Tips for Managing Your Oral CLL Treatment Schedule

Tips for Managing Your Oral CLL Treatment Schedule from Patient Empowerment Network on Vimeo.

Patients taking an oral CLL therapy have a responsibility in managing their own care. Dr. Jean Koff, a CLL expert from Winship Cancer Institute of Emory University, discusses the importance of staying on schedule with medications and shares advice for being consistent.

Dr. Jean Koff is an Assistant Professor in the Department of Hematology and Oncology at Winship Cancer Institute of Emory University. Learn more about Dr. Koff, here.

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Transcript:

Katherine Banwell:

With oral medications available to treat CLL, patients now have the role of self-administering with their treatment program. How does this work exactly?  

Dr. Jean Koff:

So, just as you would receive a prescription from one of your doctors to manage your high blood pressure with a bottle of pills, you would also receive a special prescription from the doctor who is managing your CLL, a prescription for one of these oral agents. Either the BTK inhibitors or a venetoclax. And you would be – you would have the instructions on the pill bottle, just as you would you know another prescription, and you would take the medication by mouth, every day, as instructed.  

Katherine Banwell:

Okay. What happens if a patient forgets to take their medication? Does it impact efficacy? 

Dr. Jean Koff:

So, forgetting a dose for one day, or having to skip a dose for another reason, or even a few days, shouldn’t have a major impact on controlling the CLL. And that’s true for two reasons. One, you’re going to start taking your medication again, you know fairly soon after you miss that dose. The next day or – or in a few days. But also, the – what we call the half-lives of these drugs are relatively long, and so you have some activity of the drug in your system in its ability to control the CLL, even though you haven’t taken the dose that you missed that day. In fact, sometimes we have to hold CLL medications.  

Maybe you’re getting a procedure, some sort of surgical procedure, and you might be at an increased risk of bleeding just in the day or two before and after that surgical procedure, so we would actually recommend that you hold a BTK inhibitor, if that was what you were receiving for your CLL, and then resume it once your risk of bleed had gone down a few days after the surgery.   

We do recommend that if you are going to miss a dose of your medication that you let your clinical team know, just so they can instruct you on how to resume your dose if you haven’t already gotten instructions from them about that. 

Katherine Banwell:

Okay. That’s really helpful information. What strategies are there to keep on schedule and remember to take the medication on time and regularly?  

Dr. Jean Koff:

So, I think these strategies are good whether you have CLL or some other type of disorder that you’re taking medication for. My patients often use labeled pill boxes with days of the week and a.m. and p.m., so that you know whether you took your pill that day and what time of day you took it. And so, setting that out for the week can be very helpful in organizing and making sure that you can check back and remind yourself whether or not you took your pill. 

Katherine Banwell:

How are patients monitored during treatment?  

Dr. Jean Koff:

So, your doctor is going to monitor you more closely when you first start a medication. So, I typically monitor my patients within one or two weeks of them starting an oral drug. One to make sure that they’re feeling okay on it, that they’re not having any side effects when they first start, but also to check lab values and make sure that the – the oral medication isn’t causing any problems with their blood counts or with other labs. Then, once we’ve established that they’re doing well on the medication, maybe they’ve come in every couple weeks for a month or six weeks, we start to space out those visits.  

I usually see my patients who are on active therapy about every three to six months to check and see whether they’re feeling okay, whether they’re having any side effects from the medicines, like I said to check their labs, make sure the medications aren’t causing any lab abnormalities. And also in the longer term, to make sure that their CLL is under good control on – on the medications. Because that’s one of our main goals is to keep the CLL under good control.  

Can a CLL Patient’s Response to the COVID Vaccine Be Boosted?

Can a CLL Patient’s Response to the COVID Vaccine Be Boosted? from Patient Empowerment Network on Vimeo.

Is there a way to boost COVID vaccine response in patients with CLL? Dr. Jean Koff explains ongoing progress being made to protect CLL patients from COVID.

Dr. Jean Koff is an Assistant Professor in the Department of Hematology and Oncology at Winship Cancer Institute of Emory University. Learn more about Dr. Koff, here.

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Transcript:

Katherine Banwell:

We received another patient question prior to the program. Has there been any progress in helping CLL patients get a better reaction from COVID vaccines? 

Dr. Jean Koff:

That is a great question, and that is one that is near and dear to my heart and my colleagues at – at Emory. You raise a really good point, which is that CLL patients have altered immune systems just by virtue of their CLL. The CLL cells exert their influence on other immune cells and can cause your immune system not to respond to infections or immunizations the way it normally would. That’s without any medication in the mix. Now, when we look at patients who are on medications like the ones we’ve been talking about, the BTK inhibitors, venetoclax (Venclexta), but especially the monoclonal antibodies that react against CD20, we see that those patients really do not have an optimal response to vaccines, especially the COVID vaccine. 

Meaning, that patients who receive the COVID vaccine while they’re on that therapy, or even within 12 months of receiving a monoclonal antibody, often don’t mount the same strong immune response as somebody who’s not on those therapies. So, luckily, we – we don’t have to just depend on the vaccines. I still recommend that my patients get vaccinated, because it is safe and it might impart a little bit of efficacy, and it’s certainly more effective than not getting the vaccine. But we also have other approaches to increasing your protection against COVID, including the – the injection called tixagevimab co-packaged with cilgavimab (Evusheld), which can help protect patients specifically whose immune systems are not completely normal and are not expected to mount a strong response to COVID vaccines.  

So, that is definitely a discussion to have with your doctor about how your medications impact your protection from COVID, from vaccines, and whether there are other medications that might be used to help increase your protection.   

Katherine Banwell:

That’s great advice.  

What is YOUR Role in Choosing a CLL Treatment Approach?

What Is YOUR Role in Choosing a CLL Treatment Approach? from Patient Empowerment Network on Vimeo.

Dr. Jean Koff shares her perspective on the role of patient when deciding on a CLL treatment approach and reviews key factors that should be considered.

Dr. Jean Koff is an Assistant Professor in the Department of Hematology and Oncology at Winship Cancer Institute of Emory University. Learn more about Dr. Koff, here.

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Transcript:

Katherine Banwell:

What is the patient’s role in deciding on a treatment plan? 

Dr. Jean Koff:

So, it’s very important that the patient be involved in deciding on a treatment plan. Especially in first-line. Because we have these two excellent classes of agents, the BTK inhibitors and the venetoclax- containing regimens. Both of them have been shown to have very good what we call efficacy CLL, meaning that they’re able to control the disease, patient’s symptoms largely at bay for long periods of time. You know, we’re talking an average of years that – that patients are on these therapies. And they each, like I said have different side effect profiles.  

And they’re given in slightly different ways. And so, right now we don’t have data from our clinical trials comparing a BTK inhibitor regimen to a venetoclax-containing regimen in CLL patients to tell us one is better than the other. And so, for that reason, a lot of the decision-making about which therapy is going to be better for you, or which therapy you would prefer, lies with the CLL patient rather than with the doctor. And the things that I ask my patients to consider, there are a couple different things. One is the side effect profile. So, patients may be more or less comfortable with certain  

side effects of one drug compared to another. Or there may be something in the patient’s medical history that puts them more at risk for a certain side effect than another. 

The other major player in this decision-making process is how these drugs are given. So, with ibrutinib (Imbruvica), the ibrutinib is given as a pill that you take once a day, and you take it indefinitely. Meaning you take that pill once a day for as long as it’s doing what it’s supposed to do, which is keeping your CLL under control, and as long as the patient is tolerating it well, meaning you’re not having a lot of uncomfortable side effects from the ibrutinib. So, I have patients who have been on ibrutinib for years and years and years and years.  

