV test is a mutational test that stands for the immunoglobulin heavy-chain variable gene locus. This can also be done in the peripheral blood and the bone marrow biopsy. This test can help us determine treatment options as well as help with determining what high-risk features there are for your particular disease.

So, 17p deletion is the deletion of the long arm of chromosome 17. This can be seen at initial diagnosis or it can be acquired later on in disease progression. So, for all patients this is one of the more important tests that if you’re going to ask your doctor if you’ve had, you should ask at a diagnosis. If you’ve relapsed later on, you should ask again if that mutational status is being observed or checked in your follow-up testing.

17p deletion is something that can be acquired along the course of your disease progression. It is not always seen at initial diagnosis but can be acquired if you are relapsed or refractory. Therefore I recommend that every time you’re having peripheral blood for flow or if you’re having bone marrow biopsies, especially if it’s for treatment planning purposes, you should advocate to your physician team to make sure that this test is being performed as it will drive – or as it can drive treatment decision-making.

Practical Advice for Coping with a CLL Diagnosis: What’s Next?

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Practical Advice for Coping with a CLL Diagnosis: What’s Next? from Patient Empowerment Network on Vimeo.

After receiving a diagnosis of chronic lymphocytic leukemia (CLL), patients can have a variety of concerns. Physician assistant Danielle Roberts shares her top three pieces of practical advice for patients to move forward. 

Danielle Roberts is a physician assistant with the Bone Marrow Stem Cell Transplant (BMT) team at Winship Cancer Institute at Emory University. Learn more here.

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Transcript:

Danielle Roberts:       

My recommendations if I could have three things that I would recommend all patients with CLL do, 1.) It would be to have your financial information kind of in line or know how to find that. Unfortunately, a lot of the medications that we use to treat disease are incredibly expensive. However, there are really good patient assistance programs out there. In order to be able to apply for patient assistance programs you do have to submit your financial information to them. So, I would really suggest that you have access or be able to know where to find that.

I would also really recommend you talk to your family members in so that they understand what’s – where you are with your treatment and what’s going on. As a physician’s assistant, one of the questions I generally get is when they bring in a family member or somebody who has not been along in their journey for their treatment, if they’re asking lots of questions, that was and kind of diagnosis. So, I encourage people to talk about that at the beginning, so everybody understands where they are and what the plan for the future is going to be.

And then the last thing that I always recommend to everybody is to understand that not one treatment is right for everybody. Understand that things are going to change and we’re all going to grow and we’re going to learn with the process. But if you don’t tell your healthcare team what’s going on, we can’t help you. And we say that there is no such thing as a bad question to us. You’re never bothering us. That’s what we’re here for. Rather you tell us, even if it may be something you feel is minor, ahead of time so that we can address it and work towards a solution, if there needs to be one.

How Could Emerging CLL Treatments Impact Your Care?

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How Could Emerging CLL Treatments Impact Your Care? from Patient Empowerment Network on Vimeo.

In the changing world of chronic lymphocytic leukemia (CLL) research, how can emerging treatments impact care for patients? Dr. Jennifer Woyach shares information about targeted therapies, immunotherapy and clinical trials, and explains why she is hopeful about the future of CLL care.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

That’s a good point. Are there emerging treatments patients should know about?

Dr. Woyach:               

Yeah. There are a lot of really exciting things going on in CLL right now. And CLL is a disease that has been completely transformed in the last five to 10 years and is poised to do so again. So, I mentioned these therapies that we use for frontline treatment, and there are clinical trials now combining them together. So, these agents work so well on their own. Are they going to be even better if we add them together?

There are also newer target therapies, different targets that we are finding increasingly important in CLL, as well as a modality called CAR-T cells, which most people have heard of where we take patients’ own T cells, modify them in the lab and then, give them back with a goal of getting those cells engineered to kill CLL cells.

These are all things that are not ready for prime time in CLL yet but are available in clinical trials. And I think one other thing I’d really like to put a plug in for is clinical trials in CLL, because right now we’re at a point where our therapies are really very good. But if people just do those treatments, we are never going to figure out which one is the best or figure out, for specific types of patients, which treatment is the best. And so, I advocate that any of my patients that are eligible for clinical trials should consider them, because that’s how we make progress in the disease from an altruistic sense.

