Minimal Residual Disease (MRD): What Does it Mean for You?

Minimal Residual Disease (MRD): What Does it Mean for You? from Patient Empowerment Network on Vimeo.

Dr. Matthew Davids defines the term minimal residual disease (MRD) and explains its role in managing chronic lymphocytic leukemia (CLL).

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

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Transcript:

Dr. Matthew Davids

So, one term that patients often come across when they’re looking online that they might not know exactly what it means is so-called MRD. This stands for minimal residual disease.

And MRD is increasingly becoming an important endpoint in our trials, meaning that it’s a test that we rely on to try to make decisions about treatment in the trials. And we’re hoping that this will be a strategy that we can eventually use in regular clinical practice.

So, what is MRD? Basically, MRD is a way to look, at a very, very molecular level, at tiny, tiny amounts of the disease. And this a feature of the fact that we have very effective treatments for CLL, and so we can give various treatments, whether it’s chemoimmunotherapy or drugs like venetoclax, for example. And then we can look under the microscope in, for example, the bone marrow tissue, and we might not see any CLL cells. So, we might call that a complete remission.

But often, there’s still evidence of molecular disease left behind that we can’t see under the microscope, but we can use very sophisticated biological techniques to actually detect what we call MRD. And we find that, if there is MRD present, that patients don’t tend to have as durable of a remission compared to when MRD is so-called undetectable.

So, it’s a very important term to understand. When patients get to an undetectable MRD state, that’s a very good thing. It means that they’re likely to have a very long response to whatever therapy they had. But you also have to remember that MRD itself has its limits of what it can detect. And so, just being undetectable for MRD does not mean that you’re necessarily cured of the CLL.

And there are patients who have undetectable MRD who later do have a recurrence of the CLL. But it does help us guide the treatment in terms of knowing that patients are in a good remission, that they may be able to stop the treatment that they’re on and enjoy a long response without the need for ongoing treatment.

But eventually, for most CLL patients, the disease will come back. And we can detect that sometimes with this MRD test as well. And that’s an interesting research question ongoing as to whether we should intervene at that point to restart therapy when we first see the MRD test become positive again. And hopefully, that’s something that we’ll continue to learn about as we further explore that question in clinical trials.

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.

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

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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 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.

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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.

Chronic Lymphocytic Leukemia (CLL) Defined

Chronic Lymphocytic Leukemia (CLL) Defined from Patient Empowerment Network on Vimeo.

What is CLL? Dr. Brian Hill defines chronic lymphocytic leukemia (CLL) and explains how it differs from small lymphocytic lymphoma (SLL).

Dr. Brian Hill is the Director of the Lymphoid Malignancies Program at Cleveland Clinic. More about this expert.

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Transcript:

Dr. Brian Hill:

So, chronic lymphocytic leukemia is a term that refers to a cancerous condition in which the abnormal or cancerous white blood cells are a type of B-cells with certain characteristics that are present above a certain threshold in the blood. Those same cancer cells can also grow and divide and set up shop in other organs besides the blood and bone marrow.

And that can be a lymph node, spleen and sometimes we find the exact same type of cell in a lymph node or other parts of the body. And we don’t find it in large quantities enough in the blood. And when that happens, we call it small lymphocytic lymphoma or SLL. So, people get very confused by the terminology, “Do I have leukemia, or do I have lymphoma.” And so, a lot of times there’s a reference to a condition called CLL-SLL. CLL-SLL really is one disease.

And the term leukemia or lymphoma really just refers to where is the predominant location for the abnormal cancer B-cells. Are they in the blood or are they in the tissue?

If it’s in the blood, mostly above 5,000 cells per microliter, that’s the cut off. If it’s in the blood predominantly, it’s CLL. But if those same cells are in the lymph nodes or the spleen but not above that threshold of 5,000 in the blood, then the term is small lymphocytic lymphoma. And often times that diagnosis made from a tissue biopsy or a lymph node biopsy rather through a blood test or a bone marrow biopsy. Really, these are the same disease. And even physicians who don’t practice in this area get confused about it.

And it’s important to know that they can be treated exactly the same and are interchangeable. Rarely I’ve seen a mistake be made that someone who has a diagnosis of SLL or small lymphocytic lymphoma is treated with the types of chemotherapy drugs that we would typically use for indolent forms of lymphoma.

