Chronic Lymphocytic Leukemia Archives

Chronic lymphocytic leukemia (CLL) is a typically slow-growing cancer which begins in lymphocytes in the bone marrow and extends into the blood. It can also spread to lymph nodes and organs such as the liver and spleen.

CLL develops when too many abnormal lymphocytes grow, crowding out normal blood cells and making it difficult for the body to fight infection.

More resources for Chronic Lymphocytic Leukemia (CLL)  from Patient Empowerment Network.

CLL Treatment: Finding the Best Option for YOU

CLL Treatment: Finding the Best Option for YOU from Patient Empowerment Network on Vimeo.

How could genetic testing results impact your chronic lymphocytic leukemia (CLL) treatment options and overall care? Dr. Jennifer Woyach discusses essential molecular testing and provides tools for self-advocacy and decision making.

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:                  

Welcome to Insist CLL, a program focused on empowering chronic lymphocytic leukemia patients to take an active role and insist on better care. Today, we’ll discuss the latest advances in CLL, including the role of genetic testing and how this may affect treatment options. I’m Katherine Banwell, your host for today’s program. Joining me is Dr. Jennifer Woyach. Welcome. Would you please introduce yourself?

Dr. Woyach:               

Sure. My name is Jennifer Woyach. I’m a CLL specialist from the Ohio State University.

Katherine:                  

Thank you. A reminder, this program is not a substitute for seeking medical advice. Please refer to your own healthcare team. 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 grant it 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.

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.

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% 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% 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 eight to ten percent of patients at the time of first treatment and, actually, up to about forty 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% 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.

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.

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.

Katherine:                  

We have a question from a patient. If I have FCR, does that rule out me using a targeted therapy later on?

Dr. Woyach:               

Absolutely not. And, actually, all of the studies of the targeted therapies, all of the early studies were done in people who previously had had chemotherapy. Most of them had received FCR. So, certainly, receiving chemotherapy doesn’t mean that you can’t get a targeted therapy later on.

Katherine:                  

What are other factors that are important to consider when deciding on a treatment route?

Dr. Woyach:               

So, besides the genetic factors we talked about, other things are age and very closely related to age is fitness status. So, how active is somebody? How able are they to do all of their normal activities? Are there other health problems that we need to be concerned about when thinking of treatment?

As well, certain medications can influence treatment choices, specifically, with oral therapies where there might be drug interactions. And then, also a lot of the decision of frontline therapy is patient preference right now. So, do people prefer to have a time limited therapy? Do they prefer to have an indefinite therapy? Do they prefer an all p.o. regimen or a mix of p.o. and IV? So, there are definitely a lot of considerations when thinking about frontline treatment.

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 effects, [inaudible] [00:28:13] 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 upfront 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.

Katherine:                  

How can patients stay informed about CLL?

Dr. Woyach:               

There is a lot of good information about CLL that’s available online through The Leukemia & Lymphoma Society.

They have a number of resources for lots of different cancers, including CLL. There are a number of different patient centered websites. One is called the CLL Society. There are others that are heavily moderated, provide a lot of good information, and tend to stay on topic with CLL current developments and don’t get into the weeds too much I would say.

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, heart burn. 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 heart burn or things like that, we can’t help with it. And we have a lot of medicines that can help these things.

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 ten 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.

Katherine:                  

Thank you for taking the time to join us today and sharing all of this information with the patients. We appreciate it.

Dr. Woyach:               

Of course. It’s my pleasure.

Katherine:                  

Please take a moment to fill out our survey. It helps us as we plan upcoming programs. And thank you to all of our partners. To learn more about CLL and to access tools to help you become a proactive patient, visit Powerfulpatients.org. I’m Katherine Banwell.

Telemedicine Challenges and Opportunities for CLL Patients

Telemedicine Challenges and Opportunities for CLL Patients from Patient Empowerment Network on Vimeo.

For chronic lymphocytic leukemia patients, some challenges have emerged with care via telemedicine. In this telemEDucation program, CLL expert Dr. John Pagel explains opportunities for patients and providers to optimize these visits.

See More From the CLL TelemEDucation Empowerment Resource Center

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What CLL Population Will Benefit Most From Telemedicine?

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Will Telemedicine Be Part of Routine Management for CLL?

 

Transcript:

 Stephanie: 
Let’s highlight both the challenges and opportunities that come with telemedicine. So first, it does seem to be reshaping the traditional CLL doctor-patient relationship to some extent, and you’ve touched on this. So with your experience as a CLL expert, what are the limitations of telemedicine?

Dr. John Pagel: 
Well, one of the, of course, things about telemedicine is it’s not just figuring out how to do it from the provider’s standpoint, but it’s also figuring out how to do it from the patient’s standpoint. So we can’t expect, to be honest, that this goes just like it would if you were in the clinic, sitting on the exam table with your physician there at the computer right next to you in that exam room, it shouldn’t be expected that it’s going to go like that. And unfortunately, to this point, we’re trying to figure out that. It doesn’t do that. And so that takes some alteration in our approach, on the provider’s side and on the patient’s side as well – and in particular, what the expectations are for these patients and for the providers.

So it needs to be very focused, and it needs to be concise. So what is my message there? For the patient’s side, know that the doctor’s busy, they’re doing their work all day long with lots of sick people potentially, and so they need to be very focused on what the issues are and the direction of the conversation. So come prepared to a telemedicine visit, if you’re a patient. Come prepared to know what you want to talk about and what the focus is with the priorities that you might have that are issues for you around your CLL disease. And the provider will do that hopefully as well. It’s a learning thing. But I will tell you, the first time will take a little bit of learning. By the second, third time that you’re actually interacting with your doctor, that same one-on-one relationship, it really

Will Telemedicine Mitigate Financial Toxicity for CLL Patients?

Will Telemedicine Mitigate Financial Toxicity for CLL Patients? from Patient Empowerment Network on Vimeo.

The cost of chronic lymphocytic leukemia (CLL) care can be inappropriately high for some patients. Watch as CLL expert Dr. John Pagel details how telemedicine can affect the high cost of care.

See More From the CLL TelemEDucation Empowerment Resource Center

Related Resources:

 

What CLL Population Will Benefit Most From Telemedicine?

How Will Telemedicine Impact Time-Limited Therapy in CLL?

Will Telemedicine Be Part of Routine Management for CLL?

 

Transcript:

Stephanie: 
Dr. Pagel, we know the stresses of paying for cancer treatment. So how can maybe telemedicine help to mitigate financial toxicity for these countless CLL patients and their families?

