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Key CLL Treatment Decision-Making Factors

Key CLL Treatment Decision-Making Factors from Patient Empowerment Network on Vimeo

What should a patient consider when deciding on a chronic lymphocytic leukemia (CLL) treatment approach? Dr. Susan O’Brien, a Hematology-Oncology specialist, provides key factors that help guide treatment choices for patients with CLL.

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

See More From The Pro-Active CLL Patient Toolkit


Related Resources

 

Should You Discuss a CLL Clinical Trial with Your Doctor?

What Are Common CLL Treatment Side Effects?

What Should You Know About the Future of CLL Treatment?

Transcript:

Katherine:

Dr. O’Brien, once it’s determined that it’s time to move forward with treatment, what do you take into consideration to help guide the treatment choice?

Dr. Susan O’Brien:     

Well, the good news and the bad news are kind of the same. The bad news is it’s a very complicated decision, but the good news is the reason it’s complicated is because we have a lot of good options. So, as I said, there are some people for whom chemotherapy would still be an option. One of the benefits of that is that it’s intravenous, i.e. there’s no copays for the patient. It’s administered over a finite period of time. Generally, six months.

And then, most patients will get several years of remission after that where they don’t have to be on any treatment. However, we now have what we call the small molecules or the targeted therapies and those come in two major categories. One is called BTK inhibitors. And there we have two drugs available in the same family, if you will. One is ibrutinib. One is acalabrutinib.

And then we have a different category of oral treatment where we only have one drug, which is a BCL-2 Inhibitor, which is Venetoclax. So, what these drugs do, they’re not chemotherapy, but they interfere with certain proteins in the CLL cell. And by doing that, cause the cell to die off.

Katherine:                  

Okay. What do you feel is the patient’s role in this decision?

Dr.Susan O’Brien:      

Well, I think the patient plays a key role, which they usually do when there’s options because then you have – you with your doctor have to make a choice. So, for example, we talked about chemotherapy is time limited and you generally will be done after six months in contrast, with the BTK inhibitors, those are given indefinitely. They’re pills but given indefinitely for several years.

With Venetoclax it’s given with an antibody, which is given intravenously but the Venetoclax can be stopped after 12 months. So, the side effect profiles are different also. So, we have to take into consideration the duration of the therapy as well as the side effect profiles in determining what might be best for that patient.

How Do You Know If Your CLL Treatment Is Working?

How Do You Know If Your CLL Treatment is Working? from Patient Empowerment Network on Vimeo.

How do you know if a chronic lymphocytic leukemia (CLL) treatment approach is effective? Dr. Susan O’Brien, a Hematology-Oncology specialist, explains how CLL treatment response is monitored.

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

See More From The Pro-Active CLL Patient Toolkit


Related Resources

 

Should You Discuss a CLL Clinical Trial with Your Doctor?

What Are Common CLL Treatment Side Effects?  How to Be A Partner in Your CLL Care

Transcript:

Katherine:

But how is that treatment monitored to evaluate its effectiveness?

Dr. Susan O’Brien:

Well, generally the things we’re – the same things we’re look – the same things we’re looking at when we treat. Right? So, we’re looking at abnormal blood counts. We’re looking at enlarged lymph nodes or spleen. We have symptoms. So, those three things are looked at when the patient is on the therapy. Are the lymph nodes shrinking? Are the blood counts improving? Are their symptoms getting better?

So, the same way pretty much that we would follow a patient who’s not on a clinical trial is the way we follow them on a clinical trial. Now, if it’s a very new drug which has never been given to humans before, let’s say, those trials probably have more frequent surveillance than we might do with a drug that we are familiar with and know what to expect with it. So, sometimes the trials might have more surveillance, more visits, more tests.

But generally, if those tests or visits are required – are not considered standard of care, the companies pay for them. So, usually what’s billed to the insurance is only what we would do treating any CLL patient with an already available drug.

So, it doesn’t wind up costing the insurance or the patient any more to be on a clinical trial. And they might get actually – there is some data the patients on clinical trials get better care because they’re being monitored very carefully as part of the trial.

Should You Discuss a CLL Clinical Trial with Your Doctor?

Should You Discuss a CLL Clinical Trial with Your Doctor? from Patient Empowerment Network on Vimeo.

Dr. Susan O’Brien, a Hematology-Oncology specialist, explains why patients with chronic lymphocytic leukemia (CLL) should consider a clinical trial and the role trials play in treatment and care.

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

See More From The Pro-Active CLL Patient Toolkit


Related Resources

 

What Should You Know About the Future of CLL Treatment?

What Are Common CLL Treatment Side Effects?  How Do You Know If Your CLL Treatment is Working?

Transcript:

Katherine:

Dr. O’Brien, where do clinical trials fit in in all of this? Should patients discuss clinical trials with their physicians?

Dr. Susan O’Brien:

Absolutely. If we think of these great drugs that we have now, and I’ve mentioned ibrutinib, acalabrutinib, Venetoclax. Before those drugs were available, the only options were chemo. So, that means that people that went on the clinical trial, so let’s say with ibrutinib, have access to a really treatment changing revolutionary drug in CLL years before it was commercially available.

So, clinical trials can be a great way to have access to drugs or combinations. So, for example, right now there are some clinical trials looking at combinations of a BTK inhibitor and a BCL-2 inhibitor. So, the patient might say, “Well, why can’t you give me that combination, doctor?” “Well, technically I could.” If the drug is approved by the FDA, a physician can prescribe it really pretty much anywhere they see fit.

However, does insurance pay for it? That’s the trick. And these are very, very expensive drugs. And so, outside of an FDA approved combination, it probably wouldn’t – I wouldn’t be able to prescribe that combination because it wouldn’t get paid for and it would cost thousands and thousands of dollars. But on a clinical trial in general, the drugs are paid for.

Katherine:                  

Mm-hmm.

Dr. Susan O’Brien:     

And so, clinical trials are testing, for example, combinations now, which are not standard and there are some preliminary data from some of these trials that look really promising, i.e. two drugs may be better than one. There are also patients who, perhaps we’re talking about younger patients now, who have kind of worked their way through the available therapies. And so, they might not have a standard therapy that’s really gonna work for them. And for whatever reason they might not be a good candidate for stem cell transplant.

And so, innovative or totally novel drugs that we don’t have that class of drugs available at all are also being tested in clinical trials and allow people access to them. So, sometimes it’s – I think some people think of it as, well, a last resort if the drugs that are out there don’t work. But don’t think of it that way, because as I mentioned, these combination trials are for people who’ve never had prior therapy, but their disease has progressed enough to need treatment and could potentially offer, at least at a preliminary level, looks like a dynamite combination of drugs.

So, it’s not just for people who failed other drugs or whose disease has failed other drugs. That could be one group that is particularly important for, but even patients who’ve never had treatment, there may be clinical trials that they would be highly interested in participating. And again, it generally has a big financial benefit too, because remember oral drugs have copays for cancer patients.

Is It Time to Treat Your CLL? What You Need to Know

Is It Time to Treat Your CLL? What You Need to Know from Patient Empowerment Network on Vimeo.

When it’s time to move forward with a chronic lymphocytic leukemia (CLL) treatment plan, what determines the best therapy for YOU? In this webinar, Dr. Susan O’Brien, reviews key decision-making factors, current CLL treatments and emerging research.

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

Download Program Resource Guide

See More From The Pro-Active CLL Patient Toolkit


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How to Learn More About Your CLL

Transcript:

Katherine:                  

Hello and welcome to the webinar. I’m Katherine Banwell, your host for today’s program. Today we’ll discuss how you could work with your physician to find the best CLL treatment path for you. Joining me is Dr. Susan O’Brien. Welcome Dr. O’Brien. Would you please introduce yourself?

Dr. O’Brien:                

Sure. I’m Susan O’Brien. I’m the Associate Director for Clinical Sciences at the Chao Family Comprehensive Cancer Center in Orange, California.