And some of those therapies overlap. So, there are biologic similarities and clinical similarities between B-cell lymphomas and CLL-SLL for sure. But there is a lot of nuance in B-cell lymphomas, and not every single treatment that works really well for B-cell lymphoma should be used in CLL or SLL.

You’re Not a Guinea Pig: Understanding Clinical Trial Participation

You’re Not a Guinea Pig: Understanding Clinical Trial Participation from Patient Empowerment Network on Vimeo.

“Will I be a guinea pig if I participate in a clinical trial?” CLL expert Dr. Brian Hill explains the clinical trial process and addresses common patient fears and misconceptions.

Dr. Brian Hill is the Director of the Lymphoid Malignancies Program at Cleveland Clinic. More about this expert.

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Transcript:

Dr. Brian Hill:

So, one of the first questions many people ask about being a clinical trial participant is, “Am I a guinea pig?” And what I would say is we’re always practicing medicine. Anything we do, we’re practicing.

But we are always trying to get better whether it’s formally on a trial or not. In terms of side effects of treatment, no matter what – if we have the treatment available, any medication can potentially cause side effects. And it’s very difficult to predict. So, even if you are not on a clinical trial, you could be treated with a standard therapy and potentially have problems or difficulty with it. In terms of clinical trials, it depends where in the sort of journey you are in. If you have never been treated before and now you need to be treated, there are trials that are appropriate for people who are at their first line of treatment.

And this is not typically where we are experimenting with new drugs. So, this is typically where we have established treatments or just sort of trying to compare which one is better. Sometimes these are randomized.

So, there’s a flip of a coin, and you can be assigned to one or another. And I understand why many patients may not want to have their treatment determined by chance. But I would keep in mind that usually if this is being done, it’s been vetted through not just the institution where they are being treated, but often times through review boards throughout the country who basically say, “We think it’s okay to have a flip of a coin decision here because if we have a great treatment which is A and a great treatment which is B and we really don’t know if A or B is better, it’s okay to sort of have a randomization where you may get A or B.”

Sometimes A is the standard and B is likely to be better, but we don’t really know that B is better. And the only way to get the second option would be to be on the clinical trial. So, in that case if you are enrolled, the “worst” option would be the standard.

But it may give you the option of being even better than the standard. And again, if we knew that the second option was better then it wouldn’t be a clinical trial, it would be our standard.  This is sort of how we make progress. And it requires a buy in from the medical community and physicians, but also, it’s important that patients feel comfortable with it. So, that’s kind of for front line treatment. In terms of subsequent therapies, again there are a lot of very good standard treatments available.

And sometimes there are new drugs that are being developed. If the new drug has never been given before to a human, that’s called a Phase One trial. And typically, those are given or offered to people who have had many other lines of therapy and may not have other good options. But sometimes we know that the new drug has been given to people, it’s safe.

The side effect profile is already known even if it hasn’t been given to large numbers of people. And in those cases that would be something around something often called a Phase Two trial where we know it’s safe, but we’d love to see how well it works. And that’s an option for patients as well.

Right. So, outside of talking with your hematologist/oncologist or CLL specialist, there are many other resources for getting information about CLL. The Lymphoma Research Foundation, The Leukemia Lymphoma Society and the CLL Society are all great organizations that have useful websites.

They have 1-800 numbers you can call into. Many of these groups have – I know the CLL Society has a support group in many cities that’s held on a regular basis. And often times there are patient meetings organized through LLS or LRF, the two groups that I mentioned, that allow patients to come and learn from each other and also ask questions of specialists who may be speaking at those events.

An Overview of New CLL Treatments

An Overview of New CLL Treatments from Patient Empowerment Network on Vimeo.

Are there new CLL treatment approaches that patients should know about? Dr. Brian Hill reviews the “explosion of new treatments” in the past few years.

Dr. Brian Hill is the Director of the Lymphoid Malignancies Program at Cleveland Clinic. More about this expert.

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Transcript:

Dr. Brian Hill:

So, there’s been an explosion of new treatments for CLL just in the past five years. As of before 2014, most of the treatment we had involved both traditional chemotherapy drugs with antibodies.

Those antibodies include Rituximab and more recently other antibodies such as obinutuzumab. The explosion that I’m referring to is really in the development of very effective and generally well tolerated targeted agents. The most well known in the first one of these was Ibrutinib which inhibits a protein that tells the CLL cells to grow and divide called BTK. There are other blockers or inhibitors of BTK that are now approved include Acalabrutinib. The side effect of these are slightly different, and there are reasons why you might choose one or the other.

