Tag Archive for: venclexta

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.  

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. 

What Myeloma Patients Should Know About Treatment Monitoring

What Myeloma Patients Should Know About Treatment Monitoring from Patient Empowerment Network on Vimeo.

How do you know if your myeloma treatment is working? Dr. Joshua Richter, a myeloma specialist, reviews how treatment response is measured in myeloma and why it’s important to share any symptoms or side effects with the healthcare team.

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

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Transcript:

Katherine:

So, once treatment has begun, how do you know if it’s working? 

Dr. Richter:

Absolutely. So, the majority of myeloma patients are what we call “secretory.” And by “secretory,” it means that the cancer cells secrete a protein that we can measure in the blood either an M-spike, which is an intact immunoglobulin like IgG and kappa, or a free light chain. It doesn’t make that IgG part, just a free kappa or free lambda. And basically, when these protein levels go up, we know the cancer cells are growing. When these go down, we know we’re killing the cancer cells. And we actually call your remission based on how much we lower it.  

If we lower it 25 to 49 percent, that’s an MR or minor response, or minor remission. 50 to 89 percent is a PR, partial response, partial remission. 90 to 99 percent is a VGPR, a very good partial remission, and then all gone in the blood and then we do a bone marrow is a CR or complete remission.  

For some people, their disease can be non-secretory where the cancer cells don’t make that protein anymore.  

And for those people, we need to do regular imaging to see if they have growths of myeloma we call plasmacytomas, or unfortunately, we need to do regular bone marrow biopsies to see how much of the bad cells are growing inside the marrow. 

Katherine:

All right. How do you know when it’s time to switch treatment? 

Dr. Richter:

So, in general, when patients fulfill the criteria for what we call “progressive disease” or PD, that’s the time to change, or intolerance that regardless of how we dose adjust, dose hold or add supportive care, it’s not tolerable for a patient to continue.  

Intolerance is a very personal thing. There are things that certain people are willing to tolerate and others not. So, we try to adjust that. Just like we have criteria for response, PR, VGPR, we have criteria for progression. And in general, it’s a 25 percent increase from your baseline and 0.5 increase in your M-spike or 100 increase in your light chains. So, when the disease numbers are going up, we tend to switch.  

Now, people may say, “But I feel fine,” and a lot of this is because you’re diagnosed with an amount of disease up here. We get you in remission, you’re down here. And once you go like this, we can see the writing on the wall and we’d rather be proactive than reactive. So, instead of waiting until the numbers get up here to cause trouble, once it goes from there to there, we intervene, change therapy to bring it back down. 

Katherine:

Dr. Richter, why is it essential for patients to share any issues they may be having with their healthcare team?  

Dr. Richter:

It is absolutely crucial because some things that may be very, very minor to them may be the tip of the iceberg of something very, very worrisome that we really need to investigate because sometimes, little problems are little now, and over time, they can become problems that we can’t so easily reverse. So, things like neuropathy, fatigue, or actually better yet, what I tell my patients is, “You know your body. If there is something out of the ordinary, big or small, let us know.”  

And I would way rather a patient tell me 10 things in a row that mean nothing than not tell me about that one thing that means something.  

So, for example, one of the disorders that’s associated with myeloma is called amyloidosis.  

And when amyloid attacks the kidneys, you start to have protein in the urine, and this looks like bubbles, like foam in the urine. So, if someone has no foam when they urinate, and then over a period of months to years, they’re starting to notice lots of foam, tell me because that means we may need to look for things like amyloid.  

So, really any time something changes.  

What Are Common Myeloma Treatment Side Effects?

What Are Common Myeloma Treatment Side Effects? from Patient Empowerment Network on Vimeo.

Myeloma specialist Dr. Joshua Richter reviews common side effects of myeloma treatment and strategies for managing them. 

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

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Transcript:

Katherine:

Can you help us understand some of the common issues that myeloma patients experience and how they might be managed? 

Dr. Richter:

Sure. So, fatigue is an absolutely huge one. And fatigue can come from a lot of different things. One, fatigue can come from other medicines. A lot of patients have cardiac issues and may be on other medicines causing fatigue. So, optimizing your other clinical status is important. Anemia can lead to fatigue, so we monitor your blood counts very closely, and if they drop, can we provide medicines to boost them up? Drugs. Some of the therapies we have can cause fatigue, and one of the biggest ones is Revlimid.  

And I tell people what actually tends to help is you take the Revlimid at night instead of the morning because if you take it at night, it tends to maximize the fatigue while you’re already sleeping. If you take it in the morning, it tends to maximize at that horrible, coffee-needing hour of 3:00 p.m. to 4:00 p.m., or 4:00 p.m. to 5:00 p.m. where you’re like, “Oh, I’ve gotta lie down.” So, fatigue is a really big one. Neuropathy. Neuropathy is really getting less and less in our new patients because more of our modern drugs don’t cause it, but unfortunately, some patients still have neuropathy, and they may be using drugs like gabapentin or Lyrica.  

There’s some other really old drugs and new drugs that can help. Drugs like Pamelor, which is nortriptyline, or Cymbalta may help quite a bit, or another drug called Effexor. And many of these drugs may be used for anxiety and depression, but also work for neuropathy. And then, even going to things like the cannabinoids; things like marijuana derivatives may actually be able to help both in salves or even edibles may actually help some of the neuropathy issues. And then, we get into some kind of out there stuff like compounding ketamine to help with some of these salves or oral combinations. So again, a little bit of neuropathy, let us know because there may be some ways to help.  

Key Factors That Guide Myeloma Treatment Decisions

Key Factors That Guide Myeloma Treatment Decisions from Patient Empowerment Network on Vimeo.

Treatment for myeloma varies from one patient to the next. Dr. Joshua Richter, a myeloma specialist, reviews the factors that are considered when choosing a treatment approach.

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

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Transcript:

Katherine:

What I would like to look at is because everyone’s different, what’s going to work for one patient might not work for another. So, how do you choose which treatment is right for a patient? 

Dr. Richter:

Really great question. So, unfortunately, myeloma, we don’t have the granularity just yet to say exactly what’s going to work for everyone. Our goal is to kind of be what I like to think of as urinary tract infections. You have a UTI, you pee on a dish, we put little discs of antibiotics and a couple of days later, we’re like, “You have an E. coli and Cipro will work.” You get the Cipro, and it goes way. We don’t really have that outside of a few drugs. We do know that the drug venetoclax works really well in people who have a very specific type of translocation in their myeloma cells, something we call translocation (11;14).  

But for the most part, we don’t know, and we have lots of options and we decide what drugs to use based on three factors: disease-related factors, treatment-related factors, patient-related factors. So, patient-related factors. Are you older or younger? Fit or frail? Do you have comorbidities? If you have a lot of neuropathy from diabetes, I don’t want to give you a drug that’s going to cause more neuropathy. If you have a lot of cardiac issues, I’m not going to give you a cardiac drug. Disease-related factors. Is your disease growing fast or slow? Can I give you some pills or do I need to give you intravenous immediately to stop it? Is it pressing on a nerve? Do I need to add radiation?  

So, those are some of the big factors. And then, treatment related factors. Have you had certain other drugs? So, if you’re refractory to Revlimid, I may not want to give you Revlimid again. 

If you have a lot of side effects or didn’t respond well to Revlimid, I may not want to use another drug similar to Revlimid like Pomalyst.  

I may want to choose another class. So, that’s kind of putting all of that together to come up with a treatment choice because there’s no clear guideline. 

Myeloma Research | CAR-T Cell & Bispecifics Study Updates

Myeloma Research | CAR-T Cell & Bispecifics Study Updates from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Joshua Richter reviews the latest updates in myeloma research from the 2022 American Society of Clinical Oncology (ASCO) annual meeting and the European Hematology Association (EHA) Congress.

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

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Updates in CAR T-Cell Therapy for Myeloma from ASH 2021


Transcript:

Katherine:

There were two major cancer meetings recently, ASCO and EHA. Are there research updates from those meetings that myeloma patients should know about?

Dr. Richter:

Absolutely. These are some of the biggest meetings that we have every year that attract all types of people, patients, caregivers, physicians, nurses, Pharma, even investors from all over the world. We’re coming off of the back-to-back American Society of Clinical Oncology and European Hematology Association meetings, and there were a couple of really important updates and data. One of them at ASCO actually had what we call a plenary session.

A plenary is the top type of session at any one of these congresses, and it was around something called the DETERMINATION trial which looked at something a lot of patients may be familiar with, the notion of getting VRd, Velcade, Revlimid, and dexamethasone, with or without getting a stem cell transplant as part of their initial treatment. Now, many years ago when our initial therapy was not so good, we showed that transplant was better than what was good 30 years ago.

But, we have better treatments now. So, do we still need high-dose chemotherapy and stem cell transplant?

