What Should CLL Patients Know About Their Blood Work?
Ask the CLL Expert
Ask the Expert: What Should CLL Patients Know About Their Blood Work? from Patient Empowerment Network on Vimeo.
CLL experts Dr. Susan Leclair and Dr. Justin Taylor discuss how to understand testing with CLL, how CLL patients can advocate for the correct testing, making the most of doctors’ appointments, and more.
Transcript:
Andrew Schorr:
And hello from Southern California. I’m Andrew Schorr. Welcome to this Patient Empowerment Network program produced by Patient Power. We’re so delighted you are here. I’ve been living with CLL since 1996. And so, testing was not as sophisticated then, and it’s come a long way and there are a lot more choices now. So, in this program, we will be discussing how do you know when you need treatment? What tests are important when you’re in a sort of watch-and-wait period? If you start treatment, how do you know if it’s working? How it’s monitored? If you’re in remission? How do you know how deep that remission is? Should you need treatment again, are there other tests that need to be repeated, or new tests to be done? Lots to talk about. I want to thank the Patient Empowerment Network for putting this all together, and for their financial supporters who have no editorial control, that is AbbVie and Pharmacyclics. So, thanks to them for supporting patient education. Okay. If you have a question, send it to cll@patientpower.info. Many people have, so we got tons of questions, and we’ll get through as many as we can in this Ask the Expert program, helping all of us with CLL understand our blood work and what’s needed and when. And we have some great guests with us. First of all, I wanna go to my dear friend who I’ve know most of these 20-plus years as I’ve been living with CLL, Dr. Susan Leclair, laboratory science guru. She joins us from Dartmouth, Massachusetts. Hi, Susan.
Dr. Leclair:
Hi.
Andrew Schorr:
Welcome back to our program.
Dr. Leclair:
And I think we were both very young when we first met.
Andrew Schorr:
Well, you didn’t have grey hair. But I cannot say that I had a full head of hair, but here we go. And I didn’t lose it because of chemo. It was gone, hereditary. Okay. And now let’s scoot down to New York City to one of our top cancer centers in the world, Memorial SloanKettering, where we’re going straight to the lab. And that is Dr. Justin Taylor, laboratory researcher, and also CLL clinician. Justin Taylor, thanks for being with us.
Dr. Taylor:
Hi, Andrew. Thanks for having me. Happy to be here.
Andrew Schorr:
We’ve been wanting to get you with us for a while. And he, folks, is where action happens. They start with mice, and then they start working on what does it mean to all of us with our blood? And, of course, human clinical trials, and Memorial Sloan-Kettering has helped lead the way. Okay. Susan, are you ready to go?
Dr. Leclair:
Sure.
Andrew Schorr:
Okay. So, people worry, what about their tests? And one thing I wanna get off our plate right away, and I’ll just say it for me. So, I get immunoglobulin infusions once a month to boost my immunoglobulins. And you can help us understand what that is. And I get a blood test at the same time. And I worry if the platelets go up a little, or the platelets go down a little, or and then there’re all these MCVs and blah, blah, blah. I don’t understand what they mean. And I worry sometimes if there’s a little blip. But we really worry about—we’re not even worried. We watch the trend, right?
Dr. Leclair:
Right. I would not panic unless you see two consecutive numbers going in the same direction. Now there are a lot of caveats to that, but we don’t have five days on the program. So, basically, statistics don’t work, unless you’ve got at least three values. So, if you started at a value of 1.0, and the next time you got it, it was 1.5, and the next time you got that same test it was, I don’t know, 0.62, they’re not in the same direction. There’s no big change. You’re kinda okay.
You begin to worry only if it goes from a 1.0 to a 2.5 to a 5.0. Now you’re beginning to get a sense that things might be moving in a specific direction. So, you wanna wait. I know it’s not watch-and-wait; I know it’s watch-and-worry. But you have to wait for at least the third one of the values. It’s part of the reason that your physician will use that horrible word, “Fine,” when they look at things, and they say, “Oh, no, this looks fine.” It’s because they’re not seeing that trend going in one direction or another.
Now some tests, you want the trends to be higher; some you want lower. But think about you need three values going in the same direction in a row before something can be considered worthy of, well, worry, or at least worthy of a question.
Andrew Schorr:
Okay. Thank you for that. Justin, I wanna ask you about something we talk about a lot now in CLL, and as you get to the different chromosomal deletions, I guess you call it. So, we’ve known for a long time that one that led to more aggressive CLL was the 17p deletion.
Dr. Taylor:
Yes.