Dr. John Pagel: 
Well, this is an important part of medicine in general, and it’s certainly relevant, of course to the CLL patients. The cost of care is inappropriately high, not just the pharmaceutical agents, but, of course, the visits. So there are evolving ways of figuring out how reimbursement will happen for physicians and how payments happen on the side of patients. We’re still not completely clear on that, but likely what will happen, over time, is that we will be doing less and less unnecessary tests. And with less unnecessary tests, the cost of care will go down for the individual specific community and patients. It’ll be very important for us to figure out what we really need to be doing and what we don’t, and telemedicine’s going to help us figure that out. 

Is Remote Monitoring for CLL Patients on CAR T Therapy the Future?

Is Remote Monitoring for CLL Patients on CAR T Therapy the Future? from Patient Empowerment Network on Vimeo.

Will telemedicine play a greater role in CAR T remote monitoring and help some CLL patients avoid long hospital stays? Learn how harnessing technology could optimize care for CAR T patients.

See More From the CLL TelemEDucation Empowerment Resource Center

Related Resources:

 

What CLL Population Will Benefit Most From Telemedicine?

How Will Telemedicine Impact Time-Limited Therapy in CLL?

Will Telemedicine Be Part of Routine Management for CLL?

 

Transcript:

Stephanie: 

There’s excitement around telemedicine and CAR T, so specifically remotely monitoring CAR T to help avoid patients having to deal with long hospital stays. Is this the future?

Dr. John Pagel: 

It’s clearly the future. So what you’re alluding to, of course, is a way that we are now doing to trick a patient’s own immune system cells into targeting and fighting the cancer, and of course, we’re talking about CLL here. It’s a revolutionary treatment in CLL, we still have quite a ways to go, we are doing a lot of important trials and advancing the field, but we don’t have an approved approach in CLL yet, but we will. No doubt. And the goal of that therapy is not just to eradicate the disease and keep it from coming back, but it’s also to do it in a very safe and actually appropriate way, and that’s as an outpatient.

Those patients clearly have risk for an adverse event or a side effect, that can be problematic. So they have to be in close contact with a physician and sometimes they’re required to be very close to the treating center for prolonged periods of time. Most of the time that’s very uneventful. So it’s a major disruption to a patient’s life. You could imagine that you’re traveling hundreds of miles to go to a center, and not just go to a center that provides the CAR T-cell therapy, but is actually monitoring you for a month or more, so you’re away from home for a long time, living in a hotel, that’s a problem.

Telemedicine is a way to get around that. We will evolve to being able to treat patients, get them home, and then telemedicine will work where the visits can be done in a very expeditious manner, and again, in a very appropriate way so that that will also reduce the interactions away from home, and as we said cost of care as well. 

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Which CLL Treatment Approach Could be Right for You?

Which CLL Treatment Approach Could be Right for You? from Patient Empowerment Network on Vimeo.

Which CLL treatment approach might be best for your individual disease? This animated video walks through important considerations that help guide treatment decisions, including genetic testing results, lifestyle factors and patient preference. 

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CLL Treatment Decisions: What Path is Best for YOU?

 How to Be A Partner in Your CLL Care  Key CLL Treatment Decision-Making Factors

Transcript:

Hi, I’m Christy. I’m a nurse practitioner and I specialize in chronic lymphocytic leukemia, or CLL. With a variety of available treatment options, CLL patients often wonder which approach might be best for their individual disease.

Before we walk through the information that goes into choosing a treatment approach, I want to remind you that this video is intended to help educate CLL patients and their loved ones and shouldn’t be a replacement for advice from your doctor.

So, how is a treatment path determined?

CLL physicians will typically consider several key factors to help guide the decision.

When many CLL patients are first diagnosed, their medical team may use an approach called “watch and wait” or “active surveillance.” This means that treatment won’t begin immediately. Their healthcare team will monitor their CLL via in-person visits and lab testing. And, some patients may never even need treatment, depending on their individual situation.

But, if bloodwork indicates advanced disease, enlarged, bothersome lymph nodes develop, or, if symptoms like fatigue and night sweats are negatively affecting a patient’s daily life, then it may be time to treat the CLL.

Physicians typically consider a patient’s age, overall health, and existing conditions before they suggest an approach. There are also several tests on the CLL cells that may help guide treatment decisions.

Physicians use immune globulin heavy chain gene, also known as IGHV, mutational analysis to determine whether a patient is IGHV mutated or unmutated.

In IGHV mutation analysis testing, being “mutated” is a favorable finding. 

If a patient’s IGHV status is mutated, and, depending on other factors such as age and overall health, the physician may recommend a treatment called FCR. FCR stands for the drugs used in this approach, which are two chemotherapy drugs combined with a targeted treatment that is a monoclonal antibody.  

However, it is important to realize that due to side effects and other risks, chemotherapy is not for everybody. Non-chemotherapy treatments work very well for IGHV mutated patients as well as unmutated patients.

If a patient has unmutated IGHV, then a targeted treatment or a clinical trial might be more effective.

Molecular testing, also known as genetic testing, can identify specific genes, proteins, chromosome changes, and other factors unique to your CLL.

The results can provide your healthcare team with information related to prognosis, risk and which therapy may be most effective in treating your disease.  

One of the most widely used tests is call a FISH test and it looks for specific changes in the chromosomes of your CLL cells.  These specific changes can help understand how well certain treatments are likely to work for you. 

For example, patients with the chromosome abnormality “17p deletion” may have higher-risk disease and will not respond well to chemotherapies such as FCR. An oral targeted treatment approach or a clinical trial will be more effective in patients with 17p deletion.

There are several types of targeted treatments that are currently approved to treat CLL including:

  • Monoclonal Antibodies, which work by targeting specific proteins on cancer cells.
  • And, Kinase Inhibitors, which work by blocking proteins that tell the cancer cell to grow and survive.
  • A combination of treatment approaches may also be considered.

Before you start any treatment, it’s essential to ask your doctor if you have had relevant CLL genetic testing, including FISH testing, and what the results could mean for you.

Finally, one of the most important factors that your healthcare team will consider is YOUR treatment goals. 

It’s very important to consider a treatment’s course and potential side effects.

With the many options available today to treat CLL, you will be able to get effective treatment. How your treatment choice affects your other health conditions and your lifestyle is essential.

Remember, you are a partner in your care and have an active voice in finding the best treatment for you.

When treatment is discussed may be a good time to consider a second opinion or a consult with a specialist.  If you don’t feel supported or an active member of your team, then it is always best to get another opinion if you are able.

So, how can you put this information to work for you and help improve your care?

  • Talk to your physician about what you’ve learned.
  • Ask about testing mentioned in this video and whether you need to be retested over time.
  • Discuss clinical trials with your physician.
  • Visit credible resources to stay up to date on CLL information.