The venetoclax-containing regimen for patients who are getting their first-line treatment in CLL is different. It is designed as a – what we call time-limited therapy. And so, this regimen is given in – over about 12 months, 12 or 13 months, and then stopped, as long as the patient has had a good response. The other thing to consider with the venetoclax r egimen, it’s not just the pill. You do take a pill every day, but you also get a – an infusion for about six months of the monoclonal antibody. Meaning that you’ll have to come into the infusion center and get an infu – an IV infusion of this drug called obinutuzumab. The last consideration with the venetoclax regimen that differs in how it’s administered, is the venetoclax often works so well that it can break down the CLL cells a little bit too quickly. And so, for patients who have a very, very high white count, or large lymph nodes due to their CLL, there is a risk of something we call tumor lysis syndrome, which refers to the process where the tumor cells break down very, very quickly, and they produce molecules that are released into the bloodstream that can be dangerous if they get too high or too low. And so, sometimes, in some patients we have to monitor for the tumor lysis syndrome by checking labs fairly frequently after we start the venetoclax. And for some patients that means they have to stay overnight for a night or two in the hospital for lab monitoring.  

So, for some of my patients that I talk to about venetoclax, they say I want to stay out of the hospital, I just want to take a pill, I’m fine taking a pill, I’ll go with the BTK inhibitors. For other patients, they say I don’t want to be on a pill every single day, I will go through this year of therapy, I’m comfortable with that, and I’m happy that I’ll be able to take a break from therapy after one year. So, that ends up being a large factor in many of the conversations I have with my patients about which therapeutic approach we’re going to use in front-line therapy.  

What Do You Need to Know About CLL Treatment Side Effects?

What Do You Need to Know About CLL Treatment Side Effects? from Patient Empowerment Network on Vimeo.

CLL Expert Dr. Jean Koff discusses common side effects of CLL treatment and explains how they can be managed.

Dr. Jean Koff is an Assistant Professor in the Department of Hematology and Oncology at Winship Cancer Institute of Emory University. Learn more about Dr. Koff, here.

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Transcript:

Katherine Banwell:

What are the common side effects of treatments, and how are they managed? 

Dr. Jean Koff:

So, each of the different classes of agents has a different profile of side effects. The BTK inhibitors, the first class that I mentioned with ibrutinib (Imbruvica) and acalabrutinib (Calquence), are usually very well tolerated. The most common side effects that we tend to see are things that the patients can feel or see, but also things that we can see on the labs when we’re monitoring patients. So, sometimes you can see a lower platelet counts or lower blood cell counts with ibrutinib. That’s something that you may not notice, but your doctor’s going to notice on the – the blood counts when you come to the office. Sometimes ibrutinib can cause a rash or GI upset, this is usually easily managed with supportive care from your physician.  

And then some more – some more common effects of the BTK inhibitors include joint pain and headache. And again, many physicians, because we’ve been using BTK inhibitors for a long time, have a good regimen for treating these side effects. More uncommon side effects of BTK inhibitors, particularly ibrutinib that we look out for would be abnormal heart rhythms and some tendency for bleeding. But these are relatively uncommon and with newer BTK inhibitors, we’re seeing lower rates of these side effects.  

Dr. Jean Koff:

So, in terms of venetoclax side effects we have a little bit of a different profile. This agent is much more likely to cause lower cell counts, especially in a white blood cell count known as neutrophil count, and so your doctor will be monitoring you for that. In terms of patient side effects that you can feel, it can cause a rash, it can cause some GI upset. These are usually relatively easily managed but we want you as the patient if you’re on venetoclax to talk to your doctor about these side effects so that they can help you feel better and help you manage those. In terms of the anti-CV20 monoclonal antibodies, which we use a couple in CLL more frequently, they have very similar side effect profiles.  

So, one is rituximab, and one is obinutuzumab. Obinutuzumab is usually used in combination with venetoclax in front-line CLL.  

Like I mentioned before, this is an infusion and most of the side effects that we think about and most commonly see in these anti-CV20s are side effects that patients have during the infusion. And these are referred to as infusion reaction. And these are relatively common, around 30 percent in these anti-CV20 monoclonal antibodies. So, what is an infusion center react – er sorry, what does an infusion reaction look like? This looks sort of like an allergic reaction. 

Katherine Banwell:

Hm. 

Dr. Jean Koff:

So, your nurses in the infusion center are going to be monitoring you very carefully once you start the infusion, and they’re going to start it at a low dose, very slowly. But the side effects they’re monitoring for, they’re looking for changes in your heart rate or blood pressure. You may start to feel hot or cold or sweaty, you may have chills. Sometimes patients can have swelling in their throat or their tongue. And what will happen is because these are fairly common, is we’re still able to give the anti-CV20, but what we do is the nurse will stop the infusion, they may give you some medications that calm down that infusion reaction. So, medications like antihistamines –  

Katherine Banwell:

Mm-hmm.  

Dr. Jean Koff:

Or steroids that help tamp down that immune response, and then they start the anti-CV20 infusion at a lower rate. The vast majority of patients will be able to receive an anti-CV20 antibody even if they have an infusion reaction. They may just need a little bit more of those immune tamping-down medications like antihistamines and steroids. And then the last thing to consider, which I think we’ve mentioned, especially in the venetoclax-containing regimens, is the tumor lysis syndrome. And so, that is a side effect like we mentioned is kind of like the venetoclax working really, really, really well, of the tumor breaking down too quickly.  

And so, patients who have tumor lysis, if they’re at high-risk, hopefully they’re already being monitored very closely with frequent lab draws, and they may receive medications that – that diminish the risk of adverse events happening because your electrolytes are out balance, for instance, your potassium is too high, or your calcium is too low. Because your doctors are monitoring you closely, they can give you medications that can help balance  out those – those electrolytes and help protect the kidneys. The tumor lysis is typically not a risk after the initial doses of venetoclax.  

So, the first couple weeks is when we typically monitor that, and then once the CLL has been broken down, or as I like to say, once it’s been cooled off a little bit, then you no longer have this risk of tumor lysis and it – it doesn’t require further monitoring. 

Katherine Banwell:

That’s great information, thank you.  

What Are the Current CLL Treatment Options?

What Are the Current CLL Treatment Options? from Patient Empowerment Network on Vimeo.

When is it time to treat CLL, and what are the current options? Dr. Jean Koff, from the Winship Cancer Institute of Emory University, reviews available CLL treatment approaches and discusses patient-specific factors that she considers when choosing therapy.

Dr. Jean Koff is an Assistant Professor in the Department of Hematology and Oncology at Winship Cancer Institute of Emory University. Learn more about Dr. Koff, here.

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Transcript:

Katherine Banwell:

Many patients are overwhelmed by the different types and classes of treatment. When is it time to treat CLL, and what are the options? 

Dr. Jean Koff:

So, I boil down the criteria to when you need to treat your CLL to two main categories. One category is that the disease is progressing quickly, and the other category is the disease is causing problems of some kind, or getting ready to cause problems of some kind. Those are some of the broad categories that we think about when it’s time to start treatment for CLL. Now, this – the groups that research CLL have put out various criteria that help guide physicians about when it’s time to start treatment, and some of those more specific criteria include items like symptoms. So, symptoms are a very important part of that decision-making process.   

And the same symptoms that we mentioned, the B symptoms, fevers, chills, night sweats, weight loss that’s unintentional, or lymph nodes that you can feel, those would potentially be reasons that your doctor would want to start you on CLL therapy. But the CLL can cause issues even in a patient who’s not necessarily having symptoms. So, one of the most common ways that CLL can cause issues is the CLL cells can cause your other blood cells, the normal blood cells, to be low in number. There are several ways the CLL cells can do this. One of the most common ways is that the CLL cells, which are often circulating through your bloodstream, can also collect or overrun your bone marrow.  

And if you think about it, the bone marrow is the factory that makes all of your blood cells. So, when there are too many CLL cells in the bone marrow, they can crowd out the normal blood cells, like red blood cells or platelets. So, when red blood cells or platelets get low beneath certain thresholds, that’s a reason to start CLL therapy. 

Katherine Banwell:

Mm-hmm.   