Andrew Schorr:
And now we have medicines that kind of work on 17p, which is cool. So, we got a question from Robert Schneider who said on the CLL patient with 17p, been treated in his case with Venclexta or venetoclax for two years, and had reached MRD, minimal residual disease negative in my bone marrow and blood, what are the pros and cons of stopping treatment if I’ve had this 17p? So, where are we now measuring 17p? And help us understand this MRD level.
Dr. Taylor:
Okay. Yeah. Lots of great points there. I’m glad you brought up the 17p. That is historically a more bad prognostic marker, although as you’ve brought up, we now have drugs that can work for patients with 17p deletions. So, we’re very excited in the clinic to have Ibrutinib and Venclexta, or venetoclax—I’ll use the generic names—as options for our patients with 17p deletions, or other abnormalities that include genes on 17p such as the p53 gene.
And so, those are effective. And we’ve seen some patients that have been lucky, as David, to get into a minimally residual disease, or measurably residual disease negative state from these treatments. But I’d say it’s still the level of our knowledge, at this time, does not allow us to know whether it’s completely safe to stop. And that’s something that’s currently being tested in clinical trials, both in the US, as well as abroad.
And so, we have a trial here at Memorial Sloan-Kettering testing patients who have been on Venclexta and get into this MRD-negative state. If they’re able to stop the drug and it’s basically randomizing—or not randomizing people, they’ll be allowed to decide whether they wanna stop or not.
And then following them to compare the patients that stop versus the patients that didn’t stop to see what the difference in terms of relapse rates are, overall survival, whether it is gonna change the outcome of the disease whether you stop or continue on the drug. So, that’s a great question, and it’s currently one that we’re trying to answer as fast as possible.
Andrew Schorr:
Okay. And, Susan, just so we understand this MRD, these are super-sophisticated tests, right, now looking for cancer cells at like I almost think, maybe not the nano level, but, right? And we haven’t had these for a long time.
Dr. Leclair:
Oh, no, they’re relatively new. For those of us who do have different colored hair than what they started out with, once upon a time, it was one CLL, and we had no treatment for it. And now we have multiple versions of CLLs. And we have, oh, maybe, I don’t know, 10 possible different fairly well-known, fairly well-described genetic anomalies. You’ve got different drugs that go along with it.
So, in each one of those, complexity adds confusion at the same time. So, some of our tests are—oh, no, I take that back. All of our tests have limits. I test for something, and my limit is one in a billion. Well, supposing you have one in two billion? I’m going to come up with a negative, not because there’s nothing in there, but that it is there at such a low number, I can’t pick it up.
So, there are times when you have these results, and minimum residual disease is a great phrase for it. All I can tell you is to the limit of my testing, to the limit of every scientific test we have out there, I can’t find a malignant cell of your CLL in there. Does that mean that it’s absolutely not present?
Andrew Schorr:
Right. But we can measure it better than ever before. And it gives us some confidence. And I think patients want to know. But so, that goes to Justin. Justin, you’re at one of the largest cancer centers. There you are in the lab, and you do all sorts of sophisticated testing. But many of our viewers are around the world and they’re not necessarily being treated at a big academic medical center.
So, the question is, what tests are necessary? So, maybe you could help us understand. If you are out there in the hinterland, and you needed to help yourself as the physician, and the patient just kind of understand what’s going on, what’s the basics? So, first, let’s start at diagnosis. What’s the basics to know what’s going on? Do you have to have a bone marrow biopsy? Do you do CBCs? Do you have to do what we call FISH testing mutational status? What’s like the basic?
Dr. Taylor:
Yeah. Thanks. And we definitely can do, as Susan was saying, many, many tests with different sensitivities and specificities, but kind of the gold standard of proving whether adding these tests makes the difference is to do a clinical trial or a prospective trial, I guess, where you measure these things before patients get treatment, and then see which of them makes a difference in the outcome.
And when you add them all into a kind of analysis that includes all of these tests, which ones are important of themselves because some tests are markers, basically, of something else that you can measure. So, that being said, there have been many studies like this to try to see whether we can add in any of these new tests that have been developed in the decade to the kind of gold standard. And many times all of the new tests that we add aren’t able to distinguish that much more than what the basic tests show, so I…
Andrew Schorr:
…okay. So, literally, let’s just tick off some. Bone marrow biopsy; critical to do?
Dr. Taylor:
That’s very controversial. We still do that. I don’t think that it’s critical in making the diagnosis. That could be made from the peripheral blood flow cytometry, which tells you the markers on the surface of the cell, that they’re different than normal B cells. We still do the bone marrow biopsy to get a sense of the stage of the disease, how much CLL there is. But it’s not absolutely required for the diagnosis.
Andrew Schorr:
Oh, okay. And what about so-called FISH testing; is that important?