There’s also a very potent medication called Venetoclax which is now used – which has a different mechanism of action than BTK blockers.

Many of these work better when you combine them with the antibodies I mentioned. And so right now a lot of the research that’s ongoing is examining the utility of combining these agents or how to best sequence them. So, much of the decision about how we can best treat patients is derived from really well done, well designed clinical trials. And sometimes clinical trials can give patients an option that’s not yet a standard but is likely to become a standard.

Or it can give you access to a drug that is promising and not yet widely available. So, there are definitely times to seek – at least ask the question whether a clinical trial is a good option or the best option.

And there may be times where it is not appropriate, and the standard treatments are very reasonable and may require fewer visits to a referral center to be treated. So, I think it’s worth having that conversation both with the primary hematologist/oncologist as well as the CLL specialist.

Not to Worry! Your Guide to Watch and Wait

Not to Worry! Your Guide to Watch and Wait from Patient Empowerment Network on Vimeo.

 Watch and wait, or active surveillance, often feels like watch and worry to CLL patients. Dr. Brian Hill provides a comprehensive guide to the period of time before CLL treatment begins and shares approaches for managing anxiety.

Dr. Brian Hill is the Director of the Lymphoid Malignancies Program at Cleveland Clinic. More about this expert.

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Transcript:

Dr. Brian Hill:

So, watch and wait is the term that’s referred to for not actively treating a patient with CLL after the diagnosis. As many people probably out there watching know, the diagnosis of CLL is often made incidentally or accidentally through routine laboratory tests that are done for some other reason.

Maybe they are going to have surgery. Or maybe they are going to have just a primary care checkup. And blood count shows too many white blood cells. And everything else is fine. The patient feels normal. There’s no symptom. But it leads to a referral usually to a hematologist who then does more testing and makes a diagnosis of chronic lymphocytic leukemia. The word leukemia is very scary because it often conjures up images of acute leukemia which is a disease that can make people very sick very quickly.

We’re taught in much of medicine and in much of cancer that early diagnosis and early treatment is very important. And it is very important for many conditions – breast cancer or we’re taught let’s get our mammograms.

And have an early detection and immediate treatment to cure the breast cancer. Similarly, colon cancer – get your colonoscopy, get your diagnosis sooner rather than later. And have surgery so you can have a higher likelihood of a cure. In the case of chronic lymphocytic leukemia, it’s never been shown despite multiple attempts over many decades, that treating someone with CLL is – earlier, is going to impact the outcomes and the big picture. But we do know that treating CLL earlier can lead to more side effects earlier.

So, in other words, if you feel fine and your blood counts are just a little abnormal, and there’s not compelling indication to treat, we can safely observe patients until an indication for treatment exists. And what I tell patients is that if we treat today, the treatment will work.

If we treat tomorrow, the treatment will work. And if we treat in five years, the treatment will work. So, there’s – we have very good evidence that delaying treatment until you need it does not compromise the likelihood of the treatment working. So, it’s a little bit of a different mindset from other types of cancer where we are taught to treat early and immediately. So, a lot of times people will call it watch and worry instead of watch and wait, and there’s a lot of anxiety about that.

Again, their diagnosis has the word leukemia in it. It can be a very scary time. And it takes a little bit of trust to be convinced that you don’t need to be treated just because you have it. And that’s often times when we do get second opinions if the first hematologist/oncologist says it’s okay to watch it and wait. We don’t need to treat. A lot of the time people then seek another opinion to confirm that’s accurate. And in most cases – I would say 90% of the time when I’ve had a second opinion for a patient who’s been recommended to watch and wait, I typically concur with that recommendation.

So, during watchful waiting or – I like to call it active surveillance because it’s not that we aren’t doing anything, we are surveilling or monitoring. And the two things that we monitor are symptoms and blood counts. So, it sort of begs the question that many people ask which is, “If you are not going to treat me now, when will you treat me? When will I need to be treated?” And the first indication – the first thing we look at is symptoms. So, if you have symptoms of significant fatigue to the point where you are really having a difficult time functioning.

Or if you have drenching night sweats that wake you up from night and make you change your nightclothes. Those type of symptoms would push us to treat. So, those are the things that are being asked of patients at their regular follow up which is usually every two or three months initially.

And sometimes can be spaced out to every four to six months if things are stable. But usually during the first year you want to be checking on folks every two to three months. Weight loss would be another symptom to look out for – sort of unintentional weight loss. The other thing we monitor is the blood counts. So, with a simple CBC or complete blood count, we can see what is happening with the white blood cell count which may and often goes up.