Dr. Jean Koff:

So, there are a couple other criteria that we think about. CLL cells can collect in other areas, including the spleen. So – and if you remember, the spleen is a lymphoid organ that sits on the left side of your body that is right below the stomach. And so, if CLL cells collect in the spleen, they can cause it to be too big, it can press on the stomach, it can make it so you feel full, even if you haven’t eaten a full meal, that’s something we call early satiety. It can be uncomfortable, causing some abdominal pain. And if the spleen gets really, really big, it can cause it to not be able to do its normal job, which is to filter out the normal blood cells like it does every day. And so, that would be a reason to start therapy as well. And then the last – the last category I would think about is in CLL we have lots of – of CLL cells that are circulating in the blood that we can check with a routine blood count. And the absolute number of CLL cells is not as important as how fast that number is growing. So, your physician will track how fast that number of CLL cells is doubling.  

And if you meet criteria for what we call rapid doubling time, which is usually thought of as less than 12 months but certainly less than six months. So, if your count goes from 30,000 to 60,000 in under six months, then it may be time for you to start thinking about therapy. 

Katherine Banwell:

Right. So, Dr. Koff, would you briefly review the treatment classes? 

Dr. Jean Koff:

So, for first-line treatment, we have two main treatment classes that we think about at this time. The first is – is called BTK inhibitors, which is Bruton tyrosine kinase inhibitors. And these are oral medications, so medications that you take by mouth, and the most well-studied of these is called ibrutinib (Imbruvica), we typically prescribe ibrutinib by itself. There are other BTK inhibitors we are also now using in this space, one of them is called acalabrutinib  (Calquence), and that is often given with an IV monoclonal antibody called obinutuzumab (Gazyva).   

The other main class of drugs that we consider for first-line treatment of CLL is the BCL-2 inhibitors. Right now there’s only one BCL-2 inhibitor that’s approved for CLL and front-line and it’s called venetoclax (Venclexta). Usually, this drug is also given in the front-line with an anti-CD20 monoclonal antibody. So, the venetoclax itself is a pill you take. And the monoclonal antibody is an – either an IV or a subcutaneous injection.  

Katherine Banwell:

Where do clinical trials fit into CLL treatment? 

Dr. Jean Koff:

So, clinical trials are part of the reason, a big part of the reason that we’ve been able to make so much progress in how we treat CLL over the past few years. Clinical trials are how we figure out what treatments work for CLL, how patients feel on them, what sort of adverse events or side effects they have on individual treatments, and which treatments do better for keeping CLL symptoms under control, keeping the disease under control, and allowing patients to live longer and have a higher quality of life with their disease.   

Katherine Banwell:

Are there any other options available for CLL patients?  

Dr. Jean Koff:

So, there are other options. A clinical trial, if that is available to you as a patient is nearly always a good thing to consider if you have CLL. Because the vast majority of patients will not be cured by CL – by their treatment for CLL. Meaning that the – even though the treatments we have usually work for a very long time in most patients, ultimately the CLL will at some point, perhaps years down the road, progress and need another therapy. For that reason, we know we can do better. And we are hoping that the next  clinical trial is going to lead to the discovery of a new agent or a new combination – new  combinations of agents that will allow patients to live longer with a better quality of life with CLL.  

Katherine Banwell:

Mm-hmm. 

Dr. Jean Koff:

So, that’s always a good option to consider.  

How Are CLL Symptoms Treated?

How Are CLL Symptoms Treated? from Patient Empowerment Network on Vimeo.

Dr. Jean Koff reviews common CLL symptoms and explains why patients should discuss any issues they experience with their healthcare teams.

Dr. Jean Koff is an Assistant Professor in the Department of Hematology and Oncology at Winship Cancer Institute of Emory University. Learn more about Dr. Koff, here.

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Transcript:

Katherine Banwell:

One part of thriving with CLL is managing the symptoms of the disease. What are the common symptoms of CLL? 

Dr. Jean Koff:

So, one thing that I see with nearly all of my CLL patients, regardless of where they are in the CLL journey, and regardless of whether they need active medications to manage their CLL, is some degree of fatigue. And this can range from just mild fatigue that patients notice that they need a little bit of a breather in the middle of the day, to needing more sleep at night, to not being able to exercise as much as they’re used to. And that is by far one of the most common symptoms we see. Again, whether or not their disease needs medication to manage it.  

The classic symptoms of CLL that often let us know that it’s time to start medical management are not just this fatigue. But the classic symptoms are  B symptoms. And we describe those as fevers, night sweats, and unintentional weight loss. Those are very common. And then some patients with CLL will also have what we call palpable lymphadenopathy, which is our term for lymph nodes that are enlarged that you can feel. And the most common places to feel these on the body are on the neck, under the arms, and in the groin.  

Katherine Banwell:

Okay. How are symptoms treated? 

Dr. Jean Koff:

So, if your symptoms progress to the point that your doctor thinks you need medication – they’re becoming disruptive to your life, or they are getting worse and worse over time, then there are a variety of medications that we can use in CLL. And this is actually a very exciting field. Right now, the state of the field is that most patients who are starting on their first treatment for CLL will use some sort of oral medication, and that may be accompanied by an IV – what we call monoclonal antibody, or it may not. But one thing that has really changed even since I very first started practicing, is that we no longer commonly use what I would call conventional chemotherapy to treat CLL – even though this was the standard of care just a few years ago. 

Katherine Banwell:

Wow. So, a lot has changed. 

Dr. Jean Koff:

Yes, definitely. 

Thriving With CLL: Your Role in Managing Your Care

Thriving with CLL: Your Role in Managing Your Care from Patient Empowerment Network on Vimeo.

 How can patients thrive with chronic lymphocytic leukemia (CLL)? Dr. Jean Koff discusses CLL treatments approaches, strategies for managing disease symptoms and treatment side effects, and shares advice on how patients can be proactive in their care.

Dr. Jean Koff is an Assistant Professor in the Department of Hematology and Oncology at Winship Cancer Institute of Emory University. Learn more about Dr. Koff, here.

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Transcript:

Katherine Banwell:  

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss what it means to thrive with CLL. And how you can play an active role in your care. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access information to follow along during the webinar. At the end of this webinar, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today, in order to help us plan future webinars.  

And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please speak to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Jean Koff. Dr. Koff, welcome! Would you please introduce yourself? 

Dr. Jean Koff:

Hi, I’m Jean Koff. I’m a lymphoma and CLL specialist from Emory University and it’s a pleasure to be with you here today. 

Katherine Banwell:

Thank you for taking the time to join us. We start all of our webinar in our CLL Thrive series with the same question. In your experience, what does it mean to thrive with CLL? 

Dr. Jean Koff:

So, I think thriving with CLL means that a patient is informed about their disease, they are comfortable with the physician who’s helping them navigate their disease and their management plan. And their management plan, whatever that might be, is really allowing them to focus on their life outside of CLL. So, keeping their symptoms to the absolute minimum, their physician keeping them informed about their disease progress, or lack thereof, in terms of keeping the disease at bay so they can focus on all of those things that bring them enjoyment outside of the CLL world. 

Katherine Banwell:

That’s great. Thank you for your perspective. One part of thriving  with CLL is managing the symptoms of the disease. What are the common symptoms of CLL? 

Dr. Jean Koff:

So, one thing that I see with nearly all of my CLL patients, regardless of where they are in the CLL journey, and regardless of whether they need active medications to manage their CLL, is some degree of fatigue. And this can range from just mild fatigue that patients notice that they need a little bit of a breather in the middle of the day, to needing more sleep at night, to not being able to exercise as much as they’re used to. And that is by far one of the most common symptoms we see. Again, whether or not their disease needs medication to manage it. The classic symptoms of CLL that often let us know that it’s time to start medical management, are not just this fatigue. But the classic symptoms are B symptoms. And we describe those as fevers, night sweats, and unintentional weight loss. Those are very common. And then some patients with CLL will also have what we call palpable lymphadenopathy, which is our term for lymph nodes that are enlarged that you can feel. And the most common places to feel these on the body are on the neck, under the arms, and in the groin.  