Dr. Taylor:
I think it’s important, based on what we talked about with the 17p deletion. It can detect that. That’s a big change on the DNA, on the chromosomes, that can be detected by FISH. And, yeah, many of the tests I was referring to before are looking at specific genes. I don’t think that those are necessary. They definitely can give some insight to the treating physician, but.
Andrew Schorr:
Okay. And then the last one is that I always get this backwards—is it IgVH, IvGH—but the mutational status, why is that important?
Dr. Taylor:
Yes, the IgHV mutational status, if I got it right, is important because there’s—basically falls into two camps. You can have unmutated and you can have mutated, and you would think that the mutated would the worse, but it’s actually the unmutated that has the worse outcomes.
And that’s important, because it’s been shown that this unmutated set of IgHV-unmutated CLL may not be the type of patient that you want to give chemotherapy to. They may not respond as well to chemotherapy. That may be something you want to go straight to one of the new agents.
And for the mutated patients, which have a little bit better prognosis, new agents are definitely on the table for them also, but there’s a subset of those patients who, with chemotherapy, a study done at MD Anderson that followed these patients 20 or more years after chemotherapy, a subset of those with IgHV-mutated CLL did not require further treatment. Essentially, we didn’t say that they were cured, but they were as if they were cured. They only got one treatment with chemotherapy and never required anything again.
Andrew Schorr:
Right. Well, okay. Let me raise my hand. I was in the Phase II trial for chemo, fludarabine (Fludara), cyclophosphamide (Cytoxan) and then rituximab (Rituxan) added in 2000, and I had no other treatment after six months of therapy for 17 years.
Now, I had an MRD test along the way, and dear Dr. Wierda at MD Anderson said, “You know,” with the testing they had then and this is several years ago, “You’re not MRD-negative. You’re probably gonna need treatment again. I feel confident you will.” And so, I knew there’d be another shoe drop. But with the chemo, I did get a long remission. Susan, one of the questions we’ve had is, and you’ve heard this before, people get different lab values from different labs.
Dr. Leclair:
Yes.
Andrew Schorr:
Maybe they had it here. So, you’re like in the international organizations. Shouldn’t there be like one standard; if my hematocrit is this, that’s where it is for everybody? I mean, why does it vary?
Dr. Leclair:
Because you do. One of things that is critical here is that you, the patient, have different levels of hydration from the morning when you get up. This makes absolute sense when you think about it. When you roll out of bed in the morning, you’re not really as well hydrated as you might be at 4:00 in the afternoon, or that you’re not as well hydrated after you’ve run for two hours than you were before it.
Since most of the initial blood work that you use, both in diagnosis and in monitoring, is based on volume, if you got diagnosed with a CBC that was drawn at 3:00 in the afternoon, for the name of consistency, could you keep having your blood drawn at 3:00 in the afternoon? Because that will provide us probably a more constant basis of you are hydrated at this level all of the time.
Andrew Schorr:
Right. But you know what—yeah, but I’m not asking just that question. If I go to the same lab and test at the same time and drink water before, but so, we get lab test results, and in the case in San Diego, it has H’s and L’s, highs, lows, out of the normal range, and I got a bunch of them, okay? But what I wanna know is, is that standard of what’s within the normal range the same at every lab? Or if it isn’t, how come?
Dr. Leclair:
Well, in the case of hemoglobin, for example, if you live in Telluride or Vail or Aspen, you’re at a higher level. There’s a lower amount of oxygen in the atmosphere, so you need more hemoglobin to grab the oxygen from your inspired breath and bring it to the tissues. So, pretty much everybody who lives above Mile High Stadium, so to speak, it’s not that anymore, but everyone will remember it, is probably gonna have a higher hemoglobin than somebody who’s at a lower one.
If I’m in the lab and I’m developing a set of reference ranges for the physicians in that area, then if you come bouncing into Vail and have a CBC, you’re still at your California seaside hemoglobin level. To somebody who’s expecting people to have a higher one, you will look as if you have a lower hemoglobin.
Andrew Schorr:
Right. And I’m going to Colorado in a week or so, so, yeah. Okay. I get it. That was a question we had from several people. Now, Justin, I got a question from you. A lot of the people here, a percentage, have been diagnosed with SLL, not CLL, but we understand they’re basically treated the same. So, help us understand the difference. But what they want to know is should their testing be different?
Dr. Taylor:
Yeah, that’s a great question. We do think of them as the same disease. It’s just the manifestation. In CLL, the abnormal B cells are mostly circulating in the blood, leading to abnormal blood tests with high lymphocyte count.