Visit powerfulpatients.org/cll to learn more about CLL.

The Power of Journaling During Cancer Treatment

There are two ways to fight cancer, both of which are equally as important. The first is physical and the second mental. Journaling might not be able to help with the physical symptoms, but easing the mind can truly help in such situations.

By providing a safe place to store your thoughts and experiences, you will be able to find a great source of power. If you have never thought about journaling before, this might be the perfect time for you to give it a try. Here are some important reasons why this might be a very great decision.

1. Keeping track of all important moments

Some people believe that battling cancer is only filled with negative moments and experiences. While that is true to a big extent, there can be plenty of memorable moments that you might want to keep track of. The beginning of your treatments is a moment that you can write about and think about when this situation is over.

Other important moments might include family gatherings, important presents you might receive, very bad and very good days that stand out in your treatment course. Just because a day way difficult doesn’t mean it should be considered bad. At the end of this difficult journey, you will be able to look back at everything you wrote and remember the good and bad times.

2. Helping ease certain symptoms

Another great reason why journaling can truly help cancer patients during their treatments is because of symptom management. Research has actually shown that journaling can help with combating symptoms and dealing with the physical size of things.

Writing about how you feel and what you are going through can help you sleep better and feel more energetic. Getting plenty of rest will allow you to feel less nauseous, be in a better mood and battle everything with a stronger will. The more you face your symptoms, the stronger you will feel through your treatment.

3. Fighting against the stress

The stress that can be caused by such a difficult diagnosis is great and can truly affect your mood and outlook on life. Being under stress can make you feel tired, mess up your sleeping schedule and make you feel more negative about everything. This is not ideal for any situation you are in in your life and there are ways to overcome it.

Journaling can provide you with a safe space to write everything you have in your mind. During your treatments, you will possibly want to appear strong in front of your family and you might not want to share everything you feel. You can write all your thoughts in your journal and let everything out. This way you will be able to handle everything you face and feel a lot less stressed.

4. Reminding yourself of things you love

When dealing with any hardship in life, it is important to keep thinking of things that bring you joy. Journaling has helped me create a notebook full of memories, which I can go through any time I need some positivity in my life. You don’t only have to put words into it but anything and everything that makes you think of memories and people you hold dear.

In your journal you can keep stickers, receipts, drawings and cards from loved ones. Then you can write how receiving these things made you felt. When the days get difficult and you are struggling, open your journal again. Read through everything nice you have collected and it can help you remember all the reasons why this difficult process is worth it.

5. Seeing all the progress you have made

Last but not least, another important reason why journaling is so helpful during cancer treatment is that it can help keep track of your progress. There are going to be many days that will be hard and many that will be good and filled with hope. In order to be able to go through both, it is important that you keep track of everything new that happens in your journey.

The good days will help you remember that things will get better. The difficult days will allow you to live in the moment and work on staying positive. Journaling this experience can also help your family better understand what goes on in your head and how they can help. After you have successfully put this difficult period of your life behind, you can even share your story with other patients through your journal.

Battling cancer every way possible

Journaling is a creative and fun activity that can help you deal with certain symptoms and negative thoughts during your treatment. Even if you have little experience with writing, journaling gives you the chance to get creative. You don’t need any special skills in order to journal. You just need a notebook, some fun colors and a few thoughts in your head.

Through writing about your experiences, you will be able to express how you feel and let everything run its course. This treatment course might be tough, but writing everything down will help you see just how much progress you are making. This can truly help you feel stronger mentally and physically and overcome this situation like a true warrior!

What Subset of CLL Patients Should Utilize Telemedicine?

What Subset of CLL Patients Should Utilize Telemedicine? from Patient Empowerment Network on Vimeo.

With monitoring of chronic lymphocytic leukemia (CLL), there is a subset of patients that will get the most benefit from telemedicine visits. Learn more about which CLL patients should use telemedicine and which higher risk patients should still visit in-person. 

See More From the CLL TelemEDucation Empowerment Resource Center

Related Resources:

 

What CLL Population Will Benefit Most From Telemedicine?

How Will Telemedicine Impact Time-Limited Therapy in CLL?

Will Telemedicine Be Part of Routine Management for CLL?

 

Transcript:

Stephanie Chuang: 

Can you share the telemedicine platforms that you, in your practice, use and maybe so far, what are some of the best practices observed?

Dr. John Pagel: 

Right, and I think that’s probably the biggest key and takeaway that we can talk about here for the audience, is to remember that telemedicine isn’t going to be appropriate for every patient. And for each individual patient, there are times where it certainly would be very appropriate and other times where it might not be. So, you know, of course, people that have active, growing, rapidly progressing disease, we’re not talking about those people, those people need to be seen by their provider, they need, of course, close attention and monitoring. But many, many patients, in fact, the majority of patients with CLL are not in that kind of group.

So we’re talking about people that don’t have high-risk genetic features, in particular, those are things like a deletion of the short arm of chromosome 17, that’s a 17p deletion, or an 11q deletion or a TP53 aberration, those are genetic risks that your doctor will know about with regard to your specific individual CLL. And most people, fortunately don’t have those features and they behave in a very indolent, slow growing, more benign-like fashion, and then those are the people where probably telemedicine would be appropriate for many visits.

I’ll just say, I would suggest that in general, telemedicine shouldn’t be something that you do with every single visit. Every once in a while, you should have that face-to-face, hands-on interaction with your primary provider. But I’ll also remind people that not everyone lives real close to their oncologist or even their CLL expert. So if you’re far away, you can connect not just with your oncologist who takes care of you, but with an expert who might be some distance away, and that’s the beauty I hear about the telemedicine.

Will Telemedicine Be Part of Routine Management for CLL?

Will Telemedicine Be Part of Routine Management for CLL? from Patient Empowerment Network on Vimeo.

With the COVID-19 health crisis, telemedicine has emerged as part of routine healthcare. Watch as CLL expert Dr. John Pagel gives his viewpoint on how telemedicine will be included in routine management of CLL. 

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What CLL Population Will Benefit Most From Telemedicine?

How Will Telemedicine Impact Time-Limited Therapy in CLL?

What Subset of CLL Patients Should Utilize Telemedicine?

 

Transcript:

Stephanie: 

You know, of course, COVID-19 has forced healthcare providers to use telemedicine more than ever before, so do you think this will definitely continue on past COVID-19? And if so, how quickly it will even grow?

Dr. John Pagel: 

Well, I think the federal government’s understanding that this is a part of medicine moving forward that’s important for patients, patients like it, and I don’t blame them. If I’m on that side of care, I feel perfectly fine, I have CLL, let’s say, and nothing’s going on with me, and I’m very well-educated about my disease, and by the way, that’s probably critically important to this whole conversation is to understand and be educated well about your specific disease.