Katherine Banwell:

Okay. How are symptoms treated? 

Dr. Jean Koff:

So, if your symptoms progress to the point that your doctor thinks you need medication – they’re becoming disruptive to your life, or they are getting worse and worse over time, then there are a variety of medications that we can use in CLL. And this is actually a very exciting field. Right now, the state of the field is that most patients who are starting on their first treatment for CLL will use some sort of oral medication, and that may be accompanied by an IV – what we call monoclonal antibody, or it may not. But one thing that has really changed even since I very first started practicing, is that we no longer commonly use what I would call conventional chemotherapy to treat CLL. Even though this was the standard of care just a few years ago. 

Katherine Banwell:

Wow. So, a lot has changed. 

Dr. Jean Koff:

Yes, definitely. 

Katherine Banwell:

Why is it so important for patients with CLL to speak up and communicate with their healthcare team about some of their symptoms? 

Dr. Jean Koff:

Well, for starters we want you to feel better. That’s our number one job as – as physicians, is we want to get you to feeling to – to where you are feeling like your best self. CLL or not. So, we want to make you feel better. But in CLL your symptoms are actually one of the criteria we consider when we’re thinking about whether or not we need to start a new therapy, or if you’re somebody who’s already on therapy, whether we need to change your therapy. So, it’s actually very important and your CLL doctor should be checking in with you regularly to see if you have new or worsening symptoms that might be due to your CLL.  

Katherine Banwell:

Mm-hmm. It sounds like treatment of the disease is key to controlling your symptoms. So, let’s talk about treatment. Many patients are overwhelmed by the different types and classes of treatment. When is it time to treat CLL, and what are the options?  

Dr. Jean Koff:

So, I boil down the criteria to when you need to treat your CLL to two main categories. One category is that the disease is progressing quickly, and the other category is the disease is causing problems of some kind, or getting ready to cause problems of some kind. Those are some of the broad categories that we think about when it’s time to start treatment for CLL. Now, this – the groups that research CLL have put out various criteria that help guide physicians about when it’s time to start treatment and some of those more specific criteria include items like symptoms. So, symptoms are a very important part of that decision-making process.  

And the same symptoms that we mentioned, the B symptoms, fevers, chills, night sweats, weight loss that’s unintentional, or lymph nodes that you can feel, those would potentially be reasons that your doctor would want to start you on CLL therapy. But the CLL can cause issues even in a patient who’s not necessarily having symptoms. So, one of the most common ways that CLL can cause issues is the CLL cells can cause your other blood cells, the normal blood cells, to be low in number. There are several ways the CLL cells can do this. One of the most common ways is that the CLL cells which are often circulating through your bloodstream can also collect or overrun your bone marrow.   

And if you think about it, the bone marrow is the factory that makes all of your blood cells. So, when there are too many CLL cells in the bone marrow, they can crowd out the normal blood cells, like red blood cells or platelets. So, when red blood cells or platelets get low beneath certain thresholds, that’s a reason to start CLL therapy. 

Katherine Banwell:

Mm-hmm.   

Dr. Jean Koff:

So, there are a couple other criteria that we think about. CLL cells can collect in other areas, including the spleen. So – and if you remember, the spleen is a lymphoid organ that sits on the left side of your body that is right below the stomach. And so, if CLL cells collect in the spleen, they can cause it to be too big, it can press on the stomach, it can make it so you feel full, even if you haven’t eaten a full meal, that’s something we call early satiety. It can be uncomfortable, causing some abdominal pain. And if the spleen gets really, really big, it can cause it to not be able to do its normal job, which is to filter out the normal blood cells like it does every day. And so, that would be a reason to start therapy as well. And then the last – the last category I would think about is in CLL we have lots of – of CLL cells that are circulating in the blood that we can check with a routine blood count. And the absolute number of CLL cells is not as important as how fast that number is growing. So, your physician will track how fast that number of CLL cells is doubling.  

And if you meet criteria for what we call rapid doubling time, which is usually thought of as less than 12 months but certainly less than six months. So, if your count goes from 30,000 to 60,000 in under six months, then it may be time for you to start thinking about therapy. 

Katherine Banwell:

Right. So, Dr. Koff, would you briefly review the treatment classes? 

Dr. Jean Koff:

So, for first-line treatment, we have two main treatment classes that we think about at this time. The first is – is called BTK inhibitors which is Bruton tyrosine kinase inhibitors. And these are oral medications, so medications that you take by mouth, and the most well-studied of these is called ibrutinib, we typically prescribe ibrutinib by itself. There are other BTK inhibitors we are also now using in this space, one of them is called acalabrutinib and that is often given with an IV monoclonal antibody called Obinutuzumab.   

The other main class of drugs that we consider for first-line treatment of CLL is the BCL-2 Inhibitors. Right now there’s only one BCL-2 Inhibitor that’s approved for CLL and front-line and it’s called venetoclax. Usually, this drug is also given in the front-line with an anti-CD20 monoclonal antibody. So, the venetoclax itself is a pill you take. And the monoclonal antibody is an – either an IV or a subcutaneous injection.  

Katherine Banwell:

Where do clinical trials fit into CLL treatment? 

Dr. Jean Koff:

So, clinical trials are part of the reason, a big part of the reason that we’ve been able to make so much progress in how we treat CLL over the past few years. Clinical trials are how we figure out what treatments work for CLL, how patients feel on them, what sort of adverse events or side effects they have on individual treatments, and which treatments do better for keeping CLL symptoms under control, keeping the disease under control, and allowing patients to live longer and have a higher quality of life with their disease.  

Katherine Banwell:

Are there any other options available for CLL patients? 

Dr. Jean Koff:

So, there are other options. A clinical trial, if that is available to you as a patient is nearly always a good thing to consider if you have CLL. Because the vast majority of patients will not be cured by CL – by their treatment for CLL. Meaning that the – even though the treatments we have usually work for a very long time in most patients, ultimately the CLL will at some point, perhaps years down the road, progress and need another therapy. For that reason, we know we can do better. And we are hoping that the next clinical trial is going to lead to the discovery of a new agent or a new combinations – new combinations of agents that will allow patients to live longer with a better quality of life with CLL.   

Katherine Banwell:

Mm-hmm. 

Dr. Jean Koff:

So, that’s always a good option to consider. 

Katherine Banwell:

Mm-hmm. What are the common side effects of treatments, and how are they managed? 

Dr. Jean Koff:

So, each of the different classes of agents has a different profile of side effects. The BTK inhibitors, the first class that I mentioned with ibrutinib and acalabrutinib, are usually very well tolerated. The most common side effects that we tend to see are things that the patients can feel or see, but also things that we can see on the labs when we’re monitoring patients. So, sometimes you can see a lower platelet counts or lower cell counts with ibrutinib. That’s something that you may not notice, but your doctor’s going to notice on the – the blood counts when you come to the office. Sometimes ibrutinib can cause a rash or GI upset, this is usually easily managed with supportive care from your physician.  

And then some more – some more common effects of the BTK inhibitors include joint pain and headache. And again, many physicians, because we’ve been using BTK inhibitors for a long time, have a good regimen for treating these side effects. More uncommon side effects of BTK inhibitors, particularly ibrutinib that we look out for would be abnormal heart rhythms and some tendency for bleeding. But these are relatively uncommon and with newer BTK inhibitors, we’re seeing lower rates of these side effects.  

So, in terms of venetoclax side effects we have a little bit of a different profile. This agent is much more likely to cause lower cell counts, especially in a white blood cell count known as neutrophil count, and so your doctor will be monitoring you for that. In terms of patient side effects that you can feel, it can cause a rash, it can cause some GI upset. These are usually relatively easily managed but we want you as the patient if you’re on venetoclax to talk to your doctor about these side effects so that they can help you feel better and help you manage those. In terms of the anti-CV20 monoclonal antibodies, which we use a couple in CLL more frequently, they have very similar side effect profiles.   