And what was really interesting about this data set is that if you do get a transplant upfront, you do seem to have a longer PFS, progression-free survival, meaning you stay in remission longer if you get your transplant as part of your initial therapy. However, there was no difference in overall survival, meaning how long you actually lived. And this may not make a lot of sense at first, but think about patient one who stays in remission longer, but because now their disease is a little more refractory, the subsequent therapies don’t work as well as compared to the person who doesn’t get the transplant upfront.

And then those latter therapies work a little better, and when you add them all up, they come out about the same. So, I think one of the things that comes out of this is, “Do I need the transplant?” No, you don’t need the transplant as part of your initial therapy.

We’re still trying to figure out who really needs it and who doesn’t, but you can always never do it or save it for a later time. So, that was really one of the big things that came out of the ASCO meeting.

Katherine:

What about EHA?

Dr. Richter:

So, EHA had a lot of updates both in terms of CAR T-cell therapies and bispecific antibodies, and bispecific antibodies are near and dear to my heart. They’re my big passion in myeloma, and I had the honor of presenting updated data on the Regeneron 5458 bispecific antibody at EHA.

This is a BCMA CD3 bispecific. So, many people may be familiar with monoclonal antibodies like daratumumab, which is just an antibody that gets injected and attacks the cancer.

Bispecifics are molecules that are injected that have two arms. One grabs onto the cancer cell; the other grabs onto your own immune cells that we call T cells and activates them to attack the cancer. Very interesting new therapy.

Very exciting, and very high response rates in people who have had tons and tons of treatment. So, in people that have seen almost everything in the highest dosing group of the study, 75 percent of people responded, which is very, very high.

But more notably, the big side effect we look out for called CRS or cytokine release syndrome, that’s where we activate your T cells and they get so activated they can cause other problems. That can be pretty high in some of our immune therapies, but in this drug, there’s only 38 percent, and all of this was relatively minor. It wasn’t the really big stuff.

So, the reason why this is so near and dear to my heart is that some of these therapies like CAR T have to be given in a major center that does transplants.

But bispecific antibodies, if put together the right way, can be given in your local hematologist’s, oncologist’s office. So, a lot of great potential long-term get everybody treated with these drugs. And then, one or two other little things that I thought were really huge, one was the combining of bispecific antibodies. Studies called the TRIM protocols combined two different bispecific antibodies, one called teclistamab, and one called told talquetamab. Each got combined with daratumumab.

So, not only are we already seeing just the bispecific by itself, we’re starting to combine it and seeing unbelievable response rates. That was updated at EHA, which was groundbreaking. And then in CAR Ts, two things really caught my mind. One was the CARTITUDE-2 data basically giving CAR Ts earlier on to patients had a 100 percent response rate. Can’t really do better than 100 percent. So, it’s not just about getting 100 percent of people in remission.

It’s keeping them there and curing them, and it starts by getting 100 percent of people to respond. So, really looking forward to see how this develops.

But one of the other things was another CAR T that’s coming out of China that targets two different things. It targets BCMA and CD19, both of which can be found on myeloma cells, although CD19 is actually on the myeloma stem cell. It’s a little kooky. But one of the big issues with CAR Ts is manufacturing time. Right now, it takes four to eight weeks to make them. But in this construct, they were able to make them, it took them between 22 and 36 hours. So, for many people, they were able to manufacture the CAR Ts, theoretically, for patients within one day.

So, if we can not only get this therapy to work but shrink the manufacturing from a month or two to a day or two, that would make this more accessible to more patients, get them to their treatment on time. So, the sky’s the limit with our immune options right now.

Katherine:

What makes you hopeful? 

Dr. Richter:

So, we’ve had what we call Gestalt switches in myeloma. And what I mean by that is let’s rewind decades ago. We gave chemotherapy. Chemotherapy was designed to kill any cell that divides rapidly because that’s what cancer cells like to do.  

It kills the good and the bad. It makes your hair fall out, throw up, horrible stuff. It doesn’t work too well. Then about 20 years ago, we started this switch to the novel therapies, Revlimid, thalidomide, Velcade, and then a decade later, daratumumab. And now, we’re having targeted agents which spend more time targeting the bad stuff, less time doing off-target stuff, really ramping things up.  

We are at the precipice of a brand-new Gestalt switch in myeloma. The immune world. The immune therapies. And right now, T-cell redirection therapy is what we call it either with CAR-Ts, where we take your T cells out, engineer them, and put them back into your body all revved up, or we give you an off-the-shelf, bispecific that grabs onto your cancer and your T cell and, brace yourself, we even have trispecifics, which can engage your myeloma, another cell in your body, and yet another cell.  

If you go on clinicaltrials.gov, which lists all the trials for everything, every disease, there are over 3,000 active trials in myeloma.  

And what I tell people is when I first started and I sat across from a patient, I would say, “I’m really sorry. It’s not curable.” And now I say, “We are curing some people today by accident.” But over the next period of time, we’re going to do this deliberately and more frequently. And the goal is and always has been 100 percent of cure for 100 percent of patients, 100 percent of the time.  

And, I kind of feel right now we’re almost like that 2001: A Space Odyssey when the obelisk lands. We have these immune therapies. We know they’re great. How do we combine them? How do we use them? How do we take all these great tools and turn it into a cure for everyone?”   

And with so many great partners between advocacy groups and pharma and patients and cancer centers, we’re going to collaborate, and we’re going to start getting those answers in my lifetime, and I could not be more excited about that.   

Katherine:

Oh, I bet. I bet. 

CLL Research Highlights: What Should Patients Know About?

CLL Research Highlights: What Should Patients Know About? from Patient Empowerment Network on Vimeo.

What should CLL patients know about recent research updates? CLL expert Dr. Adam Kittai shares recent research highlights, including updates on BTK inhibitors, BCL-2 inhibitors, and monoclonal antibodies.

Dr. Adam Kittai is a hematologist and an assistant professor at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Kittai, here.

See More from CLL Clinical Trials 201

Related Resources:

How Can Clinical Trials Be Accessed?

Why Should CLL Patients Consider Participating in a Clinical Trial?

Clinical Trials As a CLL Treatment Option: What You Should Know

Transcript:

Katherine:

I understand that CLL researchers met recently at the annual American Society of Clinical Oncology meeting, also known as ASCO, to share their research. Are there highlights from the meeting that patients should know about?  

Dr. Kittai:

Yeah, so this time of year, there are two main conferences actually that are very important to the CLL groups at large, as well as the oncology community. So, there’s ASCO and then there’s EHA, the European Hematology Association. And in general, there was a lot of exciting things at both of these conferences. 

In CLL, we have two main treatments that we’re really focused on. One is called the BTK inhibitors, which is ibrutinib, acalabrutinib, and zanubrutinib that you may have heard about. And the other treatment regimen is called venetoclax, and that’s usually paired with something called obinutuzumab. So, right now we’re either using the BTK inhibitors or the venetoclax as our frontline therapies. And typically, when patients progress on either one of those treatments – their disease gets worse – we switch to the other one. 

And so, what I’m getting to be that right now, that paradigm of starting with one therapy – the BTK inhibitors or the venetoclax – and then switching to the other, or vice versa, is being challenged. How that’s being challenged is combining the two medications together to see if combining them together is better than giving them sequentially. So, I think this is the primary research that’s being looked at in the world of CLL and we got some updates to show that the combination of the BTK inhibitors, plus the venetoclax, is looking quite good. It’s looking like it’s inducing deep remissions in some of our patients.  

Some of the challenges here though that we still need to figure out is that a lot of these combinations are leading to more toxicity. So, ultimately, I think we’re going to have a discussion about who is the appropriate patient for the combination, as opposed to giving it sequentially. 

There’s also a lot more research going on, looking at what we call randomized trials, which we’ll get to in a second, to determine if the combination is better than giving it sequentially. Right now, we just have what we call single-arm studies that kind of show safety and how well the trial works. But really, the definitive clinical trials – and once again, we’ll get to this a little bit later – are going to be randomized study where we randomize patients to the combination versus the sequential therapy to determine if doing it together is better than doing it sequentially.  

So, I would say that this new treatment paradigm of combining our two main treatments up front is looking quite good. We’re worried about some of the toxicities when we combine these medications, and we’re still not quite sure if combining them is the right approach, if it actually is superior to giving them sequentially. So, I think that’s the name in research right now for CLL, whether or not combination therapy is better than sequential therapy. The jury is still out, but some of the new data we saw was exciting. 

Katherine:

So, how can patients stay up to date on research like this as it develops? 

Dr. Kittai:

Yeah, great question. So, for one, you can talk to your physician. A lot of the physicians will go to either ASCO or the European Hematology Association and be able to come back with some of this data to share with their patients. And then also, there’s a lot of smaller conferences that local oncologists will go to get highlights from these particular conferences, where they also will come back to the patient to let them know some of this highlighted research. I think that’s probably the easiest way for patients to get access to this research. And Google’s our friend, right? And so, a lot of things are available on Google if you know where to look for them. 

Clinical Trials As a CLL Treatment Option: What You Should Know

Clinical Trials As a CLL Treatment Option: What You Should Know from Patient Empowerment Network on Vimeo.