Katherine:                  

Excellent. Thank you. And a note before we begin. This program is not a substitute for medical advice. Please refer to your healthcare team. Many CLL patients start in a period called watch and wait. Would you give us a brief overview of this approach?

Dr. O’Brien:                

Sure. The reason that we do watch and wait, or as some patients like to call it, watch and worry, is because many people present asymptomatically. So, for example, it’s very common that a patient might be found to have CLL because they go in for a routine physical and they have a slightly elevated lymphocyte count. So, many people have no symptoms at all. The average age of the disease is about 71.

So, people at the age of 71 often have what we call comorbidities. So, what does that mean? High blood pressure, high lipids, coronary artery disease. So, they also have a lot of comorbidities and even though right now we have great treatments for CLL that are generally well tolerated, all drugs do have side effects. So, if a person feels fine and the disease is not causing any problem in their life, why give them a treatment for it?

Particularly if we think that we don’t have a curative strategy. There may be a cure fraction for a small subset of patients with CLL who are young and have what we call a mutated immunoglobulin gene. But they’re a minority of most patients with CLL. So, what we want to do is keep people alive as long as we can with CLL until they likely die of other causes that people die of as they age. Heart disease, et cetera.

So, if they don’t need any treatment, we don’t want to expose them to the side effects. And some people, if you take all comers, everybody diagnosed with CLL, about a third of people will actually never need treatment for their disease. And so, that’s the idea behind it. That we’re sparing people side effects from treatments when they feel fine and their quality of life is perfectly good.

Katherine:                  

How do you decide when it’s time to treat?

Dr. O’Brien:                

So, it’s very variable because there are different indications from treatment in CLL. When I’m teaching my fellows, what I say to them is you basically treat the disease when it’s causing a problem. There are published guidelines, but they’re guidelines. They’re suggestions about when you might need to treat. But we take into account a number of different things. And in two different people the indications for treatment could be completely different. So, let me give you two examples.

 We could have a patient where they have big lymph nodes maybe in their neck, under their arms, in the groin, in the abdomen. And those nodes are getting bigger and bulkier to the point where they’re really problematic. That could be an indication for treatment. Other people might have very small lymph nodes but have very abnormal blood counts. So, their lymphocyte count could be really high. They could be starting to get anemic where their hemoglobin is dropping.

If you get too anemic, what’s going to happen? You’re gonna be symptomatic with fatigue and shortness of breath. So, we want to intervene not at a time when the disease is not causing any problems, but we also have to kind of find a happy medium. We don’t want to intervene – and wait until the patient is sort of bedridden and then start to do anything about the disease.

So, it’s a little bit of a judgement call. We also take into account the symptoms that the patient might be having. Like, are they having really terrible night sweats and fatigue that’s impacting their daily activities? So, we look at symptoms, we look at blood counts, and we look at lymph nodes or bulk of disease.

Katherine:                  

Where does genetic testing fit into the plan to treat?

Dr. O’Brien:                

There are certain tests that we definitely want to do before treatment. And some people have these tests done at diagnosis. So, the two main tests I would say are FISH, which just stands for fluorescence in situ hybridization, which is a fancy word for looking at chromosome abnormalities inside the CLL cell. The other thing we look at is the immunoglobulin mutation status. So, a patient’s immunoglobulin can be mutated or unmutated.

The immunoglobulin mutation status never changes. So, if a patient has had that test done once, they don’t have to have it repeated. However, the FISH, or the chromosome test, can change. So, it’s very important even if it was done at diagnosis that we repeat it at a time when a patient needs therapy. And why that’s so important is there is a particular chromosome abnormality called a 17p deletion where we know that those patients respond very poorly to chemotherapy.

And so, really should never receive chemotherapy and should receive a targeted therapy if that’s the case. There are other people that still could benefit potentially from chemotherapy, but not if they’re in that 17p deletion group.

Katherine:                  

All right. Dr. O’Brien, once it’s determined that it’s time to move forward with treatment, what do you take into consideration to help guide the treatment choice?

Dr. O’Brien:                

Well, the good news and the bad news are kind of the same. The bad news is it’s a very complicated decision, but the good news is the reason it’s complicated is because we have a lot of good options. So, as I said, there are some people for whom chemotherapy would still be an option. One of the benefits of that is that it’s intravenous, i.e. there’s no copays for the patient. It’s administered over a finite period of time. Generally, six months.

And then, most patients will get several years of remission after that where they don’t have to be on any treatment. However, we now have what we call the small molecules or the targeted therapies and those come in two major categories. One is called BTK inhibitors. And there we have two drugs available in the same family, if you will. One is ibrutinib. One is acalabrutinib

And then we have a different category of oral treatment where we only have one drug, which is a BCL-2 Inhibitor, which is Venetoclax. So, what these drugs do, they’re not chemotherapy, but they interfere with certain proteins in the CLL cell. And by doing that, cause the cell to die off.

Katherine:                  

Okay. What do you feel is the patient’s role in this decision?

Dr. O’Brien:                

Well, I think the patient plays a key role, which they usually do when there’s options because then you have – you with your doctor have to make a choice. So, for example, we talked about chemotherapy is time limited and you generally will be done after six months in contrast, with the BTK inhibitors, those are given indefinitely. They’re pills but given indefinitely for several years.

With Venetoclax it’s given with an antibody, which is given intravenously but the Venetoclax can be stopped after 12 months. So, the side effect profiles are different also. So, we have to take into consideration the duration of the therapy as well as the side effect profiles in determining what might be best for that patient.

Katherine:                  

Well, you talked about chemo and targeted therapies, but where – where’s stem cell treatment fit? Where does – where does stem cell treatment fit in and when is it considered?

Dr. O’Brien:                

So, stem cell treatment – if we’re talking about stem cell transplant, allergenic stem cell transplant is a transplant where you need a donor and you receive stem cells from the donor. And that can be a curative therapy, but it can also be associated with significant risks including risk of dying from the transplant. Because we have so many effective therapies nowadays, we’re generally not needing to use allogenic transplant.

And what I mean by that is if these targeted therapies don’t cure people, and the jury is still out on that I would say, if we can sequence them such that we get five years from one, six years from another, et cetera, we’re going to be able to keep the patient alive long enough until they die of something else. So, where the stem cell transplant comes in is generally much younger patients with CLL.

I mentioned the average age is 71, but we have – all of us int eh field have seen patients, for example, in their 30’s. Well, yes, a sequence of therapies might not get that patient to a normal lifespan, because they’re so young to start. So, really the consideration is pretty much reserved for younger patients where we might need a curative strategy that we might not have otherwise.

But for older patients, we probably have enough active drugs now. We have other categories of drugs that we can use if the disease reoccurs. So, we have enough categories of drugs that I think we can keep most people who are the average at CLL alive for quite a long time.

Katherine:                  

What about CAR-T therapy? Where do we stand on that with that research?

Dr. O’Brien:                

So, my answer is a little bit like allogenic stem cell transplant. CAR-T therapy is also associated with significant risks, but also significant benefit. Up until now, it’s pretty much been reserved because of the risks for patients who, to be frank, their disease has now kind of escaped everything. We don’t feel like we have great options that are similar and easier to use.

So, it can be effective, but it’s not something we do very early on because of the associated risks. If you take patients who go for CAR-T therapy, about 25 to 40% of them will wind up with some stay in the ICU. So, I’m really talking about some serious complications from these therapies.

It’s possible that as we learn how to minimize the toxicities of CAR-Ts, that they might become a more attractive strategy. And so, that could change with time. But the counterpoint to that is we’re having new drugs approved all the time for CLL. So, that gives us also more options before we would need to move to a CAR-T.

Katherine:

Dr. O’Brien, where do clinical trials fit in in all of this? Should patients discuss clinical trials with their physicians?