Remember, each patient has to be their own best advocate. And that makes telemedicine work. And frankly, the horse is out of the barn, in my opinion, telemedicine is where we’re going, and it’s not going to come back. Patients like it, physicians are getting used to it, Stephanie, it’s something that we are reluctantly in some ways adopting, but it’s just how it is, and I think it’s going to be a major important thing for many, many CLL patients as routine management. 

How Will Telemedicine Impact Time-Limited Therapy in CLL?

How Will Telemedicine Impact Time-Limited Therapy in CLL? from Patient Empowerment Network on Vimeo.

With chronic lymphocytic leukemia time-limited therapy, treatment is delivered for a pre-determined period of time and then is stopped after remission is achieved. Learn how telemedicine impacts patients on this type of treatment. 

See More From the CLL TelemEDucation Empowerment Resource Center

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What CLL Population Will Benefit Most From Telemedicine?

Will Telemedicine Be Part of Routine Management for CLL?

What Subset of CLL Patients Should Utilize Telemedicine?

 

Transcript:

Stephanie: 

Dr. Pagel, we’d love to ask about the time-limited therapy in CLL specifically, and how telemedicine might play a role in that?

 

Dr. John Pagel: 

Well, this is one of the things that we’re still learning about, Stephanie, and I think it’s going to evolve and change a bit over time, but we know that we need to do. Continually better for patients, of course, we need to meet unmet needs in CLL. And there are lots of unmet needs still in CLL, of course, one of them is curing the disease, and we’re not focusing on therapeutics today in our discussion about working towards that goal, but that does remain a major goal, and we’re working towards that. But really, of course, there are situations with unmet needs where people have been getting therapy continuously now for long, indefinite periods of time, and they may not need all that therapy. And so one of the things is that we’re learning about is what you mentioned time-limited therapy. So the idea of delivering therapy for some defined period of time, getting to a very good remission and then stopping therapy. And where telemedicine comes into play there, is that if they’re off of therapy and doing well, we don’t need to necessarily drag those patients back to the clinic and put them through, not only all of that exposure and that risk, but of course the anxiety that goes with it and everything else.

So again, I think that in those cases where we’re monitoring patients with telemedicine, it’s beautiful for time-limited therapy, and it also allows for us to stay even in closer contact with our patients who again, might have some difficulty getting into the clinic. 

What CLL Population Will Benefit Most From Telemedicine?

What CLL Population Will Benefit Most From Telemedicine? from Patient Empowerment Network on Vimeo.

Among chronic lymphocytic leukemia patients (CLL), there are some that will benefit more from telemedicine visits that have become common practice during the coronavirus crisis. Watch as respected CLL expert Dr. John Pagel explains.

See More From the CLL TelemEDucation Empowerment Resource Center

Related Resources:

 

How Will Telemedicine Impact Time-Limited Therapy in CLL?

Will Telemedicine Be Part of Routine Management for CLL?

What Subset of CLL Patients Should Utilize Telemedicine?

 

Transcript:

Stephanie: 
Now the pandemic has, of course, presented both challenges and opportunities for clinicians who are trying to manage diverse health conditions, and of course, we’re not just talking about COVID-19. So on the positive side, Dr. Pagel, what are the opportunities you see for CLL patients using telemedicine?

Dr. John Pagel: 
Well, you’re right, Stephanie, it isn’t just about COVID, but COVID has certainly changed the landscape of how we approach many patients in 2020 and now in the future moving forward and particularly with regards to telemedicine. And that’s particularly relevant to CLL patients in particular. CLL, remember is a chronic disease, it’s of course, part of the name chronic lymphocytic leukemia, and people will live with this disease for many, many years, perhaps even decades, and often not even be getting therapy but still have, of course, the disease.

And they need to be monitored, and they are commonly monitored with what we call active surveillance. And active surveillance is typically, as the audience well knows, periodic evaluations with physical examinations and perhaps even some laboratory blood work that’s done on an associated visit. And because of the need for those things over the last many years of how we follow people, with active surveillance, people. We have seen frequently in the clinic, and perhaps in some ways they’ve been seen when they perhaps could be evaluated and taken care of in a different way, and that’s where telemedicine comes in for select appropriate CLL patients. Where maybe we don’t need to bring them in to see their provider, they can get labs done perhaps locally at their primary care physician’s office, if the labs need to be done. And often the physical exam can be even done by video or — so by showing the provider what might be going on, and lots of times that physical exam may not even be important.

What do I mean by that? We’ll remember, there are lots of times where even if you have a lymph node or two around, we’re not going to actually institute or change treatment. So there’s a very unique important population of people with CLL who could obviously benefit from telemedicine moving forward. 

Guide: How Can You Access the Latest CLL Treatment Options?

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How Can You Access the Latest CLL Treatment Options?

How Can You Access the Latest CLL Treatment Options? from Patient Empowerment Network on Vimeo.

Could a new or emerging chronic lymphocytic leukemia (CLL) treatment be right for you? In this 30-minute webinar, Dr. Anthony Mato will review current and emerging CLL treatment approaches, important decision-making considerations, and the ins and outs of clinical trials.

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Should You Discuss a CLL Clinical Trial with Your Doctor?

 How to Be A Partner in Your CLL Care  Key CLL Treatment Decision-Making Factors

Transcript:

Katherine:                  

Hello, and welcome to the webinar. I’m Katherine Banwell, your host for today’s program.

Today we’re going to explore promising CLL research and what I could mean for you. Joining me is Dr. Anthony Mato. Welcome, Dr. Mato.                

Would you please introduce yourselves?

Dr. Mato:                   

Hi, I’m Anthony Mato, Director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York.

Katherine:                  

Great. 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. Well, Dr. Mato, when it comes to CLL treatment there seems to be an abundance of new and developing options which, of course, is a great problem to have. To help patients understand more about the types of treatment currently available, let’s review the treatment classes and discuss how they work to fight CLL.

Well, and let’s start with chemo. Some patients are probably familiar with the term FCR. What does that stand for, and how does work?

Dr. Mato:                   

Sure. FCR is a name for three chemotherapies that are combined together.

So, this is fludarabine, cyclophosphamide which are two cytotoxic chemotherapies combined with the monoclonal anti-CD20 antibody rituximab, so two traditional chemos plus an immunotherapy called rituximab that have worked together synergistically and have been quite effective over a prolonged people of time for treating patients with CLL. FCR was originally developed at MD Anderson.