So, one is rituximab, and one is obinutuzumab. Obinutuzumab is usually used in combination with venetoclax in front-line CLL.  

Like I mentioned before, this is an infusion and most of the side effects that we think about and most commonly see in these anti-CV20s are side effects that patients have during the infusion. And these are referred to as infusion reaction. And these are relatively common, around 30 percent in these anti-CV20 monoclonal antibodies. So, what is an infusion center react – er sorry, what does an infusion reaction look like? This looks sort of like an allergic reaction.  

Katherine Banwell:

Hm.  

Dr. Jean Koff:

So, your nurses in the infusion center are going to be monitoring you very carefully once you start the infusion, and they’re going to start it at a low dose, very slowly. But the side effects they’re monitoring for, they’re looking for changes in your heart rate or blood pressure. You may start to feel hot or cold or sweaty, you may have chills. Sometimes patients can have swelling in their throat or their tongue. And what will happen is because these are fairly common, is we’re still able to give the anti-CV20, but what we do is the nurse will stop the infusion, they may give you some medications that calm down that infusion reaction. So, medications 

 like antihistamines –  

Katherine Banwell:

Mm-hmm. 

Dr. Jean Koff:

Or steroids that help tamp down that immune response, and then they start the anti-CV20 infusion at a lower rate. The vast majority of patients will be able to receive an anti-CV20 antibody even if they have an infusion reaction. They may just need a little bit more of those immune-tamping down medications like antihistamines and steroids. And then the last thing to consider, which I think we’ve mentioned, especially in the venetoclax-containing regimens, is the Tumor lysis syndrome. And so, that is a side effect like we mentioned is kind of like the venetoclax working really, really, really well, of the tumor breaking down too quickly.  

And so, patients who have Tumor lysis, if they’re at high-risk, hopefully they’re already being monitored very closely with frequent lab draws, and they may receive medications that – that diminish the risk of adverse events happening because your electrolytes are out balance, for instance, your potassium is too high, or your calcium is too low. Because your doctors are monitoring you closely, they can give you medications that can help balance out those – those electrolytes and help protect the kidneys. The Tumor lysis is typically not a risk after the initial doses of venetoclax.  

So, the first couple weeks is when we typically monitor that, and then once the CLL has been broken down, or as I like to say, once it’s been cooled off a little bit, then you no longer have this risk of Tumor lysis and it – it doesn’t require further monitoring.  

Katherine Banwell:

That’s great information, thank you. What is the patient’s role in deciding on a treatment plan? 

Dr. Jean Koff:

So, it’s very important that the patient be involved in deciding on a treatment plan. Especially in first-line. Because we have these two excellent classes of agents, the BTK inhibitors and the venetoclax- containing regimens. Both of them have been shown to have very good what we call efficacy in CLL, meaning that they’re able to control the disease, patient’s symptoms largely at bay for long periods of time. You know, we’re talking an average of years that – that patients are on these therapies. And they each, like I said have different side effect profiles.  

And they’re given in slightly different ways. And so, right now we don’t have data from our clinical trials comparing a BTK inhibitor regimen to a venetoclax-containing regimen in CLL patients to tell us one is better than the other. And so, for that reason, a lot of the decision-making about which therapy is going to be better for you, or which therapy you would prefer, lies with the CLL patient rather than with the doctor. And the things that I ask my patients to consider, there are a couple different things. One is the side effect profile. So, patients may be more or less comfortable with certain side effects of one drug compared to another. Or there may be something in the patient’s medical history that puts them more at risk for a certain side effect than another. 

The other major player in this decision-making process is how these drugs are given. So, with ibrutinib, the ibrutinib is given as a pill that you take once a day, and you take it indefinitely. Meaning you take that pill once a day for as long as it’s doing what it’s supposed to do, which is keeping your CLL under control, and as long as the patient is tolerating it well. Meaning you’re not having a lot of uncomfortable side effects from the ibrutinib. So, I have patients who have been on ibrutinib for years and years and years and years.  

The venetoclax-containing regimen for patients who are getting their first-line treatment in CLL is different. It is designed as a – what we call time-limited therapy. And so, this regimen is given in – over about 12 months, 12 or 13 months, and then stopped. As long as the patient has had a good response. The other thing to consider with the venetoclax regimen, it’s not just the pill. You do take a pill every day, but you also get a – an infusion for about six months of the monoclonal antibody. Meaning that you’ll have to come into the infusion center and get an infu – an IV infusion of this drug called Obinutuzumab. The last consideration with the venetoclax regimen that differs in how it’s administered, is the venetoclax often works so well that it can break down the CLL cells a little bit too quickly.  

And so, for patients who have a very, very high white count, or large lymph nodes due to their CLL, there is a risk of something we call Tumor lysis syndrome, which refers to the process where the tumor cells break down very, very quickly, and they produce molecules that are released into the bloodstream that can be dangerous if they get too high or too low. And so, sometimes, in some patients we have to monitor for the Tumor lysis syndrome by checking labs fairly frequently after we start the venetoclax. And for some patients that means they have to stay overnight for a night or two in the hospital for lab monitoring.  

So, for some of my patients that I talk to about venetoclax, they say I want to stay out of the hospital, I just want to take a pill, I’m fine taking a pill, I’ll go with the BTK inhibitors. For other patients, they say I don’t want to be on a pill every single day, I will go through this year of therapy, I’m comfortable with that, and I’m happy that I’ll be able to take a break from therapy after one year. So, that ends up being a large factor in many of the conversations I have with my patients about which therapeutic approach we’re going to use in front-line therapy. 

Katherine Banwell:

Hm. Dr. Koff, we received a patient question prior to the program. If I’ve had FCR for my first treatment, does that prevent me from having – or having to take an oral drug later on? 

Dr. Jean Koff:

Absolutely not. So, the very first clinical trials that we did studying these regiments, especially the BTK inhibitors, were performed in patients who had received conventional chemotherapy like FCR. And what we saw is that patients who had received conventional chemotherapies and had – and needed retreatment of their CLL responded very, very well to agents like ibrutinib. And ibrutinib was able to control their disease, control their CLL, without them needing additional therapy for a long time. And that was actually the original indication for ibrutinib, was patients who had what we call relapsed CLL, often after these conventional therapies.   

Katherine Banwell:

Hm. Let’s turn to medication management. Excuse me. With oral medications available to treat CLL, patients now have the role of self-administering with their treatment program. How does this work exactly? 

Dr. Jean Koff:

So, just as you would receive a prescription from one of your doctors to manage your high blood pressure with a bottle of pills, you would also receive a special prescription from the doctor who is managing your CLL, a prescription for one of these oral agents. Either the BTK inhibitors or a venetoclax. And you would be – you would have the instructions on the pill bottle, just as you would you know another prescription and you would take the medication by mouth, every day, as instructed. 

Katherine Banwell:

Okay. What happens if a patient forgets to take their medication? Does it impact efficacy? 

Dr. Jean Koff:

So, forgetting a dose for one day, or having to skip a dose for another reason, or even a few days, shouldn’t have a major impact on controlling the CLL. And that’s true for two reasons. One, you’re going to start taking your medication again, you know fairly soon after you miss that dose. The next day. Or – or in a few days. But also, the – what we call the half-lives of these drugs are relatively long, and so you have some activity of the drug in your system in its ability to control the CLL, even though you haven’t taken the dose that you missed that day. In fact, sometimes we have to hold CLL medications.   

Maybe you’re getting a procedure, some sort of surgical procedure, and you might be at an increased risk of bleeding just in the day or two before and after that surgical procedure, so we would actually recommend that you hold a BTK inhibitor, if that was what you were receiving for your CLL, and then resume it once your risk of bleed had gone down a few days after the surgery.  