Dr. O’Brien:                

Absolutely. If we think of these great drugs that we have now, and I’ve mentioned ibrutinib, acalabrutinib, Venetoclax. Before those drugs were available, the only options were chemo. So, that means that people that went on the clinical trial, so let’s say with ibrutinib, have access to a really treatment changing revolutionary drug in CLL years before it was commercially available.

So, clinical trials can be a great way to have access to drugs or combinations. So, for example, right now there are some clinical trials looking at combinations of a BTK inhibitor and a BCL-2 inhibitor. So, the patient might say, “Well, why can’t you give me that combination, doctor?” “Well, technically I could.” If the drug is approved by the FDA, a physician can prescribe it really pretty much anywhere they see fit.

However, does insurance pay for it? That’s the trick. And these are very, very expensive drugs. And so, outside of an FDA approved combination, it probably wouldn’t – I wouldn’t be able to prescribe that combination because it wouldn’t get paid for and it would cost thousands and thousands of dollars. But on a clinical trial in general, the drugs are paid for.

Katherine:                  

Mm-hmm.

Dr. O’Brien:                

And so, clinical trials are testing, for example, combinations now, which are not standard and there are some preliminary data from some of these trials that look really promising, i.e. two drugs may be better than one. There are also patients who, perhaps we’re talking about younger patients now, who have kind of worked their way through the available therapies. And so, they might not have a standard therapy that’s really gonna work for them. And for whatever reason they might not be a good candidate for stem cell transplant.

And so, innovative or totally novel drugs that we don’t have that class of drugs available at all are also being tested in clinical trials and allow people access to them. So, sometimes it’s – I think some people think of it as, well, a last resort if the drugs that are out there don’t work. But don’t think of it that way, because as I mentioned, these combination trials are for people who’ve never had prior therapy, but their disease has progressed enough to need treatment and could potentially offer, at least at a preliminary level, looks like a dynamite combination of drugs.

So, it’s not just for people who failed other drugs or whose disease has failed other drugs. That could be one group that is particularly important for, but even patients who’ve never had treatment, there may be clinical trials that they would be highly interested in participating. And again, it generally has a big financial benefit too, because remember oral drugs have copays for cancer patients.

Katherine:                  

Right. But how is that treatment monitored to evaluate its effectiveness?

Dr. O’Brien:                

Well, generally the things we’re – the same things we’re look – the same things we’re looking at when we treat. Right? So, we’re looking at abnormal blood counts. We’re looking at enlarged lymph nodes or spleen. We have symptoms. So, those three things are looked at when the patient is on the therapy. Are the lymph nodes shrinking? Are the blood counts improving? Are their symptoms getting better?

So, the same way pretty much that we would follow a patient who’s not on a clinical trial is the way we follow them on a clinical trial. Now, if it’s a very new drug which has never been given to humans before, let’s say, those trials probably have more frequent surveillance than we might do with a drug that we are familiar with and know what to expect with it. So, sometimes the trials might have more surveillance, more visits, more tests.

But generally, if those tests or visits are required – are not considered standard of care, the companies pay for them. So, usually what’s billed to the insurance is only what we would do treating any CLL patient with an already available drug.

So, it doesn’t wind up costing the insurance or the patient any more to be on a clinical trial. And they might get actually – there is some data the patients on clinical trials get better care because they’re being monitored very carefully as part of the trial.

Katherine:                  

Let’s turn to patient self-advocacy. How can patients feel confident in speaking up and becoming a partner in their own care?

Dr. O’Brien:                

Yes, obviously for some people that’s going to be a lot harder than others. What I generally advice people is if you’re going in for your physician and you’re diagnosed with CLL, I would say this for any cancer because cancer is obviously a potentially life changing diagnosis, is you probably want to get an opinion with an expert. I would talk to my doctor first, ask them what their plan is so I know, and then see an expert in the field.

Then if the expert in the field says, “I think your doctor’s plan is great.” 1.) you’re now comfortable because you’ve got a second opinion, and 2.) that’s also a way, in my experience, to know if your doctor’s really gonna allow you to have an easy time participating. What I mean by that is that if your doctor is upset or finds it offensive, quite frankly you probably need a new doctor. That’s my take on that. Because that means they’re not going to be too open to your comments or you’re saying, “Well, I would prefer to do this.”

That’s just my quick take on how you can tell if it’s going to be easy or hard. But I think the relationship between the doctor and the patient is very important and you have to establish that relationship early on. If you go to a doctor who – where you start to ask questions and they’re in a hurry or they’re looking at their watch, you know that’s probably not the doctor that you want. I think most doctors realize that if they’re diagnosing a patient with a cancer, that’s going to be a pretty long clinic visit, because any patient is going to have a lot of questions to ask.

I also tell patients when you go to see a specialist or get a second opinion, bring somebody with you. It’s very well known that when patients have just been diagnosed with a cancer, they’re overwhelmed. Their emotional system is overwhelmed. Even if it’s “not a bad cancer”. Maybe early stage CLL. And that makes it very hard to process what a doctor is saying.

Particularly if they’re trying to give you quite a bit of information, which you need because you’ve just been diagnosed, and you need to know what to expect from the disease. So, having a friend or a spouse or a significant other there is really, really helpful.

Katherine:                  

Yeah. Yeah. That’s really good advice. Are there resources to help patients stay informed and educated?

Dr. O’Brien:             

Oh, yes. Our Leukemia and Lymphoma Society is great at that. Lymphoma Research Foundation were two of the big ones. And then there’s patient spots. CLL Society is a very well-known one run by a physician who’s also a CLL patient. I know him very well. And they have online support meetings now.

They used to have them in person, but now they have them online. And those can be really helpful because that allows a patient to talk to another patient who has their same disease. So, there are quite a lot of resources for patients nowadays. Especially in our technology enabled world.

Katherine:                  

That’s great. We have a couple of questions from patients. Patrick asks, “I’ve discussed a treatment plan with my doctor, but I’d like to get a second opinion. What are your thoughts on that?”

Dr. O’Brien:             

I think it’s a great idea. That’s exactly what I would do if I had a cancer. And again, I think Patrick made an important point that I’d like to emphasize. See what your doctor’s plan is first. Because then when you go to see the specialist or the second opinion, you can say, “This is what my doctor’s suggesting.”

And then if the specialist says, “Exactly what I would do.” But if you don’t know what your doctor is going to do – was suggesting to do when you go in to see the second opinion, it’s going to be really hard to make sure –put together that feeling of confidence that you’re on the right track.

Katherine:                  

Right. Right. To judge. A question from Julie. “How do you approach treating a relapse?”

Dr. O’Brien:

So, treating relapse we do the same thing that we do upfront. Namely “watch and wait”. So, for example, if a patient had a treatment on – let’s say they had some chemotherapy. And three or four years alter the lymphocyte count starts to go up, well, that technically would be indicating relapse.

But let’s say for the sake of discussion the person is asymptomatic, they feel fine, and their lymphocyte count is 20,000. Well, why do we need to do anything? So, in most cases we take the same approach of watch and wait when the disease comes back. And the first point at which it comes back is not always the time at which we need to initiate therapy.

Katherine:                  

Right. Right. Another question. Will is wondering, “If inhibitor treatments have to be taken forever?”

Dr. O’Brien:                

Well, it depend on the group – the class. So, for the BTK inhibitors, all the trials so far have given those drugs indefinitely. For the BCL-2 inhibitor, Venetoclax, there are time limited regimens both in the frontline setting and in relapse. But realistically, I have talked to my patients who are going on a BTK inhibitor who say to me, “Do I really have to be on this forever?”

And so, my answer is, “I don’t know what life is forever, so I would never use that word. We generally use the word indefinite.” But what I’ve said to those patients is, “If you’re on the drug for a while – and I’m not talking months. I’m talking say two, three years. And you’re in a really good remission and you think you want to stop treatment. I’m not necessarily opposed to that.”