That’s how we make things better for everybody. That’s one way a patient can think about it. But more personally than that, being in a clinical trial gives somebody the opportunity to get a treatment that they otherwise wouldn’t get that might be better than our standard of care therapies.

Katherine:                  

Dr. Woyach, as a researcher in the field, why are you hopeful?

Dr. Woyach:               

I am so hopeful in CLL because there is so much that we’re learning every day about the biology of the disease, about specific mutations and other genetic factors that are important and really can be targeted by new drugs. Paralleling our understanding of the disease, there also are many more techniques to make these targeted therapies that kill cancer cells selectively while sparing normal cells and making our drugs even more tolerable.

And I think both the targeted therapies like this and the potential of combining them, figuring out sequences that are best but then, also these newer modalities where we, actually, get the immune system involved like the CAR-T cells. They’re making CAR NK cells now. And just lots of other strategies that could be used together with targeted therapies to, hopefully, cure the disease.

Targeted CLL Therapy: What Are the Side Effects?

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What are common side effects of chronic lymphocytic leukemia (CLL) targeted therapies? Dr. Jennifer Woyach discusses side effects of specific targeted therapies and the importance of reporting any issues to your doctor for optimal quality of life.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

If there are side effects, what would some of the side effects be for these targeted therapies?

Dr. Woyach:               

So, it depends on the drug. So, BTK inhibitors, specifically, ibrutinib can cause some joint and muscle pain, some rashes, diarrhea, heartburn. Those are things that tend to, if they’re going to happen, usually happen earlier on in treatment and tend to get better over time. It can also cause high blood pressure. It can cause an abnormal heart rhythm called atrial fibrillation.

So, those are things we watch out for with ibrutinib. Acalabrutinib really has all of the same side effects but for many of them, they don’t occur as often. And then, the tradeoff there is ibrutinib is given once a day and acalabrutinib is given twice a day. With venetoclax plus obinutuzumab with that regimen, you get a lot more hematologic toxicity. So, you see more lowering of the good white blood cell count, which is, obviously, a risk for infections. That regimen comes with a risk of something called tumor lysis syndrome, which is where the cells can break down too quickly and cause damage to the kidneys, damage to the heart.

It can also cause some GI disturbance like some diarrhea, nausea, abdominal pain, things like that. I see there are a lot of side effects. And, of course, when I’m talking to a patient about treatment, we go over them in more detail than that. But I think the important thing is with all of these therapies, we do have ways to manage these side effects.

One thing I think is important for patients to remember is your doctor doesn’t know you’re having side effects unless you tell them. So, we know that people have these side effects. But if you don’t tell us that you’re having diarrhea or heartburn or things like that, we can’t help with it. And we have a lot of medicines that can help these things.

 

 

 

 

What Is YOUR Role in CLL Treatment Decisions?

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What is the chronic lymphocytic leukemia (CLL) patient’s role in making treatment decisions? Dr. Jennifer Woyach explains frontline CLL therapies and how patients help guide the treatment decision that’s best for them.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

Dr. Woyach, what do you feel is the patient’s role in this conversation about treatment approaches?

Dr. Woyach:               

I think that, obviously, the patient is the most important part of the talk of treatment indications. Like I mentioned, sometimes we have the discussion of chemotherapy versus a targeted therapy. More often, the discussion is we have three approved frontline CLL therapies right now. We have two BTK inhibitors or Bruton’s tyrosine kinase inhibitors, ibrutinib, acalabrutinib.

And then, we have a BCL-2, venetoclax, that’s given in combination with an antibody called obinutuzumab. These are very different treatments in terms of side effect profiles, how they’re administered, how often they’re administered, just as an example. The BTK inhibitors are pills. And they’re meant to be given indefinitely. So, you start them with plans that you’re not going to stop them, unless the patient doesn’t tolerate them or they stop working. And so, with that type of regimen, you have the kind of burden of being on treatment for a long period of time.

But on the flipside, it’s very easy to start treatment. So, if you decide you want a BTK inhibitor, I write a prescription for it, it comes to your house, you start it. I usually see patients monthly for the first six months and then, we go to every three months. It’s very easy to start treatment.