And a lot of folks focus on the white blood cell count and its trajectory and how that is rising. Some people’s white blood cell count can fluctuate. Others can stay relatively flat. And some people do have a continued rise on the white blood cell count. The white blood cell count in and of itself is not the final reason to recommend treatment.

But with time, as the white blood cell count goes up, we sometimes see the other numbers going down. And actually, the other numbers going down are the ones that are more important. Those numbers are – the red blood cell count measurement which is usually measured by hemoglobin concentration or hematocrit. And then the other is the platelet number. So, if either the hemoglobin or the platelet number gets below threshold, those are typically indications for treatment.

So, during this period of observation or active surveillance – watchful waiting, whatever term you choose. This can go on for years.

And it can be associated with anxiety. So, trying to do things to cope with managing anxiety is important. Other things that many people are interested in are – is diet. So, do we know of a particular food or food group that we should focus on? Or is there something we should avoid? And the short answer to that is that many – it’s a difficult topic to study. As you might imagine, diet can be so varied around people. And in a typical week the average person eats so many different types of foods that it’s difficult to focus in on one particular thing.

What we can say is that in general for health, clearly fresh fruits and vegetables are the best source of nutrition. And also, are best for your health.

Avoiding processed foods and processed meats and other foods that are high in saturated fats is probably important in general for your health. Although we can’t say specifically that it’s definitely going to make an impact in the white blood cell count or the trajectory of the CLL. In terms of supplements and natural products, many people are interested in this topic. And again, it is a difficult one to study. Some of the natural products out there are purified forms of things from plants and other ingestible herbs and so forth.

But the problem is, is that if you take any component – even if it’s natural occurring, take it in large quantities it can lead to other problems. There was a well-known study from – that studied the impact of green tea extract on the white blood cell count.

And if you took large quantities of green tea extract, it seemed as if it did sort of lower the white blood cell count a little bit. But some people also had abnormalities of their liver function as a result. So, I don’t recommend green tea extract. And I instead say, “If you like tea and you want to drink green tea, I think that’s probably fine.” But I wouldn’t do it in excess. And just maybe try to incorporate it into a balance diet otherwise.

Overwhelmed By a CLL Diagnosis? Key Steps to Take

Overwhelmed By a CLL Diagnosis? Key Steps to Take from Patient Empowerment Network on Vimeo.

CLL advocate Dr. Brian Koffman, outlines key steps to take following a chronic lymphocytic leukemia (CLL) diagnosis.

Dr. Brian Koffman is the cofounder, chief medical officer, and executive vice president of The CLL Society.

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Transcript:

Dr. Koffman:             

When somebody’s starting their CLL journey, there is some advice that I’d like to give people. The first is take your time. CLL rarely needs to be treated as soon as it’s diagnosed. You have time to learn about the disease, to familiarize yourself with the disease, and that learning is an iterative process.

You go over and over stuff, and eventually, this incredibly foreign language full of acronyms and medical talk becomes more familiar to you, and you feel more comfortable with it. But, it’s very overwhelming at first, but it’s not like some acute leukemias and other kinds of cancer, where they’re gonna see you on Tuesday and book the start of therapy on Friday. In CLL, that almost never happens. So, the first thing I would say is take a deep breath, under-react, and accept that you’ve got some time to make that decision.

The second strong piece of advice I would give people is to get an expert on your team. I can’t emphasize that enough. CLL is a rare cancer that the treatment paradigms have shifted radically in the last couple years, and they’re continuing to shift. And, if you’re not taking advantage of those changes – and, the research shows that in the community, patients are still too often getting inappropriate or less-than-optimum care compared to what’s happening in academic research centers.

You wanna get into their Rolodex file. You wanna be in their system so if a crisis happens three years down the line, you’re not a new patient trying to get an appointment. You have them in your system.

A third point that I’d make is to insist that you get appropriate testing before each and every treatment of your CLL. “Test before treat” is one of our mantras at the CLL Society because CLL tends to evolve over time, and not some – most, but not all of the prognostic and predictive factors can change over time, and those factors can be very influential in terms of saying, “This therapy will work, that therapy won’t work.” It’s critical that you know that, and if you knew it a year ago, it may be different now, so it’s critical to insist that your doctor do the appropriate predictive and prognostic testing.