Because if you’re in a very good remission, even if it’s not complete, but most people who are not in complete remission, meaning they still have a bit of disease left, have very little disease if they’ve been on the BTK inhibitors for a while. So, maybe only some enlarged lymph node on a CAT scan or a little bit of disease in the bone marrow.

But basically, most people after a couple years, they’re blood counts are normal, they feel fine, unless they’re having side effects from the drug and their physical exam is normal. So, I’ve told my patients if you want to go off, I expect you’d probably be off for even a couple years. And then we could always restart therapy potentially with that drug again or with one of the other drugs.

So, I think it’s important to let people know that they have options. But I will say that all of the clinical trials with the BTK inhibitors have given those drugs basically until the patient loses their response or there’s a toxicity where they just don’t want to take the drug anymore.

Katherine:                  

Mm-hmm. Mm-hmm. One last question from Jen. “What should be considered related to side effects when choosing a treatment plan?”

Dr. O’Brien:                

Well, the BTK inhibitors have some side effects. They can cause diarrhea, but that’s usually mild and self-limited. They can sometimes cause joint aches or arthrology. They – the two probably most serious side effects are atrial fibrillations, which is an irregular heart rate. But that generally is not frequent and tends to occur mainly in older men with heart disease.

Katherine:                  

Hmm.

Dr. O’Brien:                

They also are more likely – they impact the platelet function. So, they can more likely cause bleeding, but it’s typically minor bleeding like a bruise. Major bleeding is quite rare. In general, I’m outlining a lot of side effects, but remember not all side effects occur in everybody and there’s some people who don’t have any.

For the BCL-2 inhibitor, Venetoclax, one of the things we have to be very careful of when a person first goes on that and this would be particularly true if they have a very high lymphocyte count or a bulky lymph nodes, it that drug can cause something called tumor lysis. Tumor lysis, lysis is just a fancy word for breakdown, is where the disease responds so rapidly that their lymph nodes shrink very quickly. Lymphocyte comes down, which sound really good.

But what can happen is that breakdown of the cells can release potassium which can cause heart arrythmias. The cells can clog the kidneys and cause kidney failure. So, we have to be very careful about that when we start. And the way that drug is started is it comes with a starter pack actually to help make it easy where you go up, you start at a low dose, and go up weekly until we get to the target dose.

But we have to monitor very carefully during that escalation phase. The other thing that the Venetoclax can cause is neutropenia, meaning low neutrophil counts. What – that’s important because neutrophils are what we use to fight infection. So, if we get low neutrophil counts, the options are either to add a growth factor transiently, in other words a shot to – the subcutaneous injection that stimulates the bone marrow to release neutrophils. Or if it’s really a persistent problem, then we can go down on the dose of Venetoclax.

Katherine:                  

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

Dr. O’Brien:                

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

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

Katherine:                  

Are there emerging treatments that patients should know about?

Dr. O’Brien:                

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

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

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

Katherine:

Hmm. One last question, Dr. O’Brien. In this uncertain time, do you have any advice related to COVID-19 for CLL patients?

Dr. O’Brien:                

It’s a hard time for everybody and particularly CLL patients because we know that they’re immunocompromised by – and even if you’ve never been treated and you probably never get any infections, which is quite a number of people with CLL, unfortunately you do have to think about yourself as being a high-risk patient.

So, masks are very important. Washing hands. Avoid – social distancing. Avoiding crows. It’s really important for patients with CLL to follow those same guidelines that we’re giving to everybody. But very important for them because they are in a higher risk group.

Katherine:

How do you feel telemedicine is working for CLL patients?

Dr. O’Brien:                

Telemedicine works I’d say better for CLL patients than some other patients, particularly watch and wait patients. Obviously the one thing that we can’t do in telemedicine is a physical exam. But in patient we can get – have patients get their blood counts done and then talk to them and see how symptomatic they are and know what their blood counts indicate anything is changing.

And then what I’ve been doing is, say I have a watch and wait patient – or it also applies let’s say to a patient who’s been on ibrutinib for years now and they’re in remission. There’s probably nothing to exam anyway. Right? So, those patients are good. I think it’s not going to work very well if you’re starting a new treatment. But for people who are watch and wait or have been on established treatments that are doing well, it works really well.

And then you can use the video visit if the patient says, “This is going on.” Whatever it is. “And I think I’m worried about this or I have this pain here.” Or whatever. If that’s an issue, you can always then schedule a regular visit. Right?

But I think that it – because it’s a chronic disease as opposed to acute leukemia where you really can’t do video visits, I think it lends itself to it very well. And my expectation is that moving forward, even after hopefully COVID has died down or we have a vaccine, that video visits are definitely here to stay.

Katherine:                  

Yeah. Yeah. I agree with you. What about patients who are fearful going into a medical center? Do you have any advice for them?

Dr. O’Brien:                

Usually – and it does vary. I also would be nervous if it was a hospital-based place where I had to go for my visit. But for example, where we are in the cancer center, it’s a completely separate building. Everybody is temperature checked before they get in. Everybody has to fill out a questionnaire about their symptoms. If they do have a low-grade temperature, we immediately triage them to another area.

So, actually I think the cancer center is probably a pretty safe place to be. Probably safer than the grocery store in that sense, because of the screening and the testing of the temperature of everybody who comes in there. And, of course, everybody has a mask on.

So, I would be probably a little bit weary in a hospital setting where they may be many sick patients hospitalized with COVID. But I think in a lot of clinic buildings or freestanding buildings, I probably would not be that worried.  

Katherine:                  

Well, Dr. Susan O’Brien, thank you so much for joining us today. 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. Thank you so much for joining us.

How Does COVID Impact CLL Patients?

How Does COVID Impact CLL Patients? from Patient Empowerment Network on Vimeo

How has chronic lymphocytic leukemia (CLL) care been impacted in the age of COVID-19? Dr. Phillip Thompson explains how COVID affects CLL patients and the importance of not delaying CLL treatment.
 
Dr. Phillip Thompson is an Assistant Professor in Medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about this expert here.

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Transcript:

Dr. Philip Thompson:

There was a large ISH study published, I think, in Lancet Oncology, recently,  from the UK, where they looked at outcomes for patients with cancer. And of course, it was all patients with cancer, not specifically CLL, specifically blood cancers. But I think there were roughly 200 patients with hematologic malignancies.

And the interesting thing that I noticed, there were that patients who had recent chemotherapy, which I might have expected to be a really high-risk feature for a poor outcome, actually didn’t do any worse than patients who hadn’t recently been treated.

By far, the most important predictors of outcome for patients were whether their cancer was controlled or not, number one. And then other co-morbidities that patients had, like lung disease, advanced age, that sort of thing. So, actually, we need to see more data from more – from datasets that have more patients with CLL. But it seemed like the type of treatment mattered less than whether the disease was controlled and what other problems the patient had in terms of predicting their outcome from COVID.

So, I am taking that information with a – we have to, as I said, see more data. But I’m not going to use COVID as a reason not to patients who need treatment.

We may stretch things out somewhat in people where the decision is really well, and maybe you don’t definitely need to treat. But I don’t want to see people get into really severe trouble from their CLL because we’re trying to delay treatment because of COVID. Because that might actually be counterproductive. Because people with very uncontrolled CLL, if they were to get the infection, may actually have inferior outcomes to people whose disease is controlled.

Partnering With Your Doctor on CLL Treatment Decisions

Partnering With Your Doctor on CLL Treatment Decisions from Patient Empowerment Network on Vimeo.

Which CLL treatment could be right for you? Dr. Steven Coutre, a CLL specialist, reviews current approaches and explains why patients should stay informed about emerging options.

Dr. Steven Coutre is a Professor of Medicine in the Hematology Department at Stanford University Medical Center. Learn more about this expert.