 Should you consider participating in a CLL clinical trial? In this webinar, Dr. Adam Kittai provides an overview of the clinical trial process and addresses common misconceptions. Dr. Kittai shares an update on the latest advances in CLL research and discusses key advice for patients considering trial participation.

Dr. Adam Kittai is a hematologist and an assistant professor at the The Ohio State University
Comprehensive Cancer Center – The James. Learn more about Dr. Kittai, here.

Download Guide

See More from CLL Clinical Trials 201

Related Resources:

What Helps Determine a CLL Patient’s Treatment Options

Setting CLL Treatment Goals WITH Your Team

Expert Advice for CLL Self-Advocacy

Transcript:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss the latest research advances in chronic lymphocytic leukemia and discuss the role of clinical trials in patient 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 program, you’ll receive a link a link to a program survey. This will allow you to provide feedback about your experience today and it will help us plan future webinars.  

Finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your health care team about what might be best for you. Okay, let’s meet our guest today. Joining me is Dr. Adam Kittai. Doctor, welcome. Would you please introduce yourself?  

Dr. Kittai:

Thanks for having me. My name is Dr. Kittai, I’m an Assistant Professor at the Ohio State University, and I specialize in research and clinical research in Chronic Lymphocytic Leukemia.   

Katherine:

Great. Thank you so much for taking the time to join us today.  

Dr. Kittai:

Happy to be here.  

Katherine:

I understand that CLL researchers met recently at the annual American Society of Clinical Oncology meeting, also known as ASCO, to share their research. Are there highlights from the meeting that patients should know about?  

Dr. Kittai:

Yeah, so this time of year, there are two main conferences actually that are very important to the CLL groups at large, as well as the oncology community. So, there’s ASCO and then there’s EHA, the European Hematology Association. And in general, there was a lot of exciting things at both of these conferences. 

In CLL, we have two main treatments that we’re really focused on. One is called the BTK inhibitors, which is ibrutinib, acalabrutinib, and zanubrutinib that you may have heard about. And the other treatment regimen is called venetoclax, and that’s usually paired with something called obinutuzumab. So, right now we’re either using the BTK inhibitors or the venetoclax as our frontline therapies. And typically, when patients progress on either one of those treatments – their disease gets worse – we switch to the other one. 

And so, what I’m getting to be that right now, that paradigm of starting with one therapy – the BTK inhibitors or the venetoclax – and then switching to the other, or vice versa, is being challenged. How that’s being challenged is combining the two medications together to see if combining them together is better than giving them sequentially. So, I think this is the primary research that’s being looked at in the world of CLL and we got some updates to show that the combination of the BTK inhibitors, plus the venetoclax, is looking quite good. It’s looking like it’s inducing deep remissions in some of our patients.  

Some of the challenges here though that we still need to figure out is that a lot of these combinations are leading to more toxicity. So, ultimately, I think we’re going to have a discussion about who is the appropriate patient for the combination, as opposed to giving it sequentially. 

There’s also a lot more research going on, looking at what we call randomized trials, which we’ll get to in a second, to determine if the combination is better than giving it sequentially. Right now, we just have what we call single-arm studies that kind of show safety and how well the trial works. But really, the definitive clinical trials – and once again, we’ll get to this a little bit later – are going to be randomized study where we randomize patients to the combination versus the sequential therapy to determine if doing it together is better than doing it sequentially.  

So, I would say that this new treatment paradigm of combining our two main treatments up front is looking quite good. We’re worried about some of the toxicities when we combine these medications, and we’re still not quite sure if combining them is the right approach, if it actually is superior to giving them sequentially. So, I think that’s the name in research right now for CLL, whether or not combination therapy is better than sequential therapy. The jury is still out, but some of the new data we saw was exciting. 

Katherine:

So, how can patients stay up to date on research like this as it develops? 

Dr. Kittai:

Yeah, great question. So, for one, you can talk to your physician. A lot of the physicians will go to either ASCO or the European Hematology Association and be able to come back with some of this data to share with their patients. And then also, there’s a lot of smaller conferences that local oncologists will go to get highlights from these particular conferences, where they also will come back to the patient to let them know some of this highlighted research. I think that’s probably the easiest way for patients to get access to this research. And Google’s our friend, right? And so, a lot of things are available on Google if you know where to look for them. 

Katherine:

Right. So, a key part in moving forward with CLL research is clinical trials, right? So, for people who may not know the term, what is a clinical trial? 

Dr. Kittai:

Yeah. So, a clinical trial is an experiment where patients are enrolled to receive a treatment that is either new or new in a new setting – so, an old treatment in a new setting – and we’re looking to see whether or not the treatment leads to improved outcomes for our patients.  

Katherine:

Why would a CLL patient consider participating in a trial? What’s the benefit for them? 

Dr. Kittai:

Yeah, great question again. The benefit of a clinical trial is two-fold. One is that by participating in a clinical trial, we are collecting data to determine what’s best for patients moving forward. [00:07:06] So, in a way, by participating in a trial, you’re contributing to the benefit of CLL patients in the future to help us determine what’s best for everybody moving forward. That’s one reason to go on a clinical trial. Another reason to go onto clinical trials is that it allows for access to therapies that may not be available otherwise, which may work better than what we already have and may be safer.  

Katherine:

Right. So, I’d like to walk through a few common questions that patients have about clinical trials. And here’s a concern we received from a patient prior to the webinar. “I’m nervous that I will receive a placebo if I join a clinical trial.” So, first of all, would you define a placebo?  

Dr. Kittai:

Sure. A placebo is usually a sugar pill or something that has no effect. That’s what a placebo is.  

Katherine:

And is it true then, would a patient possibly get a placebo in a CLL clinical trial? 

Dr. Kittai:

Not typically. So, in terms of clinical trials for CLL, we have a lot of treatments that are effective and safe in CLL. And so, we don’t typically design trials where you’re not getting some kind of active therapy. It would be extremely rare, and I don’t know of any trials currently that involve patients getting a placebo for CLL. Because it wouldn’t be ethical for us to enroll a patient on a trial where they would get a placebo instead of active therapy. 

Katherine:

Right. That makes sense. Here’s another question from an audience member, and I think this is probably a common concern for patients. “Is a clinical trial only something I should consider if there are no other options?” 

Dr. Kittai:

So, in my opinion, you should always consider a clinical trial, even if there are other options. And it’s because of those two reasons that I mentioned earlier. Number one, it benefits the CLL community as a whole to participate in the trial so that way doctors and researchers can collect data to improve outcomes for patients with CLL. And also, even though our drugs currently work really well, we don’t know how well they’ll last for, right? So, they still don’t know for certain how long our current drugs are going to work for in the future.  

And we’re always trying to do better. We’re always trying to create some sort of treatment, some sort of treatment paradigm that might be safer, as well as work better, and either of those goals is approvable. All of our drugs come with toxicity, right? And even though they’re really safe and they work really well, we’re hoping to develop something that is even safer and works even better.  

Katherine:

Yeah. It sounds, then, like trials can be considered throughout a patient’s life with CLL. What concerns do you hear from your patients?  

Dr. Kittai:

Yeah, so I think the primary concern I hear about a trial and the difference between going on a trial and standard of care, is that typically for a trial, it does require a little bit more from the patient. Meaning that there’s usually more visits – whether it is to monitor the effect of the new medication or new medication combination on the patient, whether or not it’s affecting their laboratory values or how they’re feeling.  

Or there might be parts of the trial that require invasive procedures. So, for instance, many trials will require bone marrow biopsies where a standard of care won’t. And the reason why the collection of those bone marrow biopsies is important for the trial is to better get an idea of how the treatment is working on a patient’s body.  

So, I think those are the two primary concerns I hear from the patient. Number one, it typically is a bigger time commitment with more visits to the doctor because we have to closely monitor the patients while they’re on trial. And number two is sometimes the trial involves procedures that otherwise wouldn’t be indicated for standard of care.  

Katherine:

Let’s talk a bit about how trials work, starting with the phases. What happens at each phase?  

Dr. Kittai:

There are actually four phases of clinical trials, although three phases are typically what’s talked about. So, Phase I is when we are first introducing the new medication, the combination, or the old medication in a new scenario for the first time in a human being.  

Phase one encompasses a lot of different things. It could be a first in-human phase one, where we’re giving the drug for the first time in a human being. It could be, as I said, the combination of drugs being used for the first time in a human being. Or it could be that we have this drug that works for this other cancer and we’re trying it out on this new cancer. So, we might have experience with this drug in another scenario, but not in the scenario we’re trying to do.  

And the primary purpose of the phase one clinical trial is to see if it’s safe. So, that’s the primary purpose of a phase one clinical trial – see if this new medication, this old medication in this new scenario, or this new combination is safe to use going forward.  

Katherine:

Right. 

Dr. Kittai:

We are able to see if it works to a small degree in the phase one trial, but typically these trials are very small with somewhere between 10 to 50 patients. And so, it’s hard to know how well this works by looking at such a small amount of patients.  