The other type of treatment, the venetoclax plus with the obinutuzumab regimen, that’s the BCL-2 inhibitor with an antibody, it’s a finite therapy. So, people are treated for a year and then, they go off treatment. The flipside of that is they’re a lot more time intensive in the beginning. So, you have the IV therapy with the obinutuzumab. Venetoclax you, actually, have to ramp up the dose so patients have to come in weekly for the first five weeks, and they have to come in monthly for their infusions. So, it’s much more time intensive up front but then, you get to stop treatment. And so, those are considerations that I can’t answer for somebody.

I don’t know which one people would prefer and people prefer different things. So, we spend a lot of time talking about all of the different scenarios and what’s going to make the therapy work best for the patient.

 

 

 

 

Could CLL Be Inherited?

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Can chronic lymphocytic leukemia (CLL) be inherited directly from parents? Dr. Jennifer Woyach discusses the likelihood of passing down CLL to children and the difference between genetic mutations and acquired mutations in CLL.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

We have another question from a patient who wants to know if their children will inherit CLL. Is there any link between inherited mutations and CLL?

Dr. Woyach:               

That’s a very, very common and really important question. I would say of the hematologic cancers, CLL is one with higher linkage in families, which means that people with CLL are more likely to have another family member with CLL though it’s still not very common.

And it’s very different from breast cancer or the solid tumors where we know that these specific mutations indicate families that are going to have risk of disease. There has actually been a lot of study over the years of families that tend to have multiple people with CLL. Unfortunately, there really have not been genes identified that are the reason for those family linkages. I think there has been only one family that I know of where they’ve actually found a gene that was likely the cause of multiple family members’ illnesses. So, yeah, there is no indication to test family members.

I tell people do not worry that you’re going to pass this to your children or your grandchildren. CLL is not something that we should be using as like a marker of whether you should have kids or should have anything like that.

So, maybe a little more likely in family members but not enough to really be worried about that.

Katherine:                  

What are the differences or difference between inherited and acquired genetic mutations?

Dr. Woyach:              

So, inherited mutations are those that you get from your parents. And there are lots of inherited mutations that, actually, can predispose to cancer. Specifically, I mentioned the TP53 mutation and CLL cells. Well, there are also people who inherit a TP53  mutation have risk factors for multiple cancers. And CLL, specifically, every mutation that we talk about is an acquired mutation. So, that’s also known as a somatic mutation. So, they’re mutations in the cancer cells. But if you did DNA sequencing of the normal cells, they would not be there.

What Does It Mean to Have High-Risk CLL?

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What Does It Mean to Have High-Risk CLL? from Patient Empowerment Network on Vimeo.

What does high-risk chronic lymphocytic leukemia (CLL) mean exactly? Dr. Jennifer Woyach explains the meaning of high-risk CLL, factors in determining disease progression, and the impact on treatment decisions.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

We have a patient question. I have 17p deletion. Should I be worried?

Dr. Woyach:               

So, 17p deletion is usually associated with more aggressive disease biology almost always associated with that unmutated IGHV. The reason I bring that up is there are a very small subset of patients who have 17p deletion and mutated IGHV who, actually, have pretty indolent or slow growing disease.

People who don’t, which is the majority of them with 17p deletion, do have a shortened time to treatment and shortened survival with most of our current therapies. There have been a lot of advances though in the treatment of 17p deleted CLL. And may of our newer therapies can very much prolong the remission time in the lives of patients with 17p deletion.

Katherine:                  

Dr. Woyach, how do these chromosomal changes affect disease progression and prognosis?

Dr. Woyach:               

So, the markers that are associated with more aggressive disease biology usually are going to be associated with people that need treatment within the first few years after diagnosis, especially those people who have 17p deletion, 11q deletion, unmutated IGHV.

Katherine:                  

What exactly are prognostic factors? Would you define that?

Dr. Woyach:               

Sure. Prognostic factors, and I mentioned three of them, the IGHV, FISH, and the TP53 mutation, are ones that have been studied extensively and shown that the presence of this marker or some change in this marker is associated with a change in the biology of the disease or in the response to therapy.

Katherine:                  

How does the identification of these changes or mutations affect treatment options?

Dr. Woyach:               

Well, right now, we’re lucky in CLL because we have a lot of treatment options. I would say the most important changes when we’re talking about somebody with CLL that is about to start their first treatment is the decision of whether chemotherapy is ever appropriate. So, almost everybody with CLL now is treated exclusively with targeted therapies.                              