Whereas in SLL, or small lymphocytic lymphoma, a name that was given because primarily, the abnormal lymphocytes are in the lymph nodes and they don’t circulate in the blood, so patients with SLL would be detected because they have abnormal lymph node swelling.
They might go to a physician who primarily treats lymphoma, which is another related disorder that presents with abnormally enlarged lymph nodes. And so, they oftentimes are monitored different, treated differently, because the cells are not circulating in the blood, so they can’t be detected as easily through a blood test.
So, in my practice, I use the physical exam and monitor wherever the lymph nodes are through examining them, just physical examination. And you can also do a CAT scan, or a CT scan it might be called as well, to measure throughout the body the places you can’t examine within the thorax and abdomen if there are lymph nodes there also.
Andrew Schorr:
Okay. So, the cells are not floating around, so it’s a little different as far as monitoring goes. Okay. So, let’s get to monitoring. Justin, I’ll ask you this, too. So, people wonder, okay, if I’m in remission, how often do I need to be monitored? So, you’re doing the physical exam. My doctor, Dr. Kipps, feels for lymph nodes. He digs under my armpits. He does a lot of stuff.
And that part’s not fun. But and I get these regular blood tests monthly, which are just zapped to them when I get my immunoglobulin, so they’re keeping a watch on me. And I should mention that I have another condition, too, myelofibrosis. So, I got two doctors watching me pretty carefully. But, basically, I don’t see them very often. So, related to testing, is that really an individual thing with your physician as far as just like CBCs, Justin?
Dr. Taylor:
Yeah. To me it’s dependent on each patient, and, as Susan mentioned, the trend of the blood counts, and what treatment you got, how long ago that was. In a general set of rules, the sooner it is after treatment, you might be monitoring it more closely. And then as time progresses, everything’s been looking okay, the time can be spread out, again, based on the individual patient. If there’s continuing, ongoing reason to watch some specific lab test then, as you mentioned, it might be done every so often.
I would say unless there’s something particularly that you’re keeping an eye on, such as you immunoglobulins, you probably don’t need it once a month; every three months is generally acceptable, if everything looks normal, there’s nothing. But in your case, you’re getting these IVIg infusions, and so, they’re testing the levels to make sure you need them every month. And so, it comes down to each individual patient.
Andrew Schorr:
Susan, so, we mentioned this a couple of times, IVIg. And some of our patients who are on this program get it, too. So, what is immunoglobulin, or what are Igs? What is this stuff?
Dr. Leclair:
Immunoglobulins are essentially proteins. They can be transport proteins. You eat a steak, your body absorbs the iron, and it needs to get put on a transporter, so that it can be moved around. So, there’s transport proteins. There are modifying proteins that control how fast or how slow something’s gonna happen.
But the ones you are interested are the immunoglobulins that are antibodies. Now we all know about antibodies because there’s certainly been enough argument across this country in the last few years about antibodies in terms of getting immunizations for children against measles and mumps and other childhood disorders, whether or not it’s Zika, and all the rest.
You have in you, over time, built up a body of antibodies, a collection, an encyclopedia of antibodies that remember that you had that disease 22 years ago. And while you’re not actually making a whole lot of those antibodies, you’re making enough of those antibodies to make sure you’re never gonna get it again.
What happens with CLL folks is that they don’t make either functional antibodies, or they don’t make enough, which means that you at your age might have had an immunization for mumps a long time ago. My guess is you don’t want to have mumps right now. So, we should give you some pre-informed, pre-manufactured antibodies against mumps that will help whatever cells that are in your body that are trying to make mumps antibody to give you enough mumps antibodies so that you never get mumps again.
So, this a procedure that is giving you this infusion of antibodies, is to keep your system at a place where it won’t get sick when you’re in a subway and someone sneezes, when you’re in a restaurant and someone coughs at you, when you find yourself somewhere with a friend who says, “Gee, I hope you don’t mind, but I’m still getting over X.” So, it’s protective for you.
Andrew Schorr:
Okay. And Dr. Kipps here in San Diego says, “Andrew, if you want to travel,” and that’s true, and I like to travel, and we’ve seen many of our CLL friends when we do, he said, “You gotta have the IVIg infusions.”
Andrew Schorr:
Justin, just so we understand, what about—she mentioned immunizations. First of all, where does immunoglobulin come from? My understanding is it’s made from somebody else’s blood. I’m getting like a blood product, hopefully, squeaky clean in that, and I’m getting some immune benefit from that. Is that the idea?
Dr. Taylor:
Yeah, that’s correct. So, the antibodies come from B cells, and that’s why CLL is a disease of the B cells. And so, that’s why they’re, as Susan mentioned, they’re not forming the proper antibodies. So, we can get these healthy antibodies from donors, and it’s usually a pool of those antibodies to get enough to give you that boost.