Katherine Banwell:

Hm. 

Dr. Jean Koff:

We do recommend that if you are going to miss a dose of your medication that you let your clinical team know, just so they can instruct you on how to resume your dose if you haven’t already gotten instructions from them about that. 

Katherine Banwell:

Okay. That’s really helpful information. What strategies are there to keep on schedule and remember to take the medication on time and regularly?  

Dr. Jean Koff:

So, I think these strategies are good whether you have CLL or some other type of disorder that you’re taking medication for. My patients often use labeled pill boxes with days of the week and a.m. and p.m., so that you know whether you took your pill that day and what time of day you took it. And so, setting that out for the week can be very helpful in organizing and making sure that you can check back and remind yourself whether or not you took your pill. 

Katherine Banwell:

How are patients monitored during treatment? 

Dr. Jean Koff:

So, your doctor is going to monitor you more closely when you first start a medication. So, I typically monitor my patients within one or two weeks of them starting an oral drug. One to make sure that they’re feeling okay on it, that they’re not having any side effects when they first start, but also to check lab values and make sure that the – the oral medication isn’t causing any problems with their blood counts or with other labs. Then, once we’ve established that they’re doing well on the medication, maybe they’ve come in every couple weeks for a month or six weeks, we start to space out those visits.  

I usually see my patients who are on active therapy about every three to six months to check and see whether they’re feeling okay, whether they’re having any side effects from the medicines, like I said to check their labs, make sure the medications aren’t causing any lab abnormalities. And also in the longer term, to make sure that their CLL is under good control on – on the medications. Because that’s one of our main goals is to keep the CLL under good control.  

Katherine Banwell:

We received another patient question prior to the program. Has there been any progress in helping CLL patients get a better reaction from COVID vaccines? 

Dr. Jean Koff:

That is a great question, and that is one that is near and dear to my heart and my colleagues at – at Emory. You raise a really good point, which is that CLL patients have altered immune systems just by virtue of their CLL. The CLL cells exert their influence on other immune cells and can cause your immune system not to respond to infections or immunizations the way it normally would. That’s without any medication in the mix. Now, when we look at patients who are on medications like the ones we’ve been talking about, the BTK inhibitors, venetoclax, but especially the monoclonal antibodies that react against CD20, we see that those patients really do not have an optimal response to vaccines, especially the COVID vaccine. 

Meaning, that patients who receive the COVID vaccine while they’re on that therapy, or even within twelve months of receiving a monoclonal antibody, often don’t mount the same strong immune response as somebody who’s not on those therapies. So, luckily, we – we don’t have to just depend on the vaccines. I still recommend that my patients get vaccinated, because it is safe and it might impart a little bit of efficacy, and it’s certainly more effective than not getting the vaccine. But we also have other approaches to increasing your protection against COVID, including the – the injection called Evusheld, which can help protect patients specifically whose immune systems are not completely normal and are not expected to mount a strong response to COVID vaccines.  

So, that is definitely a discussion to have with your doctor about how your medications impact your protection from COVID, from vaccines, and whether there are other medications that might be used to help increase your protection.  

Katherine Banwell:

That’s great advice. Dr. Koff I’d like to get your thoughts on where we stand with progress with helping people live longer and truly thrive with CLL. What would you like to leave the audience with? 

Dr. Jean Koff:

So, I think that one thing to remember with CLL is over the past few years we’ve seen an explosion in how we manage the disease because we have newer agents and therapeutic combinations that are helping people control their CLL for much longer than was possible 10 or 15 years ago. We still have a long way to go because ideally, we want every patient to be able to control their CLL and thrive with CLL for as long as possible. And, right now like I said before, we are not curing patients yet. Meaning that we don’t have a therapy that can get rid of the CLL, make it go away, and keep it away forever.  

That’s where clinical trials come in. That’s where we are able to make progress, is we’re able to study what therapies work, what therapies don’t, how they perform against each other, how they make patients feel, and what sort of side effects might be associated with them. And so, that’s really the next step, is continuing the work that has already been done in clinical trials and exploring these new therapeutical approaches. 

Katherine Banwell:

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

Dr. Jean Koff:

Thank you for having me. 

Katherine Banwell:

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

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What Could Boost COVID Vaccine Effectiveness in CLL Patients?

What Could Boost COVID Vaccine Effectiveness in CLL Patients? from Patient Empowerment Network on Vimeo.

Many patients with CLL worry about whether the COVID vaccine will be effective for them. Dr. Catherine Coombs explains how the vaccine works for CLL patients and available options to boost its efficacy. 

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

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Transcript:

Katherine:

COVID is of course another factor that impacts a patient’s ability to fully thrive with CLL in today’s world. Many CLL patients are concerned about the effectiveness of the COVID vaccines and their ability to make enough antibodies to fight the virus. So, what do we know about how effective the COVID vaccines are for people with CLL? 

Dr. Coombs:

The COVID vaccines – we were fortunate in being able to build on some earlier research. Even prior to being able to look at the data for COVID vaccines, there have been studies looking at vaccines in general in CLL. That’s actually been a long-term established issue, which is that based on earlier studies we knew most vaccines were not as efficacious in individuals with CLL compared to people without.  

That’s due to this underlying immune deficiency. Since then, they’ve done studies looking at COVID specifically, and we have found lower rates of production of antibodies in individuals with CLL compared to regular, non-CLL controls. There have been a few different studies looking at this. I think the things that have been seen universally is that the CLL patients that are the most severely affected are those that are actively on therapy or have had recent anti-CD20. The CD20 drugs really wipe out the ability to make antibodies probably for a year, if not up to two years.  

The other drug class that can really hamper the ability to make antibodies are these BTK inhibitors. Then, venetoclax to some extent, it’s often paired with the CD20, so it’s hard to tease out the effect. But it likely hampers the ability to make antibodies as well, but just not as much as the CD20, which it’s often given concurrently with.  

CLL patients who have never had therapy can make a decent amount of antibodies, but still quite a bit less than an age-matched control. So, someone also your age without CLL. That was a lot of data based on the original two vaccine series. The Leukemia & Lymphoma Society did a study that I actually referred a lot of my patients to, where they collected samples, looked at antibody levels, and they found that giving the booster did seroconvert a good amount of patients who were negative that then became positive for antibodies.  

That’s one of the reasons I’ve really encouraged the booster. This is now talking about the third shot. Now there’s this whole separate discussion about doing a fourth shot. I think the data’s a little too early to say it’s definitely helpful. But I think it’s certainly unlikely harmful. The vaccines don’t quite work as well. I feel very strongly they’re not harmful.  

Not to say any shot can’t cause some issue occasionally. But I think that’s very, very rare. I always encourage my patients to get the vaccine, but I separately say, “Gosh, I wouldn’t use this as an end-all cure because it may not work at its 100 percent efficacy level due to the underlying CLL, and worse when you’re under treatment.” 

Katherine:

We had another audience member send in a related question: “I’ve heard there is a treatment to help boost COVID antibodies. What is it, and how can I get access to it?” 

Dr. Coombs:

I was going to bring that up actually, then I figured there was probably another question coming. I’m hugely enthusiastic about the drug that this person is speaking about. It’s called Evusheld. E-V-U-S-H-E-L-D. It got this emergency use authorization designation in December of 2021, so it’s pretty new. The idea behind this drug is that “Gosh, we know that not everyone is going to mount an effective immune response to vaccines, based on their own immune system, inability to make good levels of antibodies.”  

So, it’s two antibodies that were manufactured as this drug. So, it’s a drug that’s actually two different antibodies. It ends up being in two different vials, so you get two shots. It provides really remarkable protection against COVID. They’re long-acting antibodies, so they last for six months.  

The publication from the study that led to this being released showed an approximately 80 percent reduction in COVID for the people who got the shot as opposed to the people who got the placebo.  

Katherine:

It sounds like patients could ask their doctors about where they might be able to access this? 