Once the Phase I trial goes forward, we usually go onto Phase II. So, one of the other points about Phase I is to determine the correct dose. Usually in phase ones, we increase the dose of the drug slowly until it meets some sort of toxicity cut-off for our patients. So, once that dose is discovered, then we move onto Phase II, and Phase II is usually a small study, usually about 50-100 patients where we’re looking at preliminary efficacy, to see if this drug, this new combination, or the drug in a new scenario, is actually working.   

And so, Phase II will tell us we think it’s working and if it looks good in phase two, it gets moved onto Phase III. Phase III is the final part of the drug development, where if it passes Phase III, it usually gets approved by the Federal Drug Administration. And Phase III is usually a randomized trial where you’re giving the new drug, the combo, or the old drug in a new situation, and you’re comparing it to whatever’s used as standard of care in that particular scenario.  

Katherine:

Right. 

Dr. Kittai:

And that’s usually a randomized study where patients are either getting the new thing or the old thing. And then, we’re determining which one works better. Lastly is Phase IV, and this is post marketing. So, after a drug gets approved, the drug company and the FDA requires just a wide scope of just data that’s collected to see how well the drug is working and if it’s safe once it’s brought out to the wider community.  

Katherine:

Okay. You mentioned randomized clinical trials. There are a couple of other clinical trials as well. Would you define them and tell us how they’re different from one another?  

Dr. Kittai:

Yeah. So, a randomized trial is when you enroll onto a study, and you get randomly assigned to either the experimental arm or the control arm. The experimental arm is that new drug that we talked about. And the control arm is usually the standard of care. So, that’s a randomized study. 

And randomized studies are usually Phase III trials, but they can be phase two in some scenarios as well. You have – usually that’s paired with a randomized control study. So, a control study is just there’s a control arm, that’s what that means. But those usually go hand in hand. Those are usually together.  

And then another trial is the double-blind clinical trial. So, a double-blind clinical trial means that once you’re randomized to either the experimental or the control, neither you nor the physician know what drug you’re taking. And that usually is not used in CLL trials. Usually, we know what drug the patient is assigned to. And the reason why that is, is because oftentimes we’re looking out for specific adverse events or toxicities of the drugs we’re implementing at Phase III.  

And then, also, if you’re getting a triplet versus a doublet, meaning three drugs versus two drugs, it’s very hard to blind somebody to know which drug they’re on because obviously you’re getting three drugs versus two drugs. Or if an infusion is involved in one arm but not in the other arm, you obviously know that you’re getting an infusion versus an oral drug. 

Katherine:

Ah, okay. Are there common clinical trial terms that you think patients should know about? 

Dr. Kittai:

I think we covered most of them. So, knowing that phase one is typically the first in the sequence of events that I would ask your physician if this was a first in human study, right, because that comes with some special considerations knowing that you are the first human to receive a new drug is very important. Versus a phase three study where, you know, you know this drug has already gone through phase one and two in development, meaning it’s been given to a lot of patients, and they’re just looking to see if it’s better than standard of care. So, I think knowing those general concepts about what’s the difference between a phase one and a Phase III study, it’s very different. I think it’s important to keep those in mind when talking about clinical trials and discussing with your doctor.  

Katherine:

Patients often have questions about safety. What are the risks of clinical trial participation?  

Dr. Kittai:

Yeah, so before anybody enrolls onto a clinical trial, you should sit with your doctor to talk about the pros and cons of entering this clinical trial. One of the things that they will talk to you about is what the expected safety of this drug is. So, you might ask yourself, well, if it’s a phase one study, first in human study, how do they know what toxicity to expect? 

Katherine:

Right. 

Dr. Kittai:

The answer is that there’s a lot of pre-human studies that occur, both in mice and monkeys and other animals, and researchers often have a good idea of what to expect in human. But there is a lot of unknowns in a phase one clinical trial. And after discussing with your doctor the pros and cons of going on a clinical trial and what side effect profile to expect from whatever drug or combination that you are about to be using, usually you go through a consent.  

Usually, you’ll get a packet, it’s about 10 to 20 pages long, written in a way that patients can understand. And it’ll have a list of toxicities that are associated with the research that is occurring. In terms of knowing what adverse events might happen, the consent is key, because it’ll have those all listed out.  

And also having the conversation with your physician about either what they’ve experienced giving this clinical trial, or what is to be expected after this drug had been introduced pre-humans.  

Katherine:

Mm-hmm. Are there protocols in place to protect patients? 

Dr. Kittai:

Yes. So, remember how we talked about in the phase one trials, we dose escalate the drug until we’ve reached some toxicity limit? There are specifically rules written out in a protocol that the doctor must follow that ensures safety for the patients that enroll in clinical trials. And that dose escalation part where we reach a toxic limit is a key part of those phase one trials that is spelled out before you even enroll.  

Usually, there’s also something called a Data Safety Monitoring Committee, as well as other committees that are looking at patients as they are receiving these drugs and move forward on clinical trials to make sure that the investigators are following the protocol as printed. That if anything happens, they document why it happened and fix the problem before it becomes another problem for a patient. So, there are very specific safety rules and a lot of redundancy to protect our patients, because the number one priority is to protect the patient. 

Katherine:

Yeah. I think you’ve already answered this, Dr. Kittai, but how do you know the medicine is safe before a human trial even begins? 

Dr. Kittai:

The answer is you don’t. There is some risk. As I said, they do test it in animals before they give the drug to humans, and they usually start at the lowest dose possible. But there are certain circumstances where there are surprising side effects that are not expected. And so, when you’re entering a first in human, Phase I trial, that is a specific risk that you do need discussed with your physician about before you enroll. 

Katherine:

Can a patient change their mind once they’ve enrolled in a clinical trial? 

Dr. Kittai:

Always. Always.  

Katherine:

Okay. 

Dr. Kittai:

They can come off the clinical trial at any point if they choose to.  

Katherine:

Okay. Now that we know what trials are and how they work, how can people find out what trials are available to them? 

Dr. Kittai:

Yeah. So, I’ll come back to this, but once again, talk to your physician. They’ll know what clinical trials are available at whatever site you are seeing them in. If there’s a local academic sector, the academic sector typically has clinical trials available there as well. So, it’s always good to get a second opinion in that regard.  

But one of the open access places that you can find all clinical trials is clinicaltrials.gov. This has all active running clinical trials listed out and anyone can access it. There are other societies out there that often post about clinical trials. So, there’s the CLL Society. It’s a website that you can check out that has a lot of information on there about active clinical trials in CLL. There’s also The Leukemia & Lymphoma Society, the Lymphoma Research Foundation, they all have websites available that have a lot of clinical trials listed and how to access them.  

Katherine:

Are there key questions that you think patients should ask their health care team about participating in a trial?  

Dr. Kittai:

Yeah, for sure. I think one of the key questions to ask is, is the control arm appropriate. So, what do I mean by that? Sometimes people who design a clinical trial will design a trial where the control arm is an easy control arm to beat, meaning that it’s a treatment that we wouldn’t necessarily put you on as standard of care.  

And so, I think this is a real question and an honest question that you should ask your physician prior to enrolling on a trial is, is the control arm something you would give me as standard of care. And if the answer is no, you should really consider not going on that trial or talking about why you would want to go on that trial if the control arm is not something they would put you put you on as standard of care.  

Katherine:

Right. 

Dr. Kittai:

That’s, I think, a key question to ask. And again, asking what phase it is and understanding where we are in the development.  

Katherine:

What do you feel are the barriers to accessing clinical trials for patients?  

Dr. Kittai:

So, unfortunately, a lot of clinical trials are at academic centers, and so there are – and the reason that is, is that the academic centers have the infrastructure to run the clinical trial. So, as we have mentioned before, there’s a lot of visits with a lot of extra science and labs that are done associated with the clinical trial. And a lot of those things and the coordination can only be done at large centers that can open clinical trials and know how to run them.  

Similar explanation could be that that safety monitoring committee that I’d mentioned before, where the academic centers have the infrastructure to ensure safety for the patients. So, access to academic centers is a limitation to enrolling in clinical trials. That being said, there are a lot of centers that are associated with an academic center and do have a lot of the clinical trials that are available at the academic center.  

And there are also cooperative groups. These cooperative groups are called Alliance and ECOG and SWOG. And these cooperative groups are national groups that are headed by multiple academic centers in partnership with pharmaceutical companies and they typically run large Phase III medical trials that help redefine standard of care. And those particular clinical trials are often available at private practices as well.  

Katherine:

Oh, that’s great. So, patients don’t necessarily have to think about traveling to a large educational institution then to become part of the clinical trial?  

Dr. Kittai:

Not always. Not always. Typically for the Phase I, the answer is yes. But for Phase III trials, usually there’s a lot of access available for Phase III trials.  

Katherine:

What would you say to patients who may be hesitant about participating in a trial?  

Dr. Kittai:

I would say that it’s important to at least ask about what’s available. And knowing what’s available and the risks and benefits of going on a clinical trial is how you should make the determination if you should go on a clinical trial.  