We outline that on our website in our “test before treat” section in terms of what tests you need to have done. Take your time, get an expert, and get tested before treatment.

So, one of the questions I get asked is how can people learn more about CLL?

So, you can – some people like to learn online. CLLSociety.org has highly curated, medically reviewed articles that can help people from the beginning move forward. Leukemia and Lymphoma Society has useful resources on their website and has pamphlets that can help. Lymphoma Research Foundation is another. The Patient Empowerment Network offers you resources, listening to CLL experts and other CLL patients.

Going to support groups – you can often learn from other patients’ experiences. There’s nothing like meeting another patient and finding out what they’re like in that journey, especially if you’re two months into the journey and they’re 15-20 years into the journey. That can be incredibly helpful for you to see what their personal experience was in doing that. So, and also, there’s educational forums – for example, at the CLL Society, we have a dozen educational forums across the country every year – that give people an opportunity to learn from experts at places like the National Institutes of Health, Dana-Farber, MD Anderson, UCSD, and the Mayo Clinic.

So, we usually have one that isn’t far away from people to be able to go to if you wanna do your learning live.

How Can Patients Learn About Developing CLL Research?

How Can Patients Learn About Developing CLL Research? from Patient Empowerment Network on Vimeo.

Dr. Danielle Brander explains why it’s important for chronic lymphocytic leukemia (CLL) patients to stay up-to-date on developing research and treatment news. Dr. Brander also shares resources for learning more about clinical studies.

Dr. Danielle Brander is Director of the CLL and Lymphoma Clinical Research Program at Duke Cancer Institute. Learn more about Dr. Brander here.


Related Programs

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

Essential Lab Tests for CLL Patients

How Can Patients Advocate for Genetic Testing?


Transcript:

Dr. Brander:

I think it’s very important that patients and their caregivers stay informed and advised of opportunities to participate in ongoing research. I think there’s a misconception that with all the favorable progress in treatment options available for CLL, that there’s no longer the need for clinical research participation.

Though, there are a lot of novel options available for CLL, there’s still a lot of ways that we can improve care for patients. That is, there are trials with the next-generation inhibitors or for patients traditionally with harder to treat CLL or may become resistant to the novel agents, there’s a lot of trials looking into how do you combine the novel agents to give patients the best options. And then a lot of the research, too, are not just in the treatments.

But as our science advances into looking at other markers of the CLL cells, or what we call the depth of response, how much CLL you kill with the treatments and how low of a level we can get in terms of detection. This may result in a situation where patients have the opportunity to receive novel treatments, have a really good response, and then potentially stop the treatments and be followed off of therapies, so have the benefit of novel treatment but not with having to go on an ongoing drug forever and ever.

When I talk to a patient about opportunities for clinical trials, I’m really focused on the patient in front of me. That is, I wouldn’t offer or talk about a trial if I didn’t think it potentially could benefit the patient in front of me.

And again, though we’ve had a lot of advances in treatment options, there are certainly a lot of ways that we can engage and hopefully help patients moving forward. There’s been recent studies across all cancers showing that unfortunately a very low percent of patients are offered and enrolled and participating in clinical research studies, and I think it’s really important that patients know there’s a lot of opportunities out there that potentially could benefit them.

The different ways to be advised and informed, again, are some of the resources online educationally for CLL and lymphoma that often post about different sites for clinical trials. There’s a clinical trials.gov web site that all sites in the United States that are enrolling trials with patients have to log clinical trials, and though that has to be updated, it often can be a good beginning site.

But in the end, hopefully the best resource is your treatment team, your oncologist, and your other team that can help point you to what trials might be eligible for you, either at the location where you are or close by.

The last part I’ll point out is though we focus a lot on the treatment clinical trials, in CLL, where patients don’t always need treatment right away or may have treatment and have a response and then have a long period of time afterward, is that many centers are helping to engage patients in research that is not necessarily done during the time of their treatment. Again, to try to understand why some patients have a longer course until they require treatment, or why they might have responded differently, or other ways we can improve their care.

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 here.


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.

Essential Lab Tests for CLL Patients

Essential Lab Tests for CLL Patients from Patient Empowerment Network on Vimeo

See More From The Path to CLL Empowerment

Dr. Danielle Brander provides an overview of essential lab testing for chronic lymphocytic leukemia (CLL) patients and discusses which tests should be repeated over time.

Dr. Danielle Brander is Director of the CLL and Lymphoma Clinical Research Program at Duke Cancer Institute. Learn more about Dr. Brander here.