But a very important CLL trial called CLL8 confirmed that FC plus rituximab was better than FC by itself, so a trial that demonstrated improvement in progression-free survival but also in overall survival advantage. And so, this became the standard of care more than a decade, and it has been a very common chemotherapy combination for patients.

Katherine:                  

What about monoclonal antibodies? How do these treat CLL?

Dr. Mato:                   

Great question. So, right now, we have several monoclonal antibodies that are approved in CLL.

They all target the same cell surface marker called CD20. And so, the way antibodies work in general in these patients, in our patients is that we identify a cell surface marker. In this case, it’s the protein CD20, and these antibodies are able to target that specific cell surface marker, bind to it, and in a way act as a flag for the immune system to destroy these cells.

So, an antibody like rituximab may be able to destroy a cell directly, or it may flag the cell to be destroyed within the immune system within the spleen, for example. So, different mechanisms of action but it’s a targeted therapy because it focuses on a specific protein that’s largely expressed on the cancer cells relative to other cells within the body.

Katherine:                  

There are also a variety of inhibitor treatments. What are they, and what exactly are they inhibiting?

Dr. Mato:                   

Yeah, so the kinase inhibitors are probably some of the most important drugs developed for CLL to date.

And we have different classes. One group would be BTK inhibitors which stands for Bruton tyrosine kinase, another would be PI3K inhibitors. Another class would be a BCL-2 inhibitor which is a little bit different. Essentially, the way to think about inhibitors are that they identify key molecules within a cell that are very important for either cell survival or cell signaling. These are the molecules that tell cells to either migrate or to hone in on a particular area or to amplify signaling to allow them to survive.

So, a drug like ibrutinib or acalabrutinib which are BTK inhibitors block this BTK signal and interrupts a very important survival signal in the cell, kinda causes it to go haywire in many ways, and then allows those cells to slowly die over time. PI3K inhibitors like idelalisib or duvelisib do the same. They block a very important and parallel signaling pathway to BTK that cause a very similar effect.

And then venetoclax which is a BCL-2 inhibitor works a little bit differently. So, CLL cells are very primed to actually die except that there are signals in place that block that process called apoptosis, and so venetoclax blocks the blocker of that signal, sort of inhibits the inhibitor to cell death and allows that natural process of cell death to occur in CLL cells.

And so, they’re kinda targeting different pathways, but they’re able to stop the cell in a way. This is very different than cytotoxic chemotherapy like the FC which targets all dividing cells. Here we’re targeting cells where those particular enzymes are most important.

Katherine:                  

Do inhibitors need to be taken indefinitely?

Dr. Mato:                   

That’s a great question, and that’s something that we’re still working out. Right now, BTK inhibitors and PI3K inhibitors are all given as continuous therapies. That’s not to say that they couldn’t be stopped, but they haven’t been studied in a way that allows us to stop them. So, there’s not a lot of evidence to support that.

BCL-2 inhibitors, venetoclax, were studied as either as continuous therapies or as what we call a time-limited therapy, either 12 months in the frontline or 24 months in the relapsed/refractory setting. And so, they can be given for a fixed-duration period and then stopped.

Katherine:                  

Are there combination approaches that are effective?

Dr. Mato:                   

Depends on what you mean as a combination, so right now, BTK inhibitors, ibrutinib, for example, is approved either to be given by itself or with CD20 antibodies, either rituximab or obinutuzumab, another antibody that’s like rituximab in the frontline setting. So, that is a combination of drug plus antibody.

Acalabrutinib is either approved to be given by itself or with the CD20 antibody obinutuzumab. In either case, whether the antibody is present or not, the drug is given continuously. Venetoclax is given either by itself or with a CD20 antibody either obinutuzumab in the frontline setting or rituximab in the relapsed/refractory setting.

There are no approved combinations of kinase inhibitor and kinase inhibitor together or inhibitor/inhibitor. So, there are studies that are exciting about ibrutinib plus venetoclax for example, but there is no one who should be receiving those combinations as a standard of care at this time.

Katherine:                  

Are there any other approaches that we haven’t discussed?

Dr. Mato:                   

Yeah, well, there are other exciting approaches from the spectrum of very experimental to closer-to-market for patients. So, there are other PI3K inhibitors that are in development which may or may not have better toxicity profiles from the current ones. There are noncovalent BTK inhibitors. These are drugs that work like ibrutinib or acalabrutinib, but they may actually overcome resistance to those molecules. So, you’re on ibrutinib; you’re progressing. You develop a resistance mutation. There are drugs that are being studied that might be able to overcome that and recapture the response.

And then there are drugs like CAR-T cells or cellular therapies, using your immune system, actually, genetically engineering your own immune system outside the body to be focused on killing CLL and then putting it back inside the body through a transfusion to allow it to fight cancer more effectively. So, those are some of the more up-and-coming strategies that are closer to being available for patients at this time.

Katherine:                  

All right, and we’ll discuss more about that later on. So, with all of these options, how do you then decide which class might be right for an individual patient?

Dr. Mato:                   

Well, you think about the patient. You think about their medical history, their comorbidities, their preferences, and then you try to focus on their disease biology, their genetic factors, their molecular factors, and also what therapies they’ve had. So, if I had a patient who had ibrutinib previously, I’m not going to give them acalabrutinib if they were resistant, for example. So, it’s not just one thing. It’s multiple things that have to be taken into account in order to make a decision.

And of course, for me as an oncologist, the hardest part is that there have not been many trials comparing the newest therapies to one another. So, I can’t tell you what’s better ibrutinib or acalabrutinib by a head-to-head comparison. I can’t tell you whether you should start with ibrutinib before venetoclax or venetoclax before ibrutinib not because we’re not very interested in having those studies performed. But they have not been performed at this point in time.

The only thing I can tell you based on prospective data from a head-to-head comparison is that we do have direct data comparing acalabrutinib which is a BTK inhibitor to idelalisib in the relapsed/refractory setting. And by all measures, acalabrutinib was better tolerated and more effective. So, we have some very early head-to-head data but not as much as we need in order to make these decisions for patients.

Katherine:

How are side effects taken into consideration?

Dr. Mato:                   

Well, all of these drugs although they are targeted, and they’re oral, and they’re relatively easy compared to chemotherapy are not without side effects. And so, each of these classes have their own unique side effects. BTK inhibitors can be associated with increased bleeding risk or atrial fibrillation or infection. PI3K inhibitors can be associated with lung or liver or colon damage. BCL-2 inhibitors might be associated with lowering of the blood counts and infection risk or something called tumor lysis syndrome.