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Transcript:

Dr. Steven Coutre:

Well, any decision about treatment is, of course, a joint decision between the physician and the patient. It’s our job to really educate each individual patient about their options and also, I think, very importantly, determine what their goals are. You don’t really follow a strict algorithm. It’s really making a decision for each individual patient.

So, of course that takes into account other medical conditions they may have, the nature of their disease, why it is that we’re treating that individual, what we’re trying to accomplish, and very importantly, what the goals of therapy are for that individual. That may be very different, for example, for somebody who’s quite young versus somebody who’s older or who might have significant medical comorbidities.

I think patients are always well served by asking questions about the treatment, side effects of treatment, of course, these days, cost comes into play, so I think we have an obligation to let patients know the differences between the therapies because often we have choices about a therapy. There isn’t any one best therapy, for example. It’s often a number of choices, and sometimes that can be very, in some ways, confusing for patients, because they wanna know, “Well, what’s the best therapy?” and as I mentioned, it’s not so much what’s the best. It’s what’s the best for that patient, and many times that’s choices of treatment.

Some are time limited, for example. Some are continuous therapies. So, there’s plusses and minuses, and again, it all goes back to what’s your goal for that individual patient, what are their preferences in terms of the treatment that they want to receive.

The drugs that I mentioned earlier are Bruton Acalabrutinib, Venetoclax, for example. These are really the first of our new really transformative drugs for CLL. Drugs, along sometimes, with our antibodies, Rituximab and Obinutuzumab, which are really replacing the use of chemotherapy in treating the disease. So, moving forward, we’re looking at combinations of these drugs. Can we drive responses deeper? That would lend itself to stopping therapy, in some case, instead of using continuous daily therapy as we currently do with drugs like Ibrutinib or Acalabrutinib.

So, that’s the major focus right now. There, of course, will be other new drugs. There’s a third drug, Zanubrutinib, which is another BTK inhibitor, so that’ll probably play a role in treating CLL. There may be differences in side effect profiles between these drugs. There isn’t any new drug that we’re looking at currently that’s far enough along to say that it’s gonna be yet another fundamentally different, revolutionary therapy for CLL. But those, of course, can come along as we learn more about the biology of the disease.

You may have heard about CAR T-Cell Therapy, where you’re using your body’s own immune system to try to target the cancer. This has been very successful and is actually approved for use in other diseases, like large cell lymphoma, for example, but it remains very much investigational in CLL. There are also other clever ways of trying to achieve the same, endpoint, that is, using your own immune system to target the cells, that are simpler than CAR T-Cell Therapy and those kinds of approaches are also in clinical trials.

So, when you’re having the discussion about treatment, it’s always good to learn about what the latest therapies may be, even if they are investigational. I think that’s how we move the field forward and, of course, the newer drugs that we have brought forward came from clinical trials that patients greatly benefitted from. So, always ask your physician about clinical trials. Another great source for that, I think, is the Leukemia Lymphoma Society. They’re very patient-focused, they’re very up to date on the latest therapies and the latest trial results. They have a very robust presence, both online, and also, generally locally. There’s local chapters. So, I would encourage you to reach out to them for information.

CLL & COVID 19: What Do Patients Need to Know?

CLL & COVID 19: What Do Patients Need to Know? from Patient Empowerment Network on Vimeo

What do people with chronic lymphocytic leukemia (CLL) need to know about COVID-19 (coronavirus)? CLL expert Dr. Steven Coutre provides guidance for patients during the current global pandemic.
 
Dr. Steven Coutre is a Professor of Medicine in the Hematology Department at Stanford University Medical Center. Learn more about this expert.

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Transcript:

Dr. Steven Coutre:

Well, of course, we are in the COVID era. We don’t know how long this is going to last. And so, a very common questions that comes up from our patients with CLL is what impact does this have on them and are they more susceptible, you know, the natural things that people wanna know. With CLL in general, there probably is some compromise to the immune system, but it’s really hard to measure or quantify. Certainly, individuals who’ve had a lot of chemotherapy in the past, who have advanced disease are more susceptible to infections. In contrast, someone who’s without symptoms, has a low burden of disease probably is close to being like somebody who doesn’t have CLL. So, there’s certainly a spectrum.

Really, we just try to advise following the guidelines that we are all following in terms of social distancing at present, at being aware of being around others too closely, or those who may have symptoms. So, I think, in a way, what everyone is doing now is something that is beneficial to patients with CLL, and certainly other cancers, with respect to infection risk.

Now, what about do we have any information? Is somebody with CLL more susceptible to getting COVID? What if you do get the infection? Is it going to be more severe because you have underlying CLL? And, at least in general terms, the answer seems to be no. That’s really just based on experience, anecdotal experience, certainly in areas like New York City or Italy, for example, where infectious rates have been quite high. Colleagues have commented that their patients don’t seem to be more ill simply because they have the underlying disease or because they’re on a certain treatment, for example.

There’s actually some very interesting data suggesting that perhaps the BTK inhibitors, Ibrutinib, Acalabrutinib, et cetera, might actually confer benefit, might lessen some of the consequences of the infection, and as a result, large clinical trials have started for patients without CLL. Just anyone who has a significant COVID infection who’s hospitalized, they’re testing that hypothesis. So, it’ll be very interesting to see what we learn from this. Perhaps what we’ll learn is that being on a drug like that might actually be beneficial.

It’s certainly natural to be hesitant to come into a healthcare facility because of the risk of infection, and certainly that’s gonna vary quite a bit depending on where you are. At the height of the pandemic in New York City, of course, a lot of concern on the part of patients going into a hospital clinic, for example. Whereas, at our institution, the impact has been quite low. All institutions, of course, have taken any precautions they can to limit exposure, so, I’ve often told my patients that it’s probably safer to come into our clinic and get your blood drawn or see someone if you need to than going to the grocery store, for example, in terms of exposure.

But that’s very different than saying the same thing in the middle of New York City. So, I think you have to deal with each situation as it arises, and one would hope that your physician can give you guidance. And I think, in particular, what we can do is really decide how important it is to see somebody in person or have them come in and get a lab test there. I think in many, many, many cases, that can be avoided for the time being.

And that also is an important point, that we can provide reassurance that you know, you’re used to coming in every four months or every six months and having things checked, and in many cases we can reassure that individual that it’s okay to wait. It’s not critical to get that information right now.

So, remember that what we often emphasize in evaluating someone and making decisions when to treat is three things. It’s how you feel, what your exam is like, and what your blood counts look like. So, of course, you know how you feel. If something changed, you’re having night sweats, or a lot more fatigue, is it significantly different? Of course, you typically know if anything’s changing with your exam. Are your lymph nodes getting enlarged?

Do you notice discomfort in your abdomen because of an enlarging spleen?

And so, two of the three things you can sort of self-assess, in a way, and then based on what your blood counts have been showing over time, your physician can factor that in and decide how important it is to get that test now. And as I mentioned, in many, many cases, it’s perfectly fine to delay that. So, it’s not as difficult as it might seem to you to be able to come up with a reasonable assessment about how somebody might be doing, even in the absence of seeing them and doing an exam in person.

How Can CLL Patients Take Advantage of Telemedicine?

How Can CLL Patients Take Advantage of Telemedicine? from Patient Empowerment Network on Vimeo.

In light of the global pandemic, many providers expanded their telemedicine options so that patients can connect with their physicians virtually and avoid in-person visits. Expert Dr. Steven Coutre explains how this approach could benefit people with chronic lymphocytic leukemia (CLL).

Dr. Steven Coutre is a Professor of Medicine in the Hematology Department at Stanford University Medical Center. Learn more about this expert.

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Transcript:

Dr. Steven Coutre:

Well, we are in a new era, at least temporarily, and, for example, we’ve switched almost exclusively to video visits. This had largely been used for patients who lived in remote areas. They didn’t have good access or ready access to healthcare providers, and so, the government reimbursed for those kinds of visits, but not for somebody who lived close by, for example.