Remember what I said earlier that the clinical trial is really meant to help improve safety or efficacy. So, we don’t open clinical trials that we are not hoping to improve one of those two things. And so, that is something that we should be able to put in words to you when inquiring about the clinical trial. What is the goal of this trial, and why do you think it’s going to improve safety or efficacy? And the physician who’s talking the trial with you about it should be able to answer those questions for you. So, if you have some hesitance about going in clinical trials, I would say gather your information first before making a final decision.  

Katherine:

Some patients worry about the financial aspect or impact of a clinical trial. Aren’t trials expensive?  

Dr. Kittai:

So, actually, most clinical trials are less expensive than enrolling a standard of care. So, this is actually a benefit of going on a clinical trial. Often times, the drugs in the clinical trial are a cover. So, that’s something to ask too. And so, if somebody’s having trouble getting access to novel therapy that is looking good in a specific cancer, a clinical trial is actually a way to get access to that drug without paying for it.  

Also, all clinical trials when they’re being developed are looked at by the finance committees of the hospital or wherever it’s being developed. All standard of care options are billed through the patient insurance, but all the extra stuff is usually covered by the pharmaceutical company that’s enrolling those patients onto the trial. Or I should say the supporting the clinical trial, excuse me. 

Katherine:

That’s really good information to have.  

We touched on research at the top of the program, but are there other areas of research that you’re excited about and that patients should know about? 

Dr. Kittai:

Yeah, so one of the things that I think is being really talked about in cancer care – and medical care in general – is if disparities exist between minority patients and white patients. And I think this is a really, really important topic.   

So, the American Society of Clinical Oncology, which had the conference recently, really made this a mainstay point of the conference this year and there were a lot of abstracts that were defining whether disparities exist and hopefully, by defining whether disparities exist, we’re able to target those disparities in order to make outcomes equal for all of our patients.  

So, in the CLL world, one of the things that I alluded to is a lot of our therapies can be really expensive. So, these new therapies are really expensive, they really widen the disparity gap for patients who are minorities, as well as patients who come from socioeconomic status.  

Katherine:

Absolutely. 

Dr. Kittai:

And so, there were two abstracts. One was an oral presentation that looked at the National Cancer Database in ASCO that showed that Black patients do have worse overall survival than white patients. And then, I actually did my own study looking at the SEER database, which also showed the same exact thing. Even when controlling for socioeconomic status.  

So, I think addressing these disparities, making sure that there’s equity amongst our patients, that everyone has access to these drugs and can afford them, especially when they make our patients live longer and are safer than chemoimmunotherapy in CLL is very, very important.  

Katherine:

Dr. Kittai, if a patient feels like they’re not getting equitable care, are there resources available for them?  

Dr. Kittai:

Yeah, so one of the things that I love about the CLL society, is that they have a section called Access an Expert, I believe. So, look on the website, I’m not sure it’s actually called Access an Expert, but it’s a way for all patients to get a second opinion from one of the CLL experts listed on the website. And so, if somebody is feeling like they’re not getting access to the most beneficial treatment, for whatever reason, seeking a second opinion and using the CLL Society’s website to find that second opinion, I think would be a great way for someone who feels that way to get access to the care that they deserve.  

I believe there are other ways to do this through the Lymphoma Research Foundation, as well as LLS. But I know for sure on the CLL Society, there is a link that you can click that you can get access to a second opinion.  

Katherine:

Yeah. I’m glad you brought that up. As we wrap up the program, Dr. Kittai, I’d like to get your final thoughts. What message do you want to leave the audience with related to clinical trial participation?  

Dr. Kittai:

Yeah. So, I would say that in the last ten years, there’s been a revolution in the way we treat CLL, and we wouldn’t have gotten here without clinical trials. So, the reason why we have the BTK inhibitors – the ibrutinib, acalabrutinib, and zanubrutinib – and the reason why we have the BCL-2 Inhibitor venetoclax, and the reason why these have changed the way that we treat CLL making our patients live longer with better safety profiles is because of clinical trials. And so, I am a firm believer that if we can enroll a patient onto a clinical trial that’s appropriate, who might benefit from the trial, then they should enroll in the clinical trial if possible.  

So, I strongly encourage everybody to enroll onto clinical trials, to get access to, you know, groundbreaking new therapies. And once again, I want to highlight that the point of a clinical trial is to improve safety or to improve efficacy and that’s why we develop clinical trials and that’s the hope by running it.  

Katherine:

Okay, that’s great advice. Dr. Kittai, thank you so much for joining us today. It’s been a pleasure.  

Dr. Kittai:

Yeah, it’s been a pleasure to you. Happy to be here. 

Katherine:

Thank you.  

And thank you to all of our partners. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this webinar. It will help us as we plan programs in the future.  

To learn more about CLL and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today. 

Thriving With Myeloma: What You Should Know About Care and Treatment

Thriving with Myeloma: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

What does it mean to thrive with myeloma? Myeloma specialist and researcher, Dr. Joshua Richter discusses the goals of myeloma care, reviews treatment options –including research updates – and shares tools for taking an active role in decisions.

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

Download Guide

See More from Thrive Myeloma


Related Programs:

How Could Clinical Trials Fit Into Your Myeloma Treatment Plan?

How Could Clinical Trials Fit Into Your Myeloma Treatment Plan?

The Latest in Myeloma Research: Updates from ASH 2021

The Latest in Myeloma Research: Updates from ASH 2021

Updates in CAR T-Cell Therapy for Myeloma from ASH 2021

Updates in CAR T-Cell Therapy for Myeloma from ASH 2021


Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today’s webinar is about how to live and thrive with myeloma. We’re going to discuss myeloma treatment goals and how you can play an active role in your care. Before we meet our guest, let’s review a few important details. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Let’s meet our guest today. Joining me is Dr. Joshua Richter. Dr. Richter, welcome. Would you please introduce yourself?

Dr. Richter:

Hi. Thank you for having me today. My name is Joshua Richter.

I’m an associate professor of medicine at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai and the director of myeloma at the Blavatnik Family Chelsea Medical Center of Mount Sinai.

Katherine:

Great. Thank you for taking the time to join us today. There were two major cancer meetings recently, ASCO and EHA. Are there research updates from those meetings that myeloma patients should know about?

Dr. Richter:

Absolutely. These are some of the biggest meetings that we have every year that attract all types of people, patients, caregivers, physicians, nurses, Pharma, even investors from all over the world. We’re coming off of the back-to-back American Society of Clinical Oncology and European Hematology Association meetings, and there were a couple of really important updates and data. One of them at ASCO actually had what we call a plenary session.

A plenary is the top type of session at any one of these congresses, and it was around something called the DETERMINATION trial which looked at something a lot of patients may be familiar with, the notion of getting VRd, Velcade, Revlimid, and dexamethasone, with or without getting a stem cell transplant as part of their initial treatment. Now, many years ago when our initial therapy was not so good, we showed that transplant was better than what was good 30 years ago.

But, we have better treatments now. So, do we still need high-dose chemotherapy and stem cell transplant?

And what was really interesting about this data set is that if you do get a transplant upfront, you do seem to have a longer PFS, progression-free survival, meaning you stay in remission longer if you get your transplant as part of your initial therapy. However, there was no difference in overall survival, meaning how long you actually lived. And this may not make a lot of sense at first, but think about patient one who stays in remission longer, but because now their disease is a little more refractory, the subsequent therapies don’t work as well as compared to the person who doesn’t get the transplant upfront.

And then those latter therapies work a little better, and when you add them all up, they come out about the same. So, I think one of the things that comes out of this is, “Do I need the transplant?” No, you don’t need the transplant as part of your initial therapy.

We’re still trying to figure out who really needs it and who doesn’t, but you can always never do it or save it for a later time. So, that was really one of the big things that came out of the ASCO meeting.

Katherine:

What about EHA?

Dr. Richter:

So, EHA had a lot of updates both in terms of CAR T-cell therapies and bispecific antibodies, and bispecific antibodies are near and dear to my heart. They’re my big passion in myeloma, and I had the honor of presenting updated data on the Regeneron 5458 bispecific antibody at EHA.

This is a BCMA CD3 bispecific. So, many people may be familiar with monoclonal antibodies like daratumumab, which is just an antibody that gets injected and attacks the cancer.

Bispecifics are molecules that are injected that have two arms. One grabs onto the cancer cell; the other grabs onto your own immune cells that we call T cells and activates them to attack the cancer. Very interesting new therapy.

Very exciting, and very high response rates in people who have had tons and tons of treatment. So, in people that have seen almost everything in the highest dosing group of the study, 75 percent of people responded, which is very, very high.

But more notably, the big side effect we look out for called CRS or cytokine release syndrome, that’s where we activate your T cells and they get so activated they can cause other problems. That can be pretty high in some of our immune therapies, but in this drug, there’s only 38 percent, and all of this was relatively minor. It wasn’t the really big stuff.

So, the reason why this is so near and dear to my heart is that some of these therapies like CAR T have to be given in a major center that does transplants.