So, we try to, if you had a side effect to one, not pick a drug with the exact same side effect profile, for example. And we also think about medical history for patients. So, if I had a patient who was on blood thinners and has poorly-controlled atrial arrhythmia like AFib, I might not start them on a BTK inhibitor. If I patient who has active Crohn’s disease or ulcerative colitis that’s poorly controlled, I might not start them on a PI3K inhibitor. And if I have a patient who’s near dialysis because of chronic kidney disease, and I’m worried about further tumor lysis syndrome, I might not start them on a BCL-2 inhibitor.

So, you kinda weigh a patient’s medical history, their prior therapies, and their response and toxicities, and then make a decision on what’s the best fit for patients.

Katherine:                  

Well, what kind of testing is involved to make sure you have the best approach?

Dr. Mato:                   

Well, there’s several tests that we think about using or we do use, and they’re mostly genetic and prognostic tests. And so, what we like to do is look at the CLL cells beyond looking at them under a microscope to try to identify the genetic markers that drive the biology of CLL. So, for example, if I have a patient who has deletion 17p which is one of the more feared chromosome abnormalities, I know right off the bat chemotherapy’s not a good fit for that patient. But I can do quite well with a BTK inhibitor like ibrutinib.

So, we’re starting to use the molecular features of the disease in order to pick therapies that are the best fit for patients. So, we have a board panel at our center that we use. At this point, some of the information isn’t helpful yet.

But some of the information is quite helpful in to make a decision about the best therapy for patients. So, this is truly what we call targeted therapies for individual patients or personalized or individualized approaches based on the disease itself.

Katherine:                  

Dr. Mato, we have some questions from the audience. Let’s start with this one. How high does the white blood count have to be in order to start treatment, and which are the best treatments available at this time?

Dr. Mato:                   

That’s a great question, and it’s a common question we hear in the clinic. So, there is no white blood cell count that defines the need to start therapy. Some patients are treated with relatively low white blood cell count. Some are treated with very high white blood cell counts.

What defines the need for treatment or therapy for CLL are the symptoms of the disease, extreme fatigue, soaking night sweats, fevers that are unexplained by infection, the need for transfusion, bleeding, bruising, growing lymph nodes, growing spleen causing symptoms, frequent infections.

Those are the things that define the need for therapy. A rising white blood cell count by itself or a cutoff at some arbitrary number should never be a reason to start treatment without some of those other factors.

Katherine:                  

Here’s another question for you. How do you monitor to see if a treatment is working, and what if the patient doesn’t respond to any of the treatments?

Dr. Mato:                   

Yeah, so, we response criteria, and so, they’re largely very simple measures. We perform a physical examination before and after treatment to see if the lymph nodes and spleen are decreasing in size. We measure the white blood cell count to verify that it’s going down. We look for normal parameters of normal functioning bone marrow like improvement in the hemoglobin or the platelet count.

So, those are some of the measures we use, and we put them together. And of course, just asking a patient how do they feel, do they feel better, are the symptoms that were associated with the CLL improving, and if the answer is yes, that would be considered responding disease. We also sometimes do measures like CAT scans to measure internal masses or internal lymph nodes and a bone marrow biopsy to verify that all the CLL cells are gone.

So, that’s the basics of a response assessment, and we also venture now into a new territory called MRD or minimal residual disease where we’ll be able to look beyond the traditional response assessment. Sometimes, it measures at a measurement of one in a million cells to verify that there’s no evidence of CLL present. If a therapy’s not working, fortunately – well, first I’ll say that with the modern therapies that we’ve already mentioned, response rates exceeded 90%.

So, it very, very infrequent that we have a patient where we pick the appropriate therapy where it doesn’t work for them. But if one is not working, then we do have measurements of resistance, and we can try to tell why a therapy maybe not working and switch them to an alternate class. And oftentimes, that will solve the problem.

Katherine:                  

Dr. Mato, you mentioned the term MRD. What does that mean?

Dr. Mato:                   

It stands for minimal residual disease. That’s using technology like flow cytometry or PCR or sequencing to take a deep look in the bone marrow and the blood for the presence or absence of CLL.

So, when I perform a bone marrow biopsy, a pathologist with their eyes might count one hundred cells. With MRD testing we could look at 10,000 or 100,000 or 1,000,000 cells to see if there’s any CLL present, much more than the human eye or the human brain could process.

Katherine:                  

Well, this leads us to our next topic, Dr. Mato, and that is emerging treatments for CLL. For people who don’t understand how treatment approvals work, which would you give us an overview of the stages of clinical trials?

Dr. Mato:                   

Sure. I’m very involved in clinical trials at my center. There are different phases of clinical trials. And so, the way that I think about them would be – let’s focus on phase one thru three because those are probably the most relevant ones for patients. The purpose of a Phase One trial is really to define the dose of the drug and confirm that it’s safe or not. We get very, very preliminary data about activity of the drug, but the major question that’s being asked is, “Is this drug safe?”

Phase Two is – and I should also add that Phase One trials are relatively small. So, it’s a small number of patients where we’re trying to find the right dose. By the time we get to Phase Two, we know the drug is likely safe. We have a lot of information about its side effect profile. We might have a hint that it’s active. And so, the purpose of a Phase Two trial is to expand the size of the trial, have more patients recruited, get more information about safety but then get more information about activity.

Of course, there’s no comparator generally in a Phase Two trial. So, it’s not like I’m asking this drug versus another drug. And the end of a Phase Two trial, we know the drug is active, we know it’s safe. And if it appears to be active, we’re feeling confident that it may be better than a standard of care which leads to Phase Three where the drug is compared directly in oftentimes what we call a randomized study to a standard of care.

So, the trial that I mentioned earlier, FCR versus FC would be a great example of a randomized, controlled trial where a new therapy would, in that case, the FCR, was compared to the old therapy, the FC.

In the more modern era, there have been several trials. I example I might mention is the RESONATE trial where ibrutinib was compared head-to-head to an antibody called ofatumumab. Patients who were enrolled were either randomized by a coin flip through a computer to one arm or the other. And then those arms are compared directly to help define a standard of care.

So, that’s kinda the basics of clinical trials, and at our center and many centers around the country, we participate in Phase One, Two, and Three trials trying to ask different questions that are important to our patients.

Katherine:                  

Well, speaking of patients, they’re very often fearful of participating in a clinical trial. What do you say to them to make them feel more comfortable with the idea?

Dr. Mato:                   

I mean, I think the most important thing to highlight is all of the standards of care that we’re using today, ibrutinib, acalabrutinib, idelalisib, duvelisib, venetoclax, these were all just drugs a few years ago that were studied in the context of clinical trials.