Well, that all changed dramatically with the COVID infections, even for our patients on clinical trials. And we’ve done the grand experiment that never would have been done otherwise, of just suddenly doing all video visits, and I must say, it’s worked out quite well so far. I think patients are quite satisfied with it, by and large. It allows them to have their questions answered and continue to have appropriate monitoring if they’re on therapy, or even if they aren’t. And so, I think, when things improve, this will continue, to some extent. So, right now, I would expect that any CLL patient would have ready access to their hematologist or oncologist via video visit.

And also, I think this whole situation has promoted a lot more video conferencing, educational video conferencing. Not having to physically attend a conference in order to get information. So, I think they’ll see a lot more educational resources out there online for them.

Well, of course, with CLL, we’re also very interested in blood counts, as are our patients, and if we’re doing remote visits, or even if they live fairly close but aren’t coming in, we do try to get the lab work done, but that’s worked out quite well. We’re used to dealing with patients coming from far distances, and so, in the past, if we wanted to get a lab result in between visits, we would simply make those arrangements with their local lab. Everybody tends to have an internist, a family doctor that they see, and so they’re familiar with getting lab tests done near where they live, and in all cases, we’ve been able to accommodate that.

And now with the increasing of electronic medical record usage and interlinking of medical record systems, we can, for example, get lab tests done at a local lab and have those. Actually, those results are directly imported into the medical record. So, they’re easily accessible to us. So, I must say, it’s been a pleasant surprise to see how well this has worked.

Diagnosed with CLL? An Expert Outlines Key Steps

Diagnosed with CLL? An Expert Outlines Key Steps from Patient Empowerment Network on Vimeo.

You’ve been diagnosed with chronic lymphocytic leukemia (CLL), now what? Dr. Matthew Davids explains key steps to take following a diagnosis. Need help speaking up? Download the Office Visit Planner and bring it to your next appointment here.

Dr. Matthew Davids is the Associate Director of the CLL Center at Dana-Farber Cancer Institute. More about this expert.

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Transcript:

Dr. Matthew Davids

So, if I were diagnosed with CLL today, we’ve discussed some of the resources that are available in terms of educating one’s self about the disease: CLL Society website, other videos on VJHemOnc, things like this. There are other websites that give more basic information about the disease, for example, Lymphoma Research Foundation, American Cancer Society, American Society of Clinical Oncology.

So, personally, I would want to know a lot about the disease. And I would probably first turn to these particular resources, which I think can be very helpful.

I would certainly partner with a local oncologist hematologist who can help guide the management. But one thing that you should remember is that most general practitioners for oncology may only see a few CLL patients a year, and the field has changed quite a bit over the last few years. And it can be hard to stay completely up to date on all of these developments.

So, one thing that I would think would be very helpful for anyone diagnosed with CLL is that, if you do have access to a major center that has someone who specializes in CLL or at least in lymphomas, that can be a great resource. And so, I do recommend, if patients can do it, to try to seek out a second opinion from a CLL specialist. And this can be very helpful even if the recommendation is still just observation, that they can help educate about the disease, identify other resources for educational purposes, and just become a part of your team, to have them available down the line.

And I see many patients like this who come for a second opinion at diagnosis. And I kind of tell them, “Go back to your local doctor. Stay on observation. It’s likely you’ll do well for many years on this watch and wait strategy. But at the time when they’re recommending that you need treatment, come back and see me then. It’s easier to get in once I know you.”

And at that point, I can help reassess, 1.) Do I agree that treatment is really needed at that point? Sometimes, it’s actually possible to wait even a bit longer; and then, 2.) What would I recommend for the best treatment option at that time? Could be a clinical trial that might only be available at that center. And I think unless you have a CLL specialist on your team, it’s gonna be hard to know about those available resources.

So, it’s not that you necessarily need to follow exclusively with a CLL specialist. But it’s more to just have them involved, have them know about you. And that way, if you need them down the line, they’ll be available to help support you.

I think in terms of education and self-advocacy, this is a very personal issue. And so, for many of my patients, it’s very important that they are educated about the disease and kind of know the ins and outs of the different clinical trials and so forth.

But it’s also important to remember that that’s not gonna be true for every patient. A lot of my CLL patients are also older patients, and they may not want to know all the details of what’s going on. I think it is important to have someone who’s involved with your care know about these details. Ideally, if it’s not you, it might be a spouse or a partner or a child, for example. A lot of my older patients don’t wanna know all the details about the molecular biology and the clinical trials. But often, it’s their son or daughter who is there with them who wants to know this.

And so, I think it’s helpful often to bring a family member with you to the visits. Because as you can see even from today, there’s a lot of information to learn, and it can be hard to remember everything.

So, having someone else, another set of ears and eyes, someone else can maybe take some notes at the visit and review them with you later, I think can be very, very helpful in terms of your own self-awareness about the disease.

So, in general, I love when patients ask me questions. Sometimes, they are very savvy questions. They are familiar with the literature, and they can kind of really push me to explain my opinions and beliefs about certain treatments. And sometimes, they’re just very basic questions that may be seem silly to the patient but are really not silly questions.

Really, this is a brand-new area for most patients. They have no experience with this when they first start out. So, they should never feel like they’re bothering their oncologist with these questions. I think it’s really important for them to understand the basics of what’s going on. That should really be a minimum for every patient.

And then for patients who wanna know more about some of the details from the research and the clinical trials, I think their doctor should also be able to help explain that to them as well. So, they should never feel like they’re bothering their oncologist with their questions.

Could a Clinical Trial Be Your Best Treatment Option?

 

Could a Clinical Trial Be Your Best Treatment Option? from Patient Empowerment Network on Vimeo.

Is participating in a clinical trial a last resort or could it be your best treatment option? Dr. Matthew Davids explains the clinical trial process and what’s involved in patient participation.

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Transcript:

Dr. Matthew Davids

My patients often ask me about clinical trials and whether I think that would be a good fit for them. I think there is, in some cases, a bit of a misconception that clinical trials are a last resort for our patients. And we do have some clinical trials that are exploring brand new mechanisms of a drug that have never been used before.

And in that scenario, I would only recommend a trial like that for a patient who has already exhausted all of the standard options.

But I think that, in my opinion, clinical trials should really be the first best choice for most patients. Because we have many trials in CLL that are using the drugs that are already approved, so we know that they’re gonna be effective. And now, we’re putting them together for the first time in new combinations and in new creative ways that will help to advance the field. And most of the trials we have in CLL are not randomized, placebo-controlled. So, patients know what they’re getting. They’re gonna be getting an effective therapy.

And this is a way that they can really get access to cutting-edge care. I would say when you’re a part of a clinical trial, you have a lot of other eyes watching you. In addition to your oncologist and the infusion nurses, for example, you also have research coordinators, research study nurses. Some centers have additional scheduling staff that helps with the clinical trials. So, it’s really a way to get excellent quality clinical care, often getting access to cutting edge treatments.

And so, here at Dana Farber, for example, we try to have a clinical trial option available for patients at every stage of the disease, so that we have trial options for patients who have never had treatment for their CLL, trial options for patients who have maybe only had one or two prior treatments, and then some of those other more experimental clinical trials for patients maybe who have exhausted some of the other options that are available by the FDA-approved therapies.

So, I’m really a huge advocate for clinical trials. I think that’s how we’ll continue to improve the treatment options for our patients with CLL.

CLL Treatment Advances: What Do You Need to Know?

CLL Treatment Advances: What Do You Need to Know? from Patient Empowerment Network on Vimeo

Dr. Matthew Davids reviews promising chronic lymphocytic leukemia (CLL) research and shares online resources for patients to stay informed as treatments develop.

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Transcript:

Dr. Matthew Davids

So, this remains a very exciting time for CLL research. The last several years have witnessed the development of a number of these novel agent-based approaches, these oral drugs that target the different pathways inside the CLL cell that the cell survives with.