So, nonchemotherapeutic options. There are some people who are young, and in CLL terms that means under the age of 65, who have mutated IGHV and who otherwise have good genetic list disease. So, normal chromosomes of the 13q deletion, no TP53 mutation. That small subset of patients, actually, has the potential to be cured with a specific type of chemotherapy. It’s called FCR or fludarabine, cyclophosphamide, rituximab. So, for those young, healthy patients, it’s really important to know those risk factors to know if they are in that group that has that potential for cure.

The converse to that is if patients don’t fall in that group, they probably shouldn’t receive chemotherapy as their first treatment, because it’s not as effective as our other therapies.

Katherine:                  

Yeah. It makes sense.

Dr. Woyach:               

And then, even in the future with first and other treatments with novel therapies, we know that patients with 17p deletion and TP53 mutation tend to have a shorter response time. And so, what I use that for in my practice is I know that those are people that I really have to be sure that we’re following them closely, taking any signs of progression seriously, and always have a back-up plan for what we’re going to do if this treatment doesn’t work.

What Tests Should CLL Patients Insist They Receive?

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Which chronic lymphocytic leukemia (CLL) tests are most critical in CLL care? Dr. Jennnifer Woyach details the key tests, what the tests identify, and how they help provide optimal care personalized to each patient.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

The goal of this program, Dr. Woyach, is to provide the confidence and tools for patients to advocate for the essential tests to get the best care personalized to them. Are there specific tests that patients should make sure they have?

Dr. Woyach:               

Yeah. In CLL, I would say there are three that are very, very important before starting treatment. The first is something called the IGHV mutational status.

What that is defined as is the changes in the variable region of the immunoglobulin heavy chain. That’s a big mouthful that doesn’t mean a lot to most people. So, I’ll give you just a little background on what that really means biologically and then, what that means clinically. So, every B lymphocyte, so a normal B lymphocyte and a CLL cell, has receptors on the surface of the cell that allow it to interact with the environment. And in a normal B lymphocyte, this is really important for the immune system. So, bacteria, virus, something is in the body and the B cell surface receptor is going to be able to recognize that that’s not supposed to be there and then, do something about it.

In CLL, the surface receptors don’t do a lot of interacting with the outside environment but they’re still present there. And in a normal B cell development, the B cells are initially formed in the bone marrow.

And at the time that they’re formed, every one of those receptors is exactly the same. So, we can do DNA sequencing on those receptors and you’ll see that every one is identical. So, during a normal development of a B cell, it undergoes this process that’s called somatic hypermutation, which is where those receptors mutate or change. And that’s important because then, they can recognize different things. And so, you end up with this whole repertoire of thousands or millions of B cells that all are a little bit different and can recognize something different.

So, CLL cells, they’re all clonally related to each other. They’re all going to have the same receptor on their surface. And about 60 percent of the time that receptor is different than the newly born B cells. And so, this is probably a little bit more simplistic than it actually is. But the way we think about that is that those B cells or those CLL cells, which we call mutated because they underwent that mutational process, we think that that means that they come from a more mature initiating cell.

And they tend to be less aggressive, more slow growing. The other 40 percent of patients, if you look at the receptor on their surface, it’s exactly the same as the new B cells in the bone marrow. And we call those IGHV unmutated because they haven’t done that mutational process. And they behave very differently. So, in mutated CLL, only about half of people will ever need therapy in their lives. An average time from diagnosis to first treatment is about 10 years. In contrast to those patients who have unmutated IGHV, basically, all of those people will need therapy at some point in their lives. And average time from diagnosis to first treatment is about three years.

So, you can see how it really breaks people up into two very different categories of disease.

So, that’s the first test and one that’s really important. That’s also one that doesn’t change during the course of the disease. So, if somebody is diagnosed with mutated CLL, it’s always mutated. So, the next marker that’s important is, actually, chromosome changes. So, we know that there are a few different recurrent chromosome abnormalities in CLL that are common and important prognostically. So, one of these is a deletion of part of chromosome 13. It’s called a 13q deletion. It indicates, again, very slow-growing CLL. Patients how have normal chromosomes also are very good disease biology.

Some people have an extra copy of chromosome 12. That’s called trisomy 12, and that’s an intermediate marker. And then, there are two markers that are associated with a little bit more aggressive CLL. One is a deletion of proto chromosome 11. That’s called an 11q deletion.