And so, our current standards of care are very new on the scene from clinical research. It’s very important to have a conversation with your doctor about the intent of a particular clinical trial. I think most patients are fearful of placebos or blinding where they don’t know what they’re getting, or it’s possible that they’re not getting any treatment at all.

In oncology and particularly CLL, the chances of a clinical trial having a placebo or blinding are very low. We very rarely ever participate in such studies. And so, that should provide reassurance to the patient that they know what they’re getting, they know their dose, their oncologist knows what they’re getting, and oftentimes, many clinical trials have mechanisms called crossover built into them. Meaning, that if you’re getting A versus B, and you get B, and it doesn’t work, you often have opportunity to crossover to A.

Clinical trials in CLL are the reason why there’s been so much innovation over the last several years, the reason why we can talk about six and seven approvals of drugs within half a decade.

And many of the drugs that we have at our centers will likely become standard of care in the near future. So, it gives us access to important drugs a little bit in advance of when they might be available for patients through FDA approval. So, it a lot of hope; it’s a lot of innovation. And the major message I would say to patients is don’t think of a clinical trial is for when all options have run out, but oftentimes there are great trial options that are aiming to improve the current standard of care in the frontline and also the relapsed/refractory settings.

Katherine:                  

What’s involved in patient participation in clinical trials?

Dr. Mato:                   

Well, the process is called informed consent, and so, if you’re interested in a clinical trial, you have a conversation with your oncologist to review the study, the schedule, the screening procedures. If you’re interested, you sign an informed consent and then begin a process of doing some testing, oftentimes scan, blood work, EKGs, bone marrow biopsy, to try to identify whether or not you’re a good candidate for the study.

Clinical trials are often more rigid than standard of care meaning you have to follow a strict schedule. You have to report everything, side effects, or successes related to the clinical trial. And oftentimes, a clinical trial is performed at the particular center that you signed the consent. And so, if you came to our center at MSK, odds are you would have to have treatment at our center in order to participate in that trial.

Once you’re enrolled on the trial, you’re on a strict schedule. You work with the physician and a research team, often a nurse directly who specializes in clinical trials to help ensure that you’re monitored appropriately and that the trial is successful for the patient.

Katherine:                  

Now that we understand how trials work, let’s get into developing research. Let’s get into developing research and what it can mean for patients. What new approaches are showing promise?

Dr. Mato:                   

Wow, that’s a loaded question because there’s so many possible answers. There are new versions of the current standards of care, different classes like BTK inhibitors or PI3K inhibitors which have the potential to be very active but better tolerated

So, that’s one big group of new agents in development. There are several agents in development that appear to be effective in the setting of resistance to the current standards of care. There are classes of immunotherapies that allow us in different ways to use the immune system of the patient to fight cancer directly, so not necessarily targeting the cancer cell but targeting the immune system to make it do its job to filter out the cancer.

There are new antibodies in development. And that’s just a little slice of what’s in development for CLL and new combinations of course of the current standards of care which when put together could be even more effective. So, –

Katherine:                  

What about – oh, go –

Dr. Mato:                   

Sorry. I was just gonna add that so many different possibilities available that not every center can participate in all of these types of research, but it’s amazing for patients to know how many different new options are in development that maybe even better than the current approaches.

Katherine:                  

Right. What kind of side effects might be involved with the emerging treatments? What might people expect?

Dr. Mato:                   

That’s a hard question to answer because the purpose of the clinical research is to help define the side effects associated with these newer drugs. And so, while we have a hint from early data or from Phase One data what a side effect profile might look like for a new drug, part of the consenting process is to help gather information not only about a drug’s activity but also about its side effect profile.

So, when we consent a patient, there is a little bit of an unknown about side effects, and we have sometimes very limited information that we can share about the activity. So, it’s not easy to just group these together and say these are the newest side effects to worry about. That’s really the purpose of the studies that I’m mentioning and the general idea of clinical research.

Katherine:                  

And that makes sense. How is research into the genetics of CLL providing a better understanding of how a patient’s individual disease may behave?

Dr. Mato:                   

Well, just a few years ago, the basic genetic studies for CLL included just a few chromosomal markers that we could easily or sometimes not so easily test. At our center for example, and it’s not unique, we’ll be able to look at the over 400 different mutations associated with hematologic malignancies. The more information we get, the more we realize that although under the microscope a CLL cell may look like another CLL cell, biologically, they’re very different.

They’re driven by different genetic mutations, and knowledge of those pathways that are important for an individual CLL will oftentimes, will hopefully in the future guide how therapy is selected for patients.

Katherine:                  

It sounds like there is a lot of very interesting research going on as more is being learned from the molecular – as more is being learned from molecular or genetic testing in CLL. And that leads us to our next topic. Why is it important to stay informed as new treatments become available?

Dr. Mato:                   

Well, the field is moving at such a rapid, and I would say up until very recently, every six to eight months we’ve had a new drug approved for CLL for a long period of time. So, it’s important to stay informed because in a good way, the standard of care and the pace of research is very quick and that maybe not all oncologists are as up-to-date about what’s going on in the field.

And so, through patient organizations and through webinars like this and through working closely with patient and professional societies and also with CLL experts, it’s very important to stay up-to-date not only about new therapies but about prognostic markers and about emerging clinical trials which be a benefit to an individual patient.

Katherine:                  

What are some of the credible sources that can help patients stay informed and up-to-date?

Dr. Mato:                   

I think there are several societies which I just kind of at the top of my mind I can think of which there’s credible information.

I hate to create and list and say it’s exhaustive because I’m sure I’m forgetting somebody, but Lymphoma Research Foundation has great information, Leukemia & Lymphoma Society, the CLL Society, Patient Power, there’re just many organizations that are patient-focused that have educational materials, support groups, webinars, access to CLL experts, and interviews available that are very useful, and there are several that I’m omitting.

Katherine:                  

That’s fine. We’ll go into that with our slides probably.

Dr. Mato:                   

Not intentionally by the way, just because I can’t remember every single organization, but there’s a lot of resources available for patients. I guess the one thing I would advise against is getting too mired into chat rooms or conversations that are a little bit unfiltered because it’s very hard to translate one patient’s experience to another. And I think sometimes that a chat room without a moderator or a patient support group that doesn’t have a filter in it somehow to try to understand where the questions are or concerns are coming from can sometimes lead to a lot of anxiety for patients.

Katherine:                  

Yeah. That’s really good advice. If a patient’s physician doesn’t seem really knowledgeable about research and the latest treatments, do you recommend a patient consider a second opinion or even ultimately consult a specialist?

Dr. Mato:                   

Yeah, I think even for my own patients as a CLL expert, I never discourage a second opinion. There’s always something that can be learned for the patient and the physician from that experience. Anybody who has a physician who is very resistant to allow them to get a second opinion, I think that that’s probably a tell-tale sign that they’re not the best fit for the patient.