But bispecific antibodies, if put together the right way, can be given in your local hematologist’s, oncologist’s office. So, a lot of great potential long-term get everybody treated with these drugs. And then, one or two other little things that I thought were really huge, one was the combining of bispecific antibodies. Studies called the TRIM protocols combined two different bispecific antibodies, one called teclistamab, and one called told talquetamab. Each got combined with daratumumab.

So, not only are we already seeing just the bispecific by itself, we’re starting to combine it and seeing unbelievable response rates. That was updated at EHA, which was groundbreaking. And then in CAR Ts, two things really caught my mind. One was the CARTITUDE-2 data basically giving CAR Ts earlier on to patients had a 100 percent response rate. Can’t really do better than 100 percent. So, it’s not just about getting 100 percent of people in remission.

It’s keeping them there and curing them, and it starts by getting 100 percent of people to respond. So, really looking forward to see how this develops.

But one of the other things was another CAR T that’s coming out of China that targets two different things. It targets BCMA and CD19, both of which can be found on myeloma cells, although CD19 is actually on the myeloma stem cell. It’s a little kooky. But one of the big issues with CAR Ts is manufacturing time. Right now, it takes four to eight weeks to make them. But in this construct, they were able to make them, it took them between 22 and 36 hours. So, for many people, they were able to manufacture the CAR Ts, theoretically, for patients within one day.

So, if we can not only get this therapy to work but shrink the manufacturing from a month or two to a day or two, that would make this more accessible to more patients, get them to their treatment on time. So, the sky’s the limit with our immune options right now.

Katherine:

Excellent. Since this webinar is part of Patient Empowerment Network’s Thrive series, I thought we could start by getting your opinion on what you think it means to thrive with myeloma.

Dr. Richter:

Absolutely. And I love that term. I recently chaired a 5K walk for the MMRF, and the word that is thrown around a lot in cancer is “survivorship.” And, I got up there and I said, “That’s not a word I like to use. I like to use the word “thrivorship.” So, I love that you’re using this word because to me, surviving is an important part of dealing with cancer, but it’s the first step. Thriving is the goal. The goal is not to just get through it. It’s to go beyond it. It’s to do everything you want to do in life: personal, family, business, anything you want.

If you want to spend your time fishing, if you want to spend your time skydiving, if you want to spend time with your grandkids, and enjoying that time, and as much as humanly possible, keeping the notion of cancer way out of your brain. To me, that is thriving and not just surviving with a diagnosis like myeloma.

Katherine:

That helps us guide through the conversation as we continue on. Getting the appropriate myeloma care is, of course, part of thriving. So, let’s talk about treatment. How would you define treatment goals?

Dr. Richter:

Sure. So, treatment goals are different for each different individual because unfortunately, myeloma tends to affect people who are older. So, whereas the goals for an 85 or 90-year-old diagnosed with the disease is maybe things like, “I don’t want to suffer. I don’t want to have as many side effects,” but the goal is not to live 40 years, that’s different from a 40-year-old who may say, “I’m willing to tolerate certain side effects because I want to live as far as possible.” So, in reality, there always has to be this huge balance. And as with anything in medicine, an open dialogue with your care team is crucial to understand what your goals are because a lot of us make assumptions on both sides.

The patient may assume that we want certain things out of this. We may assume the patient wants certain goals. Really open, vibrant discussions where there are no taboos, there’s nothing wrong to say. I’ve had patients say, “I don’t care what happens. My granddaughter is getting married next year. I need to be there.

Anything beyond that, I don’t care.” That’s their goal. They’re entitled to their goal. I will work with them within that construct. So, really being open about what the goals are. Right now, what I tell patients is, especially for younger patients who if you’re already 85 or 90, you’re getting closer and closer to how long you’re likely to survive even without myeloma.

It’s kind of hard to have a 90-year-old have a 30-year survival. We’re not living to 120 just yet anyway. But for most of my patients, I say my goal is to either keep you in remission so long that you pass from something else many years from now, or to keep you moving until we have a cure that we can just give you and then make sure that that cure, that you’re able to accept it. That your body’s intact, your bone marrow’s contact, and this is something we can provide for you.

Katherine:

Well, tell me what you think the patient’s role is, then, in setting care goals.

Dr. Richter:

Absolutely. The patient has the most crucial role of course. And, one of the things is honesty and really being to a point of brutal honesty with how they’re doing. I always tell patients, “You don’t get extra points for suffering. It’s not that if you sit there in pain you’re going to do better. Let me know what type of pain you’re having.” And pain doesn’t just mean a bone is hurting, or a muscle’s hurting, we call somatic pain.

There can be neuropathic pain where the nerves hurt.

There can be emotional and spiritual pain. These things all need to be addressed. And if you are suffering in silence, we have a lot of tools nowadays not just medicines. We have people to talk to. We have resources. So, letting us in to help is one of the most crucial things because we’ve actually shown that if you actually improve some of these, you may actually improve overall outcomes. So, the patient, please, all we want to do on the care side of the equation is help.

Let us know what’s bothering you. It may be small to you, it may be big to us, or vice versa, but the more open you are, the better we can help.

Katherine:

Yeah, that’s great advice. Before we move on to discussing how the treatment choice is determined, let’s define a couple of terms that are often mentioned in myeloma care. What does it mean to be refractory and how is that different from relapsing?

Dr. Richter:

Great question. So, these terms have very specific definitions in myeloma. “Relapsing” just means that the disease is coming back. So, you had myeloma that was measurable, you went into a remission, and now it is showing signs that it’s coming back. We call that “relapsing.” And depending upon what type of myeloma, we have specific definitions. So, if you’re IgG kappa and you make an M-spike, if your M-spike goes up at least 0.5 and at least 25 percent, we call that “relapsing.” If you’re a light chain, it’s gotta go up by at least 100. But, you’ve gotta make sure the units are right.

“Refractory” means that you either did not respond or you’re progressing on or within 60 days of your last treatment. So, I put you on Revlimid maintenance, and you’re on Revlimid, and your disease gets worse. You are now relapsed and refractory to Revlimid. If I give you a transplant and then I put you on nothing, and two years later your disease comes back, you’re relapsed but not refractory.

Katherine:

What I would like to look at is because everyone’s different, what’s going to work for one patient might not work for another. So, how do you choose which treatment is right for a patient?

Dr. Richter:

Really great question. So, unfortunately, myeloma, we don’t have the granularity just yet to say exactly what’s going to work for everyone. Our goal is to kind of be what I like to think of as urinary tract infections. You have a UTI, you pee on a dish, we put little discs of antibiotics and a couple of days later, we’re like, “You have an E. coli and Cipro will work.” You get the Cipro and it goes way. We don’t really have that outside of a few drugs. We do know that the drug venetoclax works really well in people who have a very specific type of translocation in their myeloma cells, something we call translocation (11;14).

But for the most part, we don’t know, and we have lots of options and we decide what drugs to use based on three factors: disease-related factors, treatment-related factors, patient-related factors. So, patient-related factors. Are you older or younger? Fit or frail? Do you have comorbidities? If you have a lot of neuropathy from diabetes, I don’t want to give you a drug that’s going to cause more neuropathy. If you have a lot of cardiac issues, I’m not going to give you a cardiac drug. Disease-related factors. Is your disease growing fast or slow? Can I give you some pills or do I need to give you intravenous immediately to stop it? Is it pressing on a nerve? Do I need to add radiation?

So, those are some of the big factors. And then, treatment related factors. Have you had certain other drugs? So, if you’re refractory to Revlimid, I may not want to give you Revlimid again. If you have a lot of side effects or didn’t respond well to Revlimid, I may not want to use another drug similar to Revlimid like Pomalyst.

I may want to choose another class. So, that’s kind of putting all of that together to come up with a treatment choice because there’s no clear guideline.

Katherine:

Right. Can you help us understand some of the common issues that myeloma patients experience and how they might be managed?

Dr. Richter:

Sure. So, fatigue is an absolutely huge one. And fatigue can come from a lot of different things. One, fatigue can come from other medicines. A lot of patients have cardiac issues and may be on other medicines causing fatigue. So, optimizing your other clinical status is important. Anemia can lead to fatigue, so we monitor your blood counts very closely, and if they drop, can we provide medicines to boost them up? Drugs. Some of the therapies we have can cause fatigue, and one of the biggest ones is Revlimid.

And, I tell people what actually tends to help is you take the Revlimid at night instead of the morning because if you take it at night, it tends to maximize the fatigue while you’re already sleeping. If you take it in the morning, it tends to maximize at that horrible, coffee-needing hour of 3:00 p.m. to 4:00 p.m., or 4:00 p.m. to 5:00 p.m. where you’re like, “Oh, I’ve gotta lie down.” So, fatigue is a really big one. Neuropathy. Neuropathy is really getting less and less in our new patients because more of our modern drugs don’t cause it, but unfortunately, some patients still have neuropathy and they may be using drugs like gabapentin or Lyrica.