And so, we’ve really kind of reached the end of the beginning, as I call it, because the first goal, of course, was developing each one of these novel agent drugs on its own. We had to show first that they were safe and figure out what the dose was for patients, and then figure out that they’re effective on their own. And we’ve kind of checked those boxes at this point and reached a point where we have now several different novel agents that are FDA approved already for CLL patients.

And so, I think the big research challenge now going forward is kind of twofold. One is identifying the best combinations of these drugs to put together. And No. 2, identifying which patients will benefit most from which specific combinations.

And so, there’s a number of different clinical trials going on right now looking at these questions.

And just kind of highlighting some of them, one of them is the study of venetoclax with obinutuzumab that I mentioned before. We just had a pretty early readout from this study. But I think it’s gonna be very important to see how patients do over time after they finish the one year of therapy, and both for this study as well as another study called MURANO, which looked at the patients who had already had prior chemotherapy-based regimens and then received venetoclax, in this case with rituximab.

In both cases, when there’s time-limited therapy, I think a key research question is gonna be, when those patients do have progression of the CLL – hopefully years later – do they respond again to that same treatment? Can you use venetoclax again? And do the patients respond nicely? And if they do, then that could be a very nice intermittent treatment strategy to allow patients to be off therapy for a period of time, and then only to receive additional treatment when they need it.

I think another important and exciting area is the combination approaches. And I’ve talked about both ibrutinib and venetoclax as probably two of our most promising new drugs. And so, there are now a number of different studies exploring the combination of ibrutinib plus venetoclax given at the same time. And some of the initial data that’s been published looks very promising. This is a very well tolerated and highly effective combination in the initial studies. It’s all oral, which is nice. So, it’s just pills without the need for any infusions. And again, it’s designed to, hopefully, be a time-limited regimen, and patients hopefully will have a nice durable response after an initial treatment with these two drugs.

There are certainly a number of other drugs that are very promising as well. There’s a whole class that we haven’t talked about yet called PI3 kinase inhibitor drugs. We have two such drugs currently approved now for CLL patients, idelalisib and duvelisib. These drugs also are very effective for treating CLL but tend to have more side effects when they’re given as the first therapy. So, most patients will start with a different therapy. But then the PI3 kinase drugs can be a great option for patients who are in the relapse setting after they’ve had prior treatments.

And there’s another one in development called umbralisib, which also looks very promising and seems to perhaps be even the safest of these PI3 kinase inhibitor drugs. And that’s not yet FDA approved. But we anticipate it’s likely gonna get an approval relatively soon.

And so, combining these new PI3 kinase drugs also with venetoclax is an area of research interest, and a number of other combinations. As you can imagine, the longer the list grows of drugs, the more different combinations we can explore. And we’re trying to use the science from the laboratory to try to determine ahead of time what we think are the most promising strategies because we can’t do clinical trials of every single combination. But those are some of the sort of novel agent studies that I’m excited about right now.

I think the other area that could prove to be very helpful for our CLL patients is CAR T-cell therapy, which stands for chimeric antigen receptor T-cells. CAR T-cell therapy is a way to harness the body’s own immune system to fight cancer.

So, to do this, we would take cells out from a patient. And these are T lymphocyte cells. So, not the CLL cells, but a normal immune cell called a T lymphocyte. And then the cells get educated outside the body to recognize CLL cells more effectively. And they’re grown up and expanded and then reinfused into a patient, where they can go around and kill CLL cells. This can be a very effective treatment and can lead to complete remissions with durability.

And this approach is now in clinical trials. There are some risks to CAR T-cell based therapy. Something called cytokine release syndrome, where patients can get very sick, almost like they have a severe infection, but they don’t have an infection. There’s some neurologic risks to this as well that can be quite scary if they happen but in almost all cases are reversible. So, I think that this is an interesting area of research right now. It’s certainly not yet approved by the FDA for CLL. But we hope that, over time, as the CAR T-cell therapy becomes more effective and has fewer side effects, that eventually it will become a therapy option for patients who have had prior treatments for their CLL.

So, I think despite the fact that we’ve made a lot of advances in the last few years, we still have a lot of work to do in the research area to try to improve our treatments even further for our CLL patients.

So, in terms of how patients can stay informed about all these developments, it frankly is quite challenging, even for us in the field, to keep up with all of this. But there are some resources that can help. The first thing I would say is that the research tends to come along in fits and spurts, and one of the fits is generally the big research meetings where we all gather together to present our new data.

And probably the biggest highlight of the year is the ASH meeting, American Society of Hematology, which is usually in early December. That’s a good time to start looking on the internet for news about CLL, latest treatments, those sorts of things. Often, it’s kind of early December where we first hear about these breaking stories.

Another meeting that’s become big over the last few years is the European Hematology Association, which usually takes place in mid-June. And that’s, again, another time when we often see new data coming about. And one area where I would say this could be very helpful – or one website that I think is helpful – is the CLL Society website. This is led by Brian Koffman, who himself is a CLL patient.

And he kind of collates a lot of the information from these meetings and puts them in one place on his website. He’ll often interview CLL specialists to get their opinion about some of the newest developments. And so, I think Brian’s webpage, CLLSociety.org, can really be a great resource for getting up to date on the latest data.

There certainly are other websites out there now as well which are helpful. For example, another one that I’m working with closely is called VJHemOnc. And VJHemOnc comes to these big meetings, again, interviews a lot of the experts on their takes on the new data.

And I find that this platform in particular, the video-based platform, can be very engaging. It really forces us, as the investigators, to kind of hone down on what the most important key points are and give little snippets about that. And I would think that would be easier for our patients, in many cases, to digest, compared to some of the original papers themselves, which can be quite dense.

So, those would be my major resources that I’d recommend for CLL patients who are looking for additional information on the latest research.

CLL Treatment Decisions: What Path is Best for YOU?

CLL Treatment Decisions: What Path is Best for YOU? from Patient Empowerment Network on Vimeo.

 Dr. Matthew Davids discusses factors that can impact a chronic lymphocytic leukemia (CLL) patient’s treatment course, including genetic testing results, age and co-existing conditions. Want to Learn More? Download the Find Your Voice Resource Guide here.

Dr. Matthew Davids is the Associate Director of the CLL Center at Dana-Farber Cancer Institute. More about this expert.

See More From The Pro-Active CLL Patient Toolkit

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Fact or Fiction? CLL Treatment & Side Effects

 

CLL Genetic Tests: How Do Results Impact Treatment and Care?

 

Essential Lab Tests for CLL Patients


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Transcript:

Dr. Matthew Davids

So, there are a number of different factors that go into the decision of which of these regimens to choose for the initial therapy of CLL. One of them is certainly the age and fitness level of the patient and what other medical issues they have. So, as patients get above the age 65, they typically may have other medical issues and may not tolerate more aggressive chemoimmunotherapy-based regimens like FCR. But they could certainly tolerate the novel agent regimens like ibrutinib or venetoclax plus obinutuzumab.

Another consideration that comes into play is the biology of the CLL cells themselves. Some patients with CLL have a higher risk form of the disease. We call this either deletion 17p or TP53 mutation. And those patients typically do not benefit as much from chemoimmunotherapy.

So, even younger patients there, we think about a novel agent-based approach. And we have, again, the longest-term data on ibrutinib for that population, although venetoclax plus obinutuzumab is also a consideration.

And then as we think about debating between these different options, we also think about the specific other medical issues that a patient may have. So, ibrutinib does have some risks in terms of atrial fibrillation, which is an abnormal heart rhythm. It can cause patients to be a bit more prone to bleeding or bruising. And so, for patients who have these existing risks, if they have heart disease already, or if they’ve had issues with bleeding recently, ibrutinib may not be the best option, and venetoclax plus obinutuzumab would be appealing for a patient like that.