Related Resources

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

What is Personalized Medicine?

How Can Patients Advocate for Genetic Testing?

 


Transcript:

Dr. Brander:               

So, there are additional laboratory tests besides the genomic or the prognostic markers that patients should have at the time of diagnosis. One that all patients have is a test called the flow cytometry, and that is done often for CLL patients on the peripheral blood. It may also be done on the lymph node or the bone marrow. And this is a profile of the surface of the cells that help your pathologist and your oncologist to confirm that this looks like CLL.

So most patients when they’re told of the diagnosis will have this either from the blood or it’s found on the lymph node. Notably, it’s not required in all patients, and most patients, in fact, to have a bone marrow biopsy at the time of diagnosis unless there’s a concern about other blood counts being low, and it’s not clear why that is going on.

Most of the other tests besides the prognostic genomic genetic markers that we talked about such as FISH, or IGHV, or TP53 are routine tests. So patients will have a repeat blood count, and this should be a blood count with a differential of the white blood count. CLL is a problem of a type of white cells called lymphocytes. So on the differential of the types of white cells you’ll see the lymphocytes are usually marked clearly elevated. But the differential also makes sure that there’s no low other white blood cells such as neutrophils, which are important in fighting bacterial infection.

It’s also a good idea to have at the time – and most patients will – a baseline chemistry, which include the kidney and the liver function. Though definitely not common, some patients can have involvement of CLL of the liver or kidneys.

This is pretty rare, especially around the time of diagnosis. It’s helpful to have those baseline tests. It’s also helpful because the median age of diagnosis of CLL is usually the early 70s, and so a repeat of the baseline kidney and liver function might find other chronic health problems that are important to know moving forward.

Some of the other tests, baseline labs, are more patient specific, and might need follow-up. For example, if the blood count revealed anemia, which is a low hemoglobin or hematocrit, the cells that carry oxygen, your treating team might want to order additional tests for anemia and make sure that the anemia isn’t due to something totally unrelated to the CLL such as iron deficiency or B12 deficiency, etc. So, there might be additional lab tests depending on the additional screening tests that are obtained at that time.

One other test that I’ll – or two other tests that I’ll mention at diagnosis, 1.) Is immunoglobulins, mostly for patients that have had a problem with recurrent infections because patients can have low antibody levels associated with CLL, even if it’s not been treated. So, your team – if recurrent infections have been a problem – may check for those antibody levels, those immunoglobulin levels. A second test that can be helpful at baseline is a test called SPEP or serum protein electrophoresis, which looks for extra proteins in the blood. And again, this can be seen with CLL and other lymphomas, and especially depending on patient’s symptoms, your physician, and treating team might want to obtain those labs.

Again, there are good resources online including the NCCN, CLL and leukemia patient-specific sites that might give a better outline beyond what we can cover today of tests that might be helpful in your specific case.

There are labs and tests in CLL that are repeated over time. Two of the common ones obtained at baseline, the complete blood count and the chemistry, will usually be repeated at every visit after diagnosis for patients not being treated at the time of diagnosis. They’re part of the monitoring, so every three or four months after you’re diagnosed when you see your oncologist and you have an exam, your history of how you’ve been doing, and labs taken, the white count and the chemistries are all to be followed with time.

At the time of treatment, there’s often additional tests that might be done depending on the type of treatment you’re receiving to make sure you don’t have a specific risk for recurrent reactivation of infections, for example. So the testing might change at the time of treatment. And specific to the prognostic biomarkers, the genomic or genetic testing of the CLL that we mentioned, some of them are repeated with time and some aren’t. The FISH, which is obtained at the time of diagnosis is recommended to be repeated. If patients have treatment, the CLL goes into response, and then relapses because the FISH testing can change with time.

The IGHV mutation status, however, as long as it was felt to be an adequate appropriate sample, is a characteristic of the leukemia that doesn’t change with time and would not be repeated. Similar to FISH, it’s a good idea to test the TP53 at the – not always at the time of diagnosis, but before treatment to make sure there’s not TP53 mutation.

But then similar to FISH, if the CLL goes into response and relapses, it’s advisable to repeat the TP53 as that can change as patients have different treatment options and they both help to, as mentioned, inform the first treatment. They’re also helpful to have in mind as patients are being followed on treatments because some patients have a higher risk of the treatment to stop working, for example, if there are higher-risk genomic changes.