There’s some other really old drugs and new drugs that can help. Drugs like Pamelor, which is nortriptyline, or Cymbalta may help quite a bit, or another drug called Effexor. And, many of these drugs may be used for

anxiety and depression, but also work for neuropathy. And then, even going to things like the cannabinoids; things like marijuana derivatives may actually be able to help both in salves or even edibles may actually help some of the neuropathy issues. And then, we get into some kind of out there stuff like compounding ketamine to help with some of these salves or oral combinations. So again, a little bit of neuropathy, let us know because there may be some ways to help.

Katherine:

Are kidneys impacted by any of the medications that patients take?

Dr. Richter:

So, kidneys are an excruciatingly important part of myeloma, and d in my mind, one of the keys to long-term survival and outcome. So, there are three things that I tell all of my patients to help preserve long-term kidney health. Two of them are easy to wrap the head around. One is a little bit harder. Number one, keep yourself well hydrated. The kidneys are like a filter. Think, like, the filter for your car. If you drove 100,000 miles in the desert and didn’t change your oil, there’d be problems. So, especially now that there’s warmer weather, by the time you already feel yourself dehydrated, you’re about 10 to 15 percent low on the total amount of body water you need.

So, especially if you’re going out there doing yard work, playing with the kids or grandkids, make sure you’re drinking plenty of water. Two, avoid NSAIDs. Drugs like Aleve, or naproxen, or Advil, or ibuprofen can be harmful to the kidneys. So again, please discuss with your care team. There may be better alternatives to treat your pain without hurting the kidneys. And the third is when all else possible, and avoid intravenous contrasts for CAT scans. Now, the IV contrast you get for MRIs is called gadolinium. It’s not harmful to the kidneys. But, the contrast for CAT scans is iodine-based, and although the newer formulations are better, it can still hurt the kidneys.

So, my advice is the following. If you’re in the ER at 2:00 a.m. in the morning and they want to do an urgent CAT scan with IV contrast, let them do it. It’s likely not going to be an issue. If you go to see an orthopedist and they say, “I want to get a better look at that leg that’s bothering you. I’m going to get a CAT scan with IV contrast,” tell them to call me. We’ll find an alternative.

Katherine:

Okay. All right. Good advice. Thank you. So, once treatment has begun, how do you know if it’s working?

Dr. Richter:

Absolutely. So, the majority of myeloma patients are what we call “secretory.” And by “secretory,” it means that the cancer cells secrete a protein that we can measure in the blood either an M-spike, which is an intact immunoglobulin like IgG and kappa, or a free light chain. It doesn’t make that IgG part, just a free kappa or free lambda. And basically, when these protein levels go up, we know the cancer cells are growing. When these go down, we know we’re killing the cancer cells. And we actually call your remission based on how much we lower it.

If we lower it 25 to 49 percent, that’s an MR or minor response, or minor remission. 50 to 89 percent is a PR, partial response, partial remission. 90 to 99 percent is a VGPR, a very good partial remission, and then all gone in the blood and then we do a bone marrow is a CR or complete remission.

For some people, their disease can be non-secretory where the cancer cells don’t make that protein anymore.

And for those people, we need to do regular imaging to see if they have growths of myeloma we call plasmacytomas, or unfortunately, we need to do regular bone marrow biopsies to see how much of the bad cells are growing inside the marrow.

Katherine:

All right. How do you know when it’s time to switch treatment?

Dr. Richter:

So, in general, when patients fulfill the criteria for what we call “progressive disease” or PD, that’s the time to change, or intolerance that regardless of how we dose adjust, dose hold or add supportive care, it’s not tolerable for a patient to continue.

Intolerance is a very personal thing. There are things that certain people are willing to tolerate and others not. So, we try to adjust that. Just like we have criteria for response, PR, VGPR, we have criteria for progression. And in general, it’s a 25 percent increase from your baseline and 0.5 increase in your M-spike or 100 increase in your light chains. So, when the disease numbers are going up, we tend to switch.

Now, people may say, “But I feel fine,” and a lot of this is because you’re diagnosed with an amount of disease up here. We get you in remission, you’re down here. And once you go like this, we can see the writing on the wall and we’d rather be proactive than reactive. So, instead of waiting until the numbers get up here to cause trouble, once it goes from there to there, we intervene, change therapy to bring it back down.

Katherine:

Dr. Richter, why is it essential for patients to share any issues they may be having with their healthcare team?

Dr. Richter:

It is absolutely crucial because some things that may be very, very minor to them may be the tip of the iceberg of something very, very worrisome that we really need to investigate because sometimes, little problems are little now, and over time, they can become problems that we can’t so easily reverse. So, things like neuropathy, fatigue, or actually better yet, what I tell my patients is, “You know your body. If there is something out of the ordinary, big or small, let us know.”

And I would way rather a patient tell me 10 things in a row that mean nothing than not tell me about that one thing that means something.

So, for example, one of the disorders that’s associated with myeloma is called amyloidosis.

And when amyloid attacks the kidneys, you start to have protein in the urine, and this looks like bubbles, like foam in the urine. So, if someone has no foam when they urinate, and then over a period of months to years, they’re starting to notice lots of foam, tell me because that means we may need to look for things like amyloid. So, really any time something changes.

Katherine:

Anything. Yeah. I want to make sure that we get to some of the audience questions. So, let’s start with this one. PEN community member Sal sent in this question prior to the program. “What is the difference between myeloma and multiple myeloma?”

Dr. Richter:

A really great question. For the most part, the terms are synonymous. We abbreviate multiple myeloma as myeloma. But along those lines, and I literally saw a patient today who said, “Why is it called multiple myeloma?” Well, when you have a group of bad plasma cells that forms a tumor, we call that a plasmacytoma, “cytoma” meaning “bad cells,” and “plasma” because they’re plasma cells. And when you have one of them, it is a solitary plasmacytoma. Once you have two of them, it’s multiple myeloma because it’s in multiple spots in the marrow or multiple spots in the body. So, for our purposes, we use them interchangeably, but that’s where the “multiple” comes from.

Katherine:

Okay. Isaac sent us this question. How long does the average myeloma patient remain on Revlimid? And, is there a suggested time period?

Dr. Richter:

Really great question. It depends upon the setting we’re looking at, and for the most part, a lot of people are probably asking about the maintenance setting. So, after initial therapy or after transplant, we put you on Revlimid. How long do we keep you on? The American adage has always been, “More is better,” so as long as you tolerate it and as long as it works. Outside of the U.S., they’ve done a couple of studies looking at one year and then stopping, or two years and then stopping.

And in a big trial that got presented a year or so ago, they compared the two years then stopping versus just staying on, and the people who just stay on do better.

So, now the current thinking is just keep you on long-term. What’s going to change that in the long term is we’re starting to use a technology called MRD, minimal residual disease, so, doing a marrow and trying to find one in a million or one in 10 million cancer cells.

And then, there’s something called sustained MRD meaning if you do two MRD analyses at least 12 months apart and they’re both negative, we call that sustained MRD negative.

And, there’s a hint that some people on maintenance Revlimid who have sustained their MRD negativity, they may do just as well stopping versus staying on it. We don’t know exactly who that is yet, but that’s going to be better understood in the next few years.

Katherine:

Okay. Randall writes, “I was diagnosed last year with myeloma, and my first treatment worked, but now I’ve relapsed. Is it too late to consider a second opinion or a consult with a specialist? Would that change anything?

Dr. Richter:

It’s a phenomenal question. There have actually been studies to show that if you engage with a myeloma center at least once within your myeloma journey, you do better than someone who has never done that. So, it is never a bad time to seek out a specialist. And one of the good things that came out of COVID is telemedicine. So, if there’s not someone right in your area, reaching out to some of our advocacy groups to help connect you to physicians like me or any of my colleagues, we’re more than happy to see anyone, I’ll see you with an MGUS that’ll never bother you, as will all of my colleagues and people who work in myeloma.

If you’ve had one prior line, 15 prior lines, anywhere in between. So, I think it’s always a good idea to see a specialist because he or she is more than happy to work with your local doctor to optimize your treatment without having to necessarily go to another center.

Katherine:

Yeah. Well, thank you for all of that, Dr. Richter. And, please continue to send in your questions to question@powerfulpatients.org and we’ll work to get them answered on future programs. So, Dr. Richter, we’ve talked a lot about why patients should play a role in their care.

What advice do you have for patients to help them feel confident in speaking up and becoming a partner in their care?

Dr. Richter: So, that’s not always easy for a lot of people to do, and for some people, no problem. They’ll speak up at the first sign of anything. One bit of advice I would give to people who may have concerns or may not feel as comfortable about doing this is first of all, there’s a lot of members of the care team. So, I have patients that may not want to mention it to me, but mention it to my nurse or the medical assistant, and we all talk. So, that’s one way.

The other thing that I think may help is involvement in patient support groups, hearing what others have to say about similar experiences and learning from them, them learning from you, and that may actually give you more of a confidence to speak with your care team. But, the advocacy groups like the MMRF and IMF have tons of local support groups where you can sit in, and specialists come and speak or people share stories. And I think that can be really helpful to figuring out your optimal journey.