Now, with venetoclax and obinutuzumab, it can be such a potent regimen that it can break the tumor cells open too quickly. This is something we call tumor lysis syndrome. It’s not something we’ve seen commonly with this regimen. But we do watch patients very closely when they’re first dosing.And so, for example, patients who have poor kidney function might be at a higher risk for this side effect. And those might be patients, again, where we think about ibrutinib as a very good option, since it’s very well tolerated even by patients who have issues with their kidneys.

So, those are some of the factors that go into it. Certainly, patient preference makes a big difference. Some patients don’t mind the idea of going on a pill, and they like the idea that it’ll control their disease in the long term. And so there, a therapy like ibrutinib may make a lot of sense. Other patients may find that they prefer what we call a time-limited strategy. And using the venetoclax plus obinutuzumab makes a lot of sense there because it’s a one-year regimen, and they can stop. But we don’t know yet the durability of those effects. So, those are some of the factors that go into making this important decision as to what to receive for a first therapy.

I think patients have an increasingly large role in making treatment decisions about what they would like to receive, especially for their first therapy for CLL. It used to be that we had very limited treatment options for CLL, and really the only choice was chemotherapy. And so, that was a pretty easy choice if you had no other options.

So now, as I’ve highlighted, we have multiple different choices. We have chemotherapy-based approaches. We have novel agent approaches, both continuous and time limited. And so, I think it’s helpful for patients to educate themselves about the pros and cons of these different options, to get input from a CLL specialist, if possible, and certainly from their oncologist as well as family members and friends, particularly if they have had friends who’ve gone through this. Getting their advice can be helpful.

And reaching out to online supports as well can be a useful thing in terms of educating oneself. And at the end of the day, the patient has to make the decision as to what they think is best for them.

And it might be a different decision for each individual patient. But the good news for patients, even though it can be challenging to make this decision, all of these options are good ones. And so, there isn’t really a wrong decision here. But there may be some that are better suited for individual patients based on their own preferences.

CLL Treatment Options: What’s Available NOW?

CLL Treatment Options: What’s Available NOW? from Patient Empowerment Network on Vimeo.

Dr. Matthew Davids reviews current chronic lymphocytic leukemia (CLL) treatment approaches and discusses the role of watch and wait.

Dr. Matthew Davids is the Associate Director of the CLL Center at Dana-Farber Cancer Institute. More about this expert.

See More From The Path to CLL Empowerment

Related Resources

Fact or Fiction? CLL Treatment & Side Effects

CLL Genetic Tests: How Do Results Impact Treatment and Care?

Essential Lab Tests for CLL Patients


Transcript:

Dr. Matthew Davids:   So, we’re very fortunate in CLL that we have a number of very effective treatment options. But I would like to start by highlighting the fact that, for the majority of CLL patients when they’re first diagnosed, a watch and wait or observation strategy is generally preferred.

And this goes back to many years of research showing that there’s no survival advantage to starting early with chemotherapy-based approaches.

And we have some recent data with the newer drugs that, even with these better agents in terms of the tolerability, that early intervention strategies still probably don’t make a difference for our patients and are associated still with side effects and risks. So, the first important thing is to understand that it’s okay to be observed and go on to this watch and wait strategy, and that many patients can stay on this type of approach for many years.

However, once treatment is indicated, we do have a number of therapy options for CLL patients. And these go back to chemotherapy-based approaches, which have been around for quite a while now and now include some newer drugs that we call novel agents that are really transforming how we manage the disease. So, for younger, fitter patients, we can still think about chemoimmunotherapy, and in particular a regimen called FCR, which includes two chemotherapy drugs, fludarabine and cyclophosphamide, and a third drug which is an antibody called rituximab.

And this combination works very well, in particular for patients who are very fit and can tolerate it and remains a viable option. An advantage of this approach is that it’s time limited. It’s a six-month course. But there are some significant side effects from chemotherapy and some longer-term risks. And so, it’s something that we think carefully about before we recommend.

We really think about the novel agents now as being a good option for most of our patients with CLL. And these novel agents are typically pills that, in general, tend to be well tolerated, although each one has its unique risks and potential side effects. We’ve been using the drug ibrutinib now for a few years for the initial treatment of CLL. And this drug targets one of the pathways in the CLL that the cell relies on for its survival. And it’s a drug that patients take once per day. And once they start on it, they usually continue on it for a long period of time. We’ve had patients on this drug up to seven or eight years now who continue to do well.

Ibrutinib doesn’t tend to completely eradicate the CLL. But it often gets patients into very good remissions. And if they tolerate the drug well, then they can stay on it long term and control the disease. But typically, the drug is given as a continuous therapy. So, we don’t have as much experience with stopping it at this point. And so, that’s typically how we recommend giving it, is as a continuous drug.

Now, another new option for the initial therapy of CLL patients is called venetoclax, which is another pill that we have had a lot of experience with over the last few years in clinical trials. It was approved for patients who had previously had treatment for CLL for the last three years or so. And then just recently, the FDA gave approval to venetoclax as a first therapy for CLL patients. And we typically give this in combination with a different antibody drug called obinutuzumab, which is given intravenously.

So, this regimen, which we call venetoclax plus obinutuzumab, is typically given for a six-month combination course, followed by about six additional months of venetoclax pills. And then patients stop therapy at that point.

So, one of the advantages of this approach is that, like the chemotherapy, it’s a time-limited approach for one year. And we can often see very deep remissions that allow patients to remain off therapy for a period of time afterwards.

One of the issues so far is just that we don’t have as long-term follow up as we do with ibrutinib. So, we don’t know what’s gonna happen to these patients seven or eight years after they’ve started venetoclax plus obinutuzumab. We certainly hope that this one year of therapy provides a durable response for patients, and it certainly looks promising in that regard so far. But we currently have more long-term experience with ibrutinib as an initial treatment.

So, these are kind of the main options that we think about for patients who need their first therapy for CLL. We always think about observation first. But when patients do need treatment, we move toward either a chemoimmunotherapy-based approach with a regimen like FCR, or ibrutinib, or venetoclax plus obinutuzumab. And so, it’s great to have all these very valuable and effective options for our patients.

How is a CLL Treatment Path Determined?

How is a CLL Treatment Path Determined? from Patient Empowerment Network on Vimeo.

Dr. Danielle Brander explains the patient-specific factors and disease-specific factors that are taken into consideration when determining a treatment approach for people with CLL.

Dr. Danielle Brander is Director of the CLL and Lymphoma Clinical Research Program at Duke Cancer Institute. Learn more about Dr. Brander See More From the Path to CLL Empowerment


Transcript:

Dr. Brander:

There are several factors to take in consideration when discussing individualized treatment approaches or options for patients.

Broadly, this can be divided into patient-specific factors, and then CLL-specific factors. And what I mean by that is patient’s age, even for patients very fit, we know from clinical trials that there’s a different processing, tolerability, and benefit of certain chemotherapies and a higher risk of certain side effects, even with the novel therapies as patients advance in age.

There are other patient-specific factors such as there are other medical problems. We often call these comorbidities. These are things like cardiovascular or a heart problem history, diabetes, kidney function differences. A lot of those factors play into individualizing when you know different treatment side effects what might be the best option for patients.

In the CLL-specific factors, these are some of the markers and characteristics that we have talked about in terms of FISH testing, TP53 mutation status, and IGHV mutation status. Based on recent clinical trials for patients receiving first treatment, if there are any changes, which historically chemotherapy didn’t treat the CLL for as long as we would have liked, we tend to err towards the novel agents for sure. And even across all markers, there can be a benefit of the newer drugs such as ibrutinib or venetoclax, or many of the other next-generation inhibitors that are in development. But for sure, patients with deletion 17p or TP53 mutation should never receive chemoimmunotherapy.

There’s a lot of research going into understanding what other CLL-specific markers may benefit for one treatment type versus the next. And we hope that all patients could potentially benefit from clinical trials both in the options that are offered as well as some of this other testing, which is how do you determine which markers are important for patients in the era of the drugs that we have today.