Dr. Coombs:

Yeah. I think the best person to ask would be your CLL doctor. Because the drug, unless things have changed recently, it’s largely being focused for immunosuppressed individuals. Primary care doctors may not necessarily know a lot about it, but most oncologists are the ones who should have access to it. So, I would say ask your CLL doctor. If you’re in a smaller site that doesn’t have it, they may know in your geographic region where it could be gotten. 

Expert Advice for CLL Self-Advocacy

Expert Advice for CLL Self-Advocacy from Patient Empowerment Network on Vimeo.

Some CLL patients struggle to find the confidence to speak up in their care. Dr. Catherine Coombs encourages patients to discuss their treatment and lifestyle goals with their CLL teams and provides advice for being proactive in their care.

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

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Transcript:

Katherine:

Dr. Coombs, why should patients feel confident in speaking up and being a partner in their care? Do you have any advice for helping them find their voice? 

Dr. Coombs:

Great question. I think a patient is their own best advocate. We as their physicians always try to advocate for them, but we often don’t know what their wishes and desires are. I think through speaking to what’s important to you, that can help me know a little more about what path we should take. There’s not always one right path.  

I’ve talked about these two great treatment options we have. I had one patient who loved fishing and he just didn’t want to be in the infusion center. That’s the person that should go on the oral drug, where he doesn’t have to come to and from as often.  

If you tell us about your goals and your desires, that helps us also be your top advocate because then we have a little more background for what’s important to you. I think that’s my main thought. We’re here for you, but we need to know what you value the most. We don’t always know that.  

Katherine:

When should a patient consider a second opinion or a consultation with a specialist? 

Dr. Coombs:

I never discourage a second option. I’m a CLL specialist, but I’ve had patients ask for a second opinion. I’m always enthusiastic about it. If a patient feels that they need another set of eyes on their case, I’ve learned some things from some of my patients who have seen specialists in different areas of the country or locally. We have Duke down the street. Sometimes different providers just have different perspectives.   

Or, sometimes the patient just needs to hear something again if it doesn’t sound right to them. I’ve had patients for example who are one watchful waiting who really just had trouble believing. “I have leukemia, and you’re really telling me to do nothing.” But then they hear it from someone else and it just helps it sink in. I’d say the answer is anytime. Anytime you think you need another set of eyes on the case.  

But I would say especially for people in the community. I do think there’s a lot of value in seeing a CLL specialist once if it’s something that you’re interested in and your insurance pays. I think the community docs have one of the hardest jobs, and I don’t think I could do it. There are so many different cancers that they have to know about. I think, if anything, I have the easy job; I have one tiny slice of the pie that I know a ton about. Not to say they don’t do great jobs; I’m actually phenomenally impressed with most of the community.  

However, they have so much to know, often you can maybe get a little more of a unique view on CLL by seeing a CLL expert. If that’s in your interest but certainly not mandatory, especially if your goal is to stay away from doctors.  

What Helps Determine a CLL Patient’s Treatment Options?

What Helps Determine a CLL Patient’s Treatment Options? from Patient Empowerment Network on Vimeo.

What guides a CLL treatment choice? Dr. Catherine Coombs discusses genetic mutations and factors that may help determine a CLL patient’s therapy .

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

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Transcript:

Katherine:

There’s not necessarily a one-size-fits-all approach to treating CLL, so how do you decide which treatment is right for a patient?  

Dr. Coombs:

I always look at their underlying disease biology. There’s a couple really important tests that I send for all of my CLL patients by the time that they need therapy. The first is to see what their underlying cytogenetics and molecular findings are. There are certain good findings, and then certain bad findings.  

One of the bad findings is having a deletion in the 17th chromosome in the short arm of that chromosome. The chromosomes are the big pieces of DNA within everyone’s cells. There are findings that are common in CLL: a 17p deletion is a poor prognostic feature. There’s a separate test where we can actually identify mutations in a gene called TP53. And these behave largely the same as 17p deletions, so I always check for both. It’s two different tests.  

Oftentimes patients have both of these findings: a 17p deletion and a TP53 mutation. But sometimes you can have the mutation without the deletion and vice versa. That is one finding that’s important when talking about different therapies. The other really important prognostic test is the IGHV gene mutation status. This is another specialized sequencing test. It looks to see if the patient’s heavy chain, if their immunoglobulin protein has undergone something called somatic hypermutation or not.  

It’s actually good to be mutated. What we know about people who are mutated is that they typically have better responses to most therapies and their disease typically is one that grows slower. So, I use those factors and then I have a conversation with the patient. The two main treatment classes that I spoke about – so the BTK inhibitors, those work actually really well and even the people with these bad prognostic features.  

So, people with the 17p deletion, people with the TP53 mutation, they can have disease control for six plus years on a BTK inhibitor, which is really good.  

That was not the case a decade ago when we didn’t have these drugs. That’s something that’s been hugely beneficial for our patients. The venetoclax/obinutuzumab regimen, that still works when people have the 17p or the TP53, but it probably doesn’t work as well.   

I’d mentioned the median time for disease to come back hadn’t been reached yet. It had been reached for that poor risk subset. The expectation for people with that poorest marker is that the median PFS, progression-free survival. So, again, when after someone starts therapy, when the disease then progresses is 49 months. It kind of gives me a rough estimate of, “Gosh, these are your therapy options and based on your underlying biologic factors unique to your disease, this is what you can expect out of therapy A or therapy B.”  

The mutated or unmutated IGHV, similarly, those BTK inhibitors work extremely well, even in people with the bad unmutated finding. I think those are always an option. The other treatment is an option, but the people with that bad finding do have a shorter time until they progress of just under five years.  

Refractory vs Relapsed CLL: What’s the Difference?

Refractory vs Relapsed CLL: What’s the Difference? from Patient Empowerment Network on Vimeo.

What is the difference between refractory and relapsed CLL? Dr. Catherine Coombs, a CLL expert from UNC Lineberger Comprehensive Cancer Center, explains.

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

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Transcript:

Katherine:

We received an audience question prior to the program. They asked, “What does it mean to be refractory, and how is that different from relapsing?” 

Dr. Coombs:

I actually just had a conversation about this. I’m not sure that’s formally defined. I have heard one definition suggested is – I think everyone agrees refractory means you did not respond to your last therapy. That’s actually really bad. Most of our therapies work in almost everyone. So, refractory is a term that is generally accepted means no response. So, whatever therapy you’re on, the CLL did not get better, it got worse. That’s refractory.  

Another definition that I’ve heard based on this recent discussion is if you had a short remission duration, such as six months or shorter. Most of the therapies we use should work for quite a while, usually on the order of years. So, some people also consider refractory a short remission duration, six months or shorter.  

Relapse is probably the more common scenario. That’s a patient who has had some type of therapy, but they had a decent response, but that response wore off, more on a normal pace. Again, not on the order of months, but usually on the order of years.  

Signs It Is Time to Treat Your CLL

Signs It Is Time to Treat Your CLL from Patient Empowerment Network on Vimeo.

When is it time to treat your chronic lymphocytic leukemia (CLL)? Dr. Catherine Coombs reviews the criteria doctors consider when deciding whether it is time to begin therapy. 

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

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Transcript:

Katherine:

When is it time to treat? What factors do you look at? 

Dr. Coombs:

There’s pretty well-established guidelines for when treatment is indicated. The international workshop for CLL has these published guidelines, so it’s something you could Google. Off the top of my head, the main reasons that I do treatment, which are included in these guidelines, are one, if the patient has low blood counts due to the CLL, so that could be anemia or low platelets. Two, if they have bulky lymph nodes. They actually define bulky as 10 centimeters. So, that’s pretty big.  

Or, if the lymph nodes are being symptomatic in some way, they’re bothering the patient, they don’t have to be that big. Three, if the patient has bulky spleen enlargement or if it’s causing symptoms. The spleen is next to the stomach. So, say some patients may not be able to eat a full meal, that’s another reason we could do treatment.   