Katherine:

And knowing that you’re not alone –

Dr. Richter:

Absolutely.

Katherine:

– in how you’re feeling. As we close out this conversation, I wanted to get your take on the future of myeloma. What makes you hopeful?

Dr. Richter:

So, we’ve had what we call Gestalt switches in myeloma. And what I mean by that is let’s rewind decades ago. We gave chemotherapy. Chemotherapy was designed to kill any cell that divides rapidly because that’s what cancer cells like to do.

It kills the good and the bad. It makes your hair fall out, throw up, horrible stuff. It doesn’t work too well. Then about 20 years ago, we started this switch to the novel therapies, Revlimid, thalidomide, Velcade, and then a decade later, daratumumab. And now, we’re having targeted agents which spend more time targeting the bad stuff, less time doing off-target stuff, really ramping things up.

We are at the precipice of a brand-new Gestalt switch in myeloma.

The immune world. The immune therapies. And right now, T-cell redirection therapy is what we call it either with CAR Ts, where we take your T cells out, engineer them, and put them back into your body all revved up, or we give you an off-the-shelf, bispecific that grabs onto your cancer and your T cell and, brace yourself, we even have trispecifics, which can engage your myeloma, another cell in your body, and yet another cell.

If you go on clinicaltrials.gov, which lists all the trials for everything, every disease, there are over 3,000 active trials in myeloma.

And what I tell people is when I first started and I sat across from a patient, I would say, “I’m really sorry. It’s not curable.” And now I say, “We are curing some people today by accident.” But over the next period of time, we’re going to do this deliberately and more frequently. And the goal is and always has been 100 percent of cure for 100 percent of patients, 100 percent of the time.

And, I kind of feel right now we’re almost like that 2001: A Space Odyssey when the obelisk lands. We have these immune therapies. We know they’re great. How do we combine them? How do we use them? How do we take all these great tools and turn it into a cure for everyone?”

And with so many great partners between advocacy groups and Pharma and patients and cancer centers, we’re going to collaborate and we’re going to start getting those answers in my lifetime, and I could not be more excited about that.

Katherine:

Oh, I bet. I bet. It seems like there’s been so much progress and hope in the field. Dr. Richter, thank you so much for joining us today. It’s been a pleasure.

Dr. Richter:

Thank you so much for having me. I’d love to come back anytime.

Katherine:

And thank you to all of our partners. To learn more about myeloma and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us.

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.

See More from Thrive CLL

Related Resources:

 

Setting CLL Treatment Goals WITH Your Team

Signs It Is Time to Treat Your CLL

Signs It Is Time to Treat Your CLL

CLL Treatment Approaches: What Are the Types?

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.  

Thriving With CLL: What You Should Know About Care and Treatment

Thriving With CLL: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

What does it mean to thrive with chronic lymphocytic leukemia (CLL)? CLL expert Dr. Catherine Coombs discusses the goals of CLL care, reviews current treatment options, and shares tools for taking an active role in decisions.

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

Download Program Guide


Related Resources:

Thriving with CLL Resource Guide

What Are the Goals of CLL Treatment

What Are the Goals of CLL Treatment?

An Overview of CLL Treatment Types

Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re focusing on how to live and thrive with CLL. We’re going to discuss CLL treatment goals, and how you can plan an active role in your care.  

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Catherine Coombs. Dr. Coombs, welcome! Would you please introduce yourself? 

Dr. Coombs:

My name is Catherine Coombs. I am an assistant professor of medicine at the University of North Carolina. My main patient practice is CLL and SLL patients, which make up probably about 80 percent of the patients I see. I do see a couple other types of leukemia and precursor states as well.  

Katherine:

Thank you so much for taking the time out of your schedule to join us today; we appreciate it.  

Dr. Coombs:

No problem. My pleasure.  

Katherine:

Since this webinar is part of PEN’s Thrive series, I thought we could start with getting your opinion on what you think it means to thrive with CLL? 

Dr. Coombs:

I’d say the first thing that comes to mind when I hear thriving in CLL is my goal for all my patients, which is to live their lives and enjoy their lives, and to not let CLL take over their lives in any way. But it’s of course important to be knowledgeable and educated about how the disease can impact one’s life. But I think there is a lot of education that can also go with that to help individuals continue to enjoy their lives and do most of the activities they like within reason.  

Katherine:

This helps us guide us through the conversation, so thank you for that. Appropriate treatment obviously is part of thriving. Before we get into the specifics of CLL treatment approaches, how would you define treatment goals?  

Dr. Coombs:

The first thing to jump into prior to going into treatment goals is asking the question, “Is treatment even needed?” CLL, in contrast to pretty much most other cancers, is not one of the cancers that needs to be treated immediately.  

At least in 2022, there’s no proven benefit to early treatment. That is being questioned now that we have drugs that are much better tolerated. There are some nice clinical trials asking that question again, “Is early treatment beneficial?” At least what we know now is that is not the case. As it turns out, probably up to a third of patients with CLL never need treatment in their lifetime. That means that the disease progresses along usually at a slow pace, and individuals die from something else: any number of other potential causes of death.  

The other two-thirds plus do need treatment at some point in their lifetime. The goals of treatment kind of depend on the patient. There’s not a one-size-fits-all approach in my view. I think it depends on what is most important to the patient.  

I’ll give two drastic examples just to show how goals can be different. CLL often is a disease of older individuals. The average age of diagnosis is usually around 70 or so. But many patients have the disease for a few years, if not longer, prior to needing therapy. So, one example patient could be an 85-year-old individual who has had the disease for a decade and finally needs treatment. The goals of that patient may be to control disease, but he or she may not be worried about going into a deep remission, and may be very, totally willing to be on a drug. And definitely in order to control the disease, alleviate disease-related symptoms, but perhaps not get into a deep remission.  

The other patient, just to take it to another far extreme, I work in an academic medical center; I see some very young patients which is not the norm in CLL, but it does happen.  

Say it’s a 40-year-old patient. His or her goals may be very different. They may not like the idea of being on an oral therapy indefinitely or until progression. So, the goals for that patient may be different. They may say, “Gosh, I’d like to do something a bit more intense to be able to be off of therapy.”  

So, I think in the end there’s no one-size-fits-all approach. It generally, for my clinic, comes down to a discussion with the patient talking about what their goals are: is it more important to be off therapy for some period of time and they’re willing to sacrifice a bit more intensive of a schedule? Or are they more appealing to be on a regimen that they’re on indefinitely provided that it still provides disease control and alleviation of the disease-related symptoms.  

Katherine:

That leads me to my next question, which is what is the patient’s role in setting care goals? 

Dr. Coombs:

I think they should have a huge role; it should be a shared decision between the patient and their cancer doctor. I think at least as of now, there’s not one proven best therapy. We have a number of therapies that work extremely well. But they differ quite a bit with respect to the schedule, the possible side effects profile, and sometimes in the cost, depending upon the patient’s insurance. 

Knowing that there’s not a superior therapy, I think the best approach would be to discuss all of the therapies that are highly effective, and then compare and contrast what those therapies may look like for the patient and then make a shared decision.  

Katherine:

I have a follow-up question to what we were talking about a moment ago. 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.  

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 brutons 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. And then the newer agent is called acalabrutinib. There’s another drug that you may have heard of called zanubrutinib. 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 No. 1 they’re tolerating them, so no bad side effects, and then No. 2 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, 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. 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.  

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 1.) If the patient has low blood counts due to the CLL, so that could be anemia or low platelets. 2.) If they have bulky lymph nodes. They actually define bulky as 10 cm. 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. 3.) 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.  

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.   

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.  

Often times patients have both of these findings: a 17p deletion and a TP53 mutation. But sometimes you can have the mutation without the deletion and vise 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.  

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.  

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. 

Katherine:

As we close out this conversation, Dr. Coombs, I wanted to hear why you feel patients should be hopeful about the potential to thrive with CLL? 

Dr. Coombs:

There’s just so many reasons to be hopeful. CLL, I’d say more than – obviously it’s the cancer I’m focused on, but I think more than almost any other cancer has had advances that have really changed the lives of our patients in the last decade. And that’s only going to get better.  

We have therapies that work phenomenally well and can get you into remission, get the CLL under control, and let you just live your life as you wish; almost as though the CLL is not there. Though, it is in the background and your doctor can counsel you on special precautions needed. The drugs we have are phenomenal, but we only use them when we need them. Again, we don’t want to give you something you don’t need. But when you need it, the options we have are really phenomenal and they work well.  

They have some side effects, but I’d say they’re much better than the side effects of the older fashion drugs we used to use a decade-plus ago. The disease is there, we have better ways to control it, and I think there’s plenty of reasons to live your life, enjoy your life, thrive. We’ll take care of the CLL with all these tools in our toolbox when we need to.  

Katherine:

Dr. Coombs, thank you so much for joining us today.  

Dr. Coombs:

It’s been my pleasure, thank you.  

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