So, I don’t like to say that every patient has to have a CLL expert. But if a patient has questions that aren’t being answered, they certainly should seek advice. There are many community oncologists who are wonderful doctors. They’re very caring. They’re very good at taking care of patients. And a CLL expert is not always needed. But if you do have a community oncologist, and they come to see me for example, we work very happily with the local doctor to partner together.

And I view it as the need – I view it as a partnership where we can work with the doctor, and it doesn’t have to be a choice. And so, if a patient ever feels they’re put in a situation where they have to choose one doctor over another, there’s probably too many egos involved, and they should think long and hard about finding new help.

Katherine:                  

Yeah. Let’s take one last audience question, Dr. Mato. I am IGHV mutated, young, and healthy, and I wanna participate in a clinical trial. How do I find one that’s right for me?

Dr. Mato:                   

That’s a great question. So, IGHV mutational status is a prognostic factor that largely defines prognosis in the setting in the need for chemotherapy. So, IGHV mutated patients typically do better when they receive chemotherapy versus IGHV unmutated patients. In the modern area where we’re talking about BTK inhibitors and some of the other drugs, for example, the outcomes are quite similar whether you’re mutated or unmutated.

I think the search for a clinical trial probably should not be based on the IGHV mutational status, but the fact that you’re a young patient and you’re looking for a clinical trial that may have a little bit of a different focus intent in terms of depth of remission or ability to stop therapy rather than just a specific focus on the IGHV status driving that decision.

What I would advise for a young person is that it’s probably very reasonable to be seen in a major academic center where there are more patients who are younger and therefore clinical trials which may have a focus on a younger patient population. And in the world of CLL where the average age is 70 or 71 at diagnosis, younger maybe 60 or 65 or 55. I’m not necessarily talking about a 25-year-old when I say younger. I don’t know this particular patient’s age.

Katherine:

Right. I’m not sure either. Many of these newer therapies are pills or oral therapies.

How do you ensure that the patient is taking the medicine as prescribed, and with COVID now in our lives on a daily basis, how has this been affected by COVID?

Dr. Mato:                   

So, how do we ensure patients are taking their medicines? That’s a good question. It’s not an exact science. So, part of it is we rely on the patient to tell us that they’re taking the medications. We can guestimate that they’re taking patients based on their requests for refills. So, if we give a 30-day supply and they request a refill in 60 days, they’re probably not taking it appropriately.

Sometimes, patient diaries are used. We have a whole team who sees our patients including a nurse, a nurse practitioner, a clinical pharmacist who can help gauge whether or not a patient is adherent to a schedule. And then if you’re on a clinical trial, then you often have to keep a pill diary, and a research nurse will do drug accountability assessments with patients when they’re seen in the office, so lots of different ways to answer the same question.

Has COVID affected things? A little bit during the height of the pandemic in the New York area. There might’ve been some slight delays to starting CLL-based therapy because of concerns for risk of infection, sort of risk/benefit. Currently, based on my region at least, we are treating patients. We’re not withholding therapy or delaying therapy based on the theoretical risk for COVID infection, but we’re making decisions that we think are in the best interest of the patients based on their CLL and their need for therapy.

That may be different in other areas of the country right now. We always have to weigh the risk/benefit of infection and other circumstances versus the need for CLL-directed therapy.

Katherine:                  

Before we close, Dr. Mato, how do you feel about the future of CLL treatment? Are you hopeful?

Dr. Mato:                   

I’m extremely hopeful and optimistic. I think for me, I trained as an oncologist with the hope of being able to take care of patients with CLL.

I always liked taking care of patients with CLL. It’s a passion to provide great care to help provide development or to participate in research that changes the standard of care, and every day I’m amazed with some of the molecules we work with and how much or how they’ll be able to help patients in the future and of course, taking care of patients and seeing this is in the clinic is really the best and most gratifying experience for anybody who’s involved in CLL research to see our patients who are very sick become well and go back to work or resume their normal life is really the most rewarding part of being part of the specialty.

Katherine:                  

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

Dr. Mato:

Thank you for having me, and I’m really, really thankful for participating in this program.

Katherine:

And thank you to all of our partners. 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 today, and please make sure to fill out the survey that you receive after the program. It helps us as we develop more webinars like this one.

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What Should You Know About the Future of CLL Treatment?

What Should You Know About the Future of CLL Treatment? from Patient Empowerment Network on Vimeo.

As chronic lymphocytic leukemia (CLL) research continues to expand, more treatment options for patients with CLL are emerging. Dr. Susan O’Brien, a hematology-oncology specialist, discusses recent CLL treatment developments.

Dr. Susan O’Brien is the Associate Director for Clinical Science, Chao Family Comprehensive Cancer Center.

See More From The Pro-Active CLL Patient Toolkit


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Should You Discuss a CLL Clinical Trial with Your Doctor?

 How to Be A Partner in Your CLL Care  Key CLL Treatment Decision-Making Factors

Transcript:

Katherine:

All right. How do you feel – how do you feel about the future of CLL treatment? Are you hopeful?

Dr. Susan O’Brien:

Absolutely. I think we’ve had something like six drugs approved in the last seven years, which is mindboggling. I think in the 30 years before that, we didn’t even have six drugs approved. That’s how rapidly – it’s mindboggling, really. That’s how rapidly the field is moving forward. And not just CLL, but other cancer fields also are moving at a very dizzying pace.

Which is great because that – anything that gives us more options is wonderful. So, I am very, very optimistic about CLL going forward. And I’m also very hopeful that some of these combination regimens might actually be – small molecules might actually be curative in the long run. But I will say it’s way too early to know that.

Katherine:                  

Are there emerging treatments that patients should know about?

Dr. Susan O’Brien:     

So, one of the categories we haven’t talked about, where there actually are two FDA approved drugs, are PI3K inhibitors – that’s another oral small molecule. They’re not approved for frontline therapy. So, that’s kind of why we weren’t talking about them so much today where we’re talking about making a choice for the first therapy. But they are approved for patients where the disease reoccurs.

And there’s two of those as we mentioned. We have antibodies, which we really haven’t talked about very much, and then there’s new classes of drugs that are being explored in clinical trials. So, for example, there are interesting drugs which are antibodies that bind to the patient’s own T-cells and they also mind the CLL cells and they redirect the T-cells towards the CLL cells.   

Kind of like CAR-T but inside the body without having to take out the T-cells. So, those are really interesting class of drugs. None have been yet approved in CLL or lymphoma, but I think those are on the horizon and looking very promising.