Another reason is if the CLL is causing constitutional symptoms. Sometimes these are black and white. One is unintentional weight loss of 10 percent or more of the body weight. The one that’s not always black and white is fatigue. Patients can have fatigue from the CLL, but I’ve found often fatigue can be due to other causes. So, that’s something I consider an important job of mine is to make sure we don’t jump into CLL treatment if say, there’s some other cause for the tiredness, such as, say the thyroid’s off, or there’s a huge amount of stress due to some other factor outside of the CLL.  

Then, some other constitutional symptoms are CLL can cause fever or drenching night sweats. Those two it’s important to make sure that there’s not a concurrent infection because infections can also cause those symptoms. The last indication is patients with CLL can develop autoimmune cytopenias. That’s when the immune system attacks some component of the blood cells. Most commonly that’s an autoimmune anemia or autoimmune thrombocytopenia. That’s the term for low platelets.  

Usually, we can treat that with steroids or occasionally CD-20 by itself like rituximab to calm down the immune system. However, if those immune-based therapies fail the patient, then we could consider treating the CLL to help fix that problem.  

CLL Treatment Approaches: What Are the Types?

CLL Treatment Approaches: What Are the Types? from Patient Empowerment Network on Vimeo.

What treatment options are there for CLL patients? Dr. Catherine Coombs explains the types of CLL approaches available and who they may be appropriate for.

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

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Transcript:

Katherine:

Let’s walk through the types of treatments that are used today to treat CLL.  

Dr. Coombs:

So, for the non-watch-and-wait category, that means we are now thinking about therapy. Most of the time that involves a targeted agent.  

We largely are using a lot less in the way of cytotoxic chemotherapy. Not to say there isn’t a role for it, but in my own practice, it’s not something that I have been using in the past several years because it’s highly toxic. It is effective, but it can lead to some long-term toxicities. And it’s also not quite as effective as these new targeted agents. So, those fall into two major classes.   

The first class is a class of drugs called BTK inhibitors. That stands for Bruton’s tyrosine kinase. That’s an important target in the CLL cells, specifically. The CLL cells are a type of B cell. So, BTK is important for the signaling of both normal and cancerous B cells. When we use drugs to block that protein, that impairs the CLL cells’ ability to multiply. Then we ultimately are able to control the disease with prolonged administration of one of these drugs.  

There are two FDA-approved BTK inhibitors. The first FDA-approved agent is a drug called ibrutinib (Imbruvica). And then the newer agent is called acalabrutinib (Calquence). There’s another drug that you may have heard of called zanubrutinib (Brukinsa). That is not technically yet FDA-approved for CLL, but it is occasionally used given that it is FDA-approved for other lymphomas, and it is within the national cancer center network guidelines for CLL treatment.   

The big benefit of these drugs is they work phenomenally well at controlling the CLL. I would say the major downside is that they do have to be taken indefinitely. So, patients ask, “Am I going to be on it forever?” Well, it depends on what you mean by forever. We generally keep patients on these drugs as long as number one, they’re tolerating them, so no bad side effects, and then number two, as long as the CLL is staying under control.  

So, for that 85-year-old patient that I gave as an example, forever may be until the rest of their life. Because they can work for six, seven, eight plus years; so, they’re highly effective. Some patients may go on them and then die from something else years down the road. For the younger patients, or patients who progress faster, we would then put them on something else whenever the drug stopped working, provided that they didn’t have a significant side effect to the drug class. So, that’s a big first class.  

The second large subset of therapies is a drug called venetoclax (Venclexta), which we typically combine with an anti-CD20 drug. The one that we use for patients who are getting their first treatment is called obinutuzumab (Gazyva). Venetoclax is a BCL-2 inhibitor that inhibits this pathway within CLL cells. It’s not unique to CLL cells, but the CLL cells are particularly dependent upon it called apoptosis.  

So, when they get exposed to this drug, the CLL cells just die; they can’t continue living, they die off. So, venetoclax works really exquisitely well at killing off CLL cells. Probably works better when it’s paired with this drug obinutuzumab. That’s how it was approved in the frontline setting: those two drugs together. The big risk of that therapy, essentially, it’s kind of a weird risk, when the CLL cells die too quickly that can cause some problems in the human body because one has to metabolize all the debris left over from these dead cancer cells. The medical term we use for that is tumor lysis syndrome.  

That can actually be fatal if not done in a safe way. Fortunately, when we do it as per the recommendations by the manufacturer, we’ve not had any adverse severe problems from it. It ends up being that the patient has to come in weekly every five weeks to do a slow ramp-up of the drug to kind of slowly kill off the cancer cells so that the body isn’t overwhelmed by the contents of these dead cancer cells.  

The big advantage of this regimen is that because it kills the CLL so well, people can get into very deep remissions. So, instead of being a therapy that people are on indefinitely, it’s designed as a one-year therapy when given as the first therapy. So, it’s one year and then they’re done. People after that are in remission, they’re not on any treatment. They may feel like they don’t have CLL.  

Most of the time the CLL does come back. It depends on does the patient come back for something else? Which does happen when people are older. But it appears that it keeps people in remission for several years. The median, which is how long it takes for half of patients to have their disease come back, the median progression for survival has not yet been reached for the trial that was done using this therapy.  

So, that’s at least three, four plus years that we’ve been able to follow people. So, very attractive in that you’re done, and then you just wait for the disease to come back but largely feel good in the interim.  

Anxious From CLL Watch & Wait? How to Cope.

Anxious From CLL Watch & Wait? How to Cope. from Patient Empowerment Network on Vimeo.

Many CLL patients who are put on “watch and wait” following a diagnosis. Dr. Catherine Coombs explains this approach and provides advice on how patients can cope with the emotional impact of waiting to treat their disease. 

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

See More from Thrive CLL

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CLL Treatment Approaches: What Are the Types?

Signs It Is Time to Treat Your CLL

Signs It Is Time to Treat Your CLL

Refractory vs Relapsed CLL: What’s the Difference?

Transcript:

Katherine:

What would you say to a patient who has a lot of anxiety about having to wait for treatment? 

Dr. Coombs:

The first thing I would say is that anxiety is normal. More often patients are anxious than not because it’s really hard to be told you have a leukemia and that we’re not going to do anything about it. I think that’s really hard to hear. The way that I try to counsel people is that my role as the doctor is to do no harm. If you have a leukemia and there’s no proven way to make you live longer by giving therapy early on, if you’re in that early stage of CLL where you’re asymptomatic, by offering therapy, all I could do is make you worse.  

I could give you a new side effect, I could add a new cost burden. Until I have data to prove that that’s going to make your life longer, which we do not have yet (maybe that will be different five to 10 years from now, but we do not have that yet), I could only hurt you. So, that’s not what I want to do. I want to have you live and thrive.  

The better thing to do, based on what we know now and what we know our therapies can and can’t do is to do the watchful waiting. But the anxiety is normal. Depending on how severe the anxiety is, I have had patients meet with – at least at UNC we have something called the Cancer Center Support Program, which is a group of psychiatrists, psychologists, therapists that can help talk over what it means to have a cancer diagnosis and not necessarily need therapy.  

Then I also provide education on the other health issues that can come up as part of being a CLL patient even on that watchful waiting program. The thing that we talk about the most is the increased risk for infections, which in the era of the COVID pandemic is a major concern. Luckily, we have a lot of ways to decrease the health risk for COVID, whether it’s due to the administration of vaccines, or monoclonal antibodies, which I think we’ll talk about more later.  

There’re a lot of ways that people can live with it. I do think the anxiety is normal. At least in my own practice, I’ve found that most of the time the anxiety lessens with time. Because it becomes a part of who you are. It doesn’t have to be all of who you are: people can live their lives largely the way they did before with a bit of extra knowledge about things that can come up in the future but may never come up at all.