And the other one is a deletion of proto chromosome 17 called a 17p deletion. These are all abnormalities that are important to test for. And the way that we test for these is something called FISH testing. And FISH stands for fluorescence in situ hybridization. And it’s a way to use an antibody to look for specific abnormalities in the CLL cells. So, that’s important. And another thing that can be done at specialized centers is something called stimulated cytogenetics. So, I mentioned to you with FISH testing, we’re looking for specific abnormalities with antibodies. But the things that we don’t test for we’re not going to see.

So, if they have a chromosome change that we don’t have an antibody looking at, we’ll never detect it. And we know that patients with CLL who have what’s called a complex karyotype, which is three or more chromosome abnormalities, they also have more aggressive disease.

So, like I said, at specialized centers, we can do what’s called a stimulated karyotype, which is where we look at all of the chromosomes. So, that’s FISH testing and karyotype. And then, the last thing is, actually, doing DNA sequencing for a specific mutation called a TP53 mutation. And TP53 is an important tumor suppressor protein. And it is mutated quite commonly in CLL. About 8 to 10 percent of patients at the time of first treatment and, actually, up to about 40 percent of people later on in the course of the disease. Most of the time, we see TP53 mutations occur at the same time as 17p deletions. About 80 percent of the time, those occur together but they can occur on their own.

So, that’s the third test that’s often helpful, especially prior to starting treatment.

Katherine:                  

Do patients need to be retested over time?

Dr. Woyach:               

Yeah. So, for the TP53 mutation and for FISH, it’s important to test for those before each line of therapy. Because those are so important in indicating disease biology and, specifically, with the 17p deletion and TP53 mutation, those indicate patients that are likely to not have as good of a response to treatment. It’s always important to check for those prior to therapy.

What Should You Know About CLL Genetic Testing?

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What Should You Know About CLL Genetic Testing? from Patient Empowerment Network on Vimeo.

In chronic lymphocytic leukemia (CLL) diagnosis and disease management, genetic testing plays a key role. Dr. Jennifer Woyach explains what is examined in CLL genetic testing, the timing and administration of testing, and testing advances.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

Before we get deeper into our conversation about genetics, there are a few terms that patients are often confused by. As a primer, I thought we could start by defining some of these terms. First, what is genetic or molecular testing?

Dr. Woyach:               

So, all cancer cells will have a collection of mutations or abnormalities in the DNA that either make the cell a cancer cell or make it behave in a certain way. And so, these mutations are referred to as the genetic abnormalities of the CLL cells. So, when we talk about genetic testing in CLL, we use it to mean a number of things. We can use it to look specifically for types of mutations so types of genetic abnormalities.

 We also sometimes use that as a kind of catch-all term like genetic or molecular testing also to refer to looking at changes in the chromosomes inside of a CLL cell. That’s also called cytogenetic testing. And then, we also use a number of tests in CLL where we look at specific, not necessarily abnormalities, but just changes in the cell that can indicate a certain type of behavior.

Katherine:                

How is this different from genomic testing?

Dr. Woyach:               

So, genetic and genomic testing, I think, are usually used interchangeably. But sometimes, we use them in different contexts but they really mean the same thing in this case.

Katherine:                  

Okay. And what is a chromosome change?

Dr. Woyach:              

So, as you might remember from biology class maybe a long time ago, as it was for me, inside a cell, so a normal cell or a cancer cell, you have the nucleus, which holds the DNA.

And the DNA is organized into chromosomes. And so, when a cell goes through division, it takes those chromosomes, copies them and then, breaks them apart into two different cells. So, changes can happen in the level of the DNA itself. So, a mutation where one base is changed to something different. So, that would be just like a single nucleotide change. And that’s something you’re not going to see as a change to a chromosome. Another thing that can happen in CLL and in other cancers, too, is that during that process of cell division, an entire chromosome could be duplicated. It could be absent.

More commonly, parts of chromosomes can change. This is all because cancer cells just do a very poor job of editing their division.

An in normal cells, there are multiple steps along the way from the process of copying the genes to copying the chromosomes to doing the division. And every step along the way, if something happens incorrectly, which happens a lot, the cell usually just dies. But a cancer cell is not going to do that because it has so many signals that keep telling it to stay alive that it can tolerate a lot of different abnormalities. And so, you end up with cells that are just very different from what you would see normally.

Katherine:                  

All right. Well, that’s a great way for us to start. Let’s go into the discussion of the relationship between testing and CLL. How is testing administered?

Dr. Woyach:               

So, almost all testing, in terms of molecular genomic testing in CLL, can be done on a blood sample. So, that’s one important thing.

The CLL guidelines recommend that testing for certain prognostic factors be done before the administration of therapy. So, at the very least, before somebody starts treatment, they should have these tests performed. In my practice and I think most CLL specialists find it really helpful to do these tests, not necessarily just at the time of treatment but really at the time of diagnosis or the time we first see the patient because CLL is a very heterogenous disease, which means that it behaves very differently in different people. So, there are some people that are diagnosed and will go 10 or 20 years before they need any treatment.

And many don’t need treatment at all. Whereas other people are very likely to need treatment within the first few years after diagnosis. Some of the genetic tests that we do can help counsel patients on where they’re likely to fall in that spectrum.

And so, I think that’s helpful for people to know early on in the disease course. But really, the tests can be performed at any time before treatment

Katherine:              

Have there been advances in testing?

Dr. Woyach:               

Absolutely. I think in every cancer, we’ve learned so much more about the biology of the disease, specific mutations that cause specific behaviors of cells, and really much more in CLL about the common genetic changes and what those means to response to therapy.

What Is CLL and How Is It Diagnosed?

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What exactly is chronic lymphocytic leukemia (CLL), and what factors help determine a diagnosis? Dr. Jennifer Woyach explains how CLL originates and transforms, the tests involved in diagnosis, and shares a common misconception about CLL.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

Well, Dr. Woyach, let’s start by understanding CLL. Would you briefly walk us through what CLL actually is?

Dr. Woyach:               

Sure. CLL is a cancer of the blood, the lymph nodes, and the bone marrow.

And it happens when a particular type of white blood cell called a B lymphocyte acquires genetic mutations and transforms into a cancer cell. And then, over time, those cancer cells continue to grow and divide. And they can cause symptoms such as enlarged lymph nodes if the cells get stuck in the lymph nodes and continue to grow there. It can cause a high white blood cell count, which usually doesn’t cause any symptoms but is one of the things that we see often in CLL. And then, it can also cause the bone marrow to not be able to produce normal cells because it can get so infiltrated or so full of CLL cells.

And this can cause things like anemia, which is lowering of the red blood cell count and thrombocytopenia, which is lowering of your platelet count.

Katherine:                  

What are the steps involved in reaching a diagnosis?

Dr. Woyach:               

CLL is an interesting disease because it’s one of the only cancers that does not require a biopsy of something for a diagnosis.

So, we can, actually, make the diagnosis of CLL based on the peripheral blood. So, just a blood draw in somebody’s doctor’s office. Usually, CLL is diagnosed in the asymptomatic stage. So, somebody goes to their primary care doctor, has blood drawn usually for another reason, and is found to have a high white blood cell count or sometimes even a fairly normal white blood cell count but a high percentage of lymphocytes. That certain type of cancerous white blood cell. So, the next step in the diagnosis then is something called peripheral blood flow cytometry, which is a specialized test where we look at the markers or antigens on the surface of white blood cells.

So, there is kind of a code of these markers on the surface of all of your blood cells that can tell what type of cells they are. So, for CLL in particular, we’ll see that the cells express some of the normal markers we would see on a normal B lymphocyte.

Things like CD19, CD20, CD23. But they also express a marker called CD5, which is found on normal T lymphocytes but shouldn’t be found on B lymphocytes.

And so, this collection of surface markers can make the diagnosis of CLL. Sometimes, we do need to do extra studies like a bone marrow biopsy or a lymph node biopsy. But often times, those are not necessary at the time of diagnosis.

Katherine:                  

When you meet with patients, Dr. Woyach, what are some common misconceptions that you hear about?

Dr. Woyach:               

I think the biggest thing that I hear, and granted I see a lot of patients after they’ve been diagnosed by someone, gone to see an oncologist and then, come to me after, but one of the common things that I hear is that somebody has told them along the way that they have the good type of cancer, which I think is not a very helpful thing to hear as a patient because, of course, no cancer is a good type of cancer.

I think it’s important to note that CLL is one that has a lot of treatment options and usually extended survival. But I think that’s one of the most common misconceptions that I hear.