And I just wanted to mention that not every patient with CLL needs these. You can measure the immunoglobulin levels in the body, and if they’re normal, you may not need the extra boost, especially if you’re early CLL and watching and waiting. And, again, and if patients are getting recurrent infections, that’s another reason that they might need transfusion.
Andrew Schorr:
Right. Yeah, and I’ll mention, to be clear in my case. So, I went 17-year remission, folks. I did get some sinus infections. Usually, if I got a cold, I got sinus infections, took antibiotics, quicker than people who don’t have CLL, of course, and it knocked it out, okay.
What we noticed is, after I had retreatment for CLL with a monoclonal antibody, obinutuzumab or Gazyva, with steroids in my case, about almost two years ago I was getting more often infections. The CLL was controlled, but, like Susan just said, my immune system was inept and it needed some help. And so, Dr. Kipps decided I needed IVIg. But that’s a personal thing with you and your doctor. You may be monitoring how frequently, just what Justin just said, how often you’re getting infections, because it’s certainly not for everybody.
Okay. So, let’s talk. I wanna understand something, Justin. CLL can change over time. So, we mentioned the 17p deletion, or people hear this other alphabet soup, 13q, and all these different things, or trisomy, and all these things. So, the way you start out, is that the way you may be years down the road? And if not, how come?
Dr. Taylor:
Yeah. For some reason, CLL can change. A term you might read about is it’s called clonal evolution. It sounds like “Star Wars” with the clones, but you can basically have the CLL that you started with, it can acquire other mutations, or other abnormalities that you’ve listed there over time, so, even untreated CLL, does change over time. We don’t really understand fully why that is. We know, in general, cancers do that, so CLL seems to be at the faster rate of that ability to change the genetics.
And so, I think the CLL you end up with might not be the same as you started with. And so, this comes to another question that was asked of when to do this testing for 17p IgHV. You often hear the argument that you don’t need those until you’re gonna start treatment because if you get them at diagnosis, and then you’re gonna not start treatment right away, they may change over time, and you wanna reevaluate those at the time of treatment.
So, that is why some patients might not have all the testing done at the time of diagnosis. Not every doctor feels that way, so some patients do get all the tests run at diagnosis, and then again when it’s time for treatment based on the progression of the disease and symptoms. Then often we repeat those just because there’s the possibility that within that time frame, whether it’s a year or several years, that these markers can change.
Andrew Schorr:
Susan, you and I have been around this a long time, and you remember one of the really wonderful patient advocates years ago, Granny Barb Lackritz. Barbara Lackritz. We called her Granny Barb. And one of the words she told us Esther and me, years ago when I was diagnosed, was, “Chill out.”
So, have this array of tests now. And there will be some of our viewers who say, “Okay, I want this test, and I want this test, and I want this test, and I want this test.” And, “Oh, my God, this has moved a little.” And, “Do I need to be retested?” What you tell people to kind of take a deep breath, even though you have this array of testing now?
Dr. Leclair:
I tell them to take a deep breath and to slow down. This is not a disease that is going to “harm you.” That may be in quotations. This is not a disease that will harm you today or tomorrow or even in a year. This is a disease that will allow you to think it through. Well, not necessarily slowly, but deliberately. What you wanna do on these tests is not say, “I want every single one of them.” Because then you’ll get a lot of information you can’t interpret. What you want is, “Let’s do one test at a time.” The results of that test will lead you to the next test.
For example, the CBC gives you a very high white count, and it looks like it’s all lymphocytes. Okay, what do you do next? Well, the next logical question is: Who are these lymphocytes? What are they doing? So, that’s when you do the flow cytometry, and you find the answer of who are they at a gross level, at a fairly simple level. Oh, they’re B cells, or maybe they’re T cells. And in that answer then provides you with the next thing you want to do.
So, instead of ordering them all like eating and taking every single bite out of a huge buffet, you might wanna just wait and follow the detective story as it goes along. And what that will allow you to do is, well, these were my answers in September. Well, these are my answers plus a new one in November. Oh, well, these are my answers in September and November, and now in February. And so, you begin to develop a story. You begin to know your cells. Your physician begins to know your cells.
You can say things like, “Oh, well, in January, I had a cold.” All right. Let’s about then how that cold might have affected the results in January. You already know what the results were in September and November. Let’s look at this in context. You have the time. Use it.
Andrew Schorr:
Right. Now, Justin, we’re talking so much about testing, but you referred to physical exam. So, I think we have to be fair and say you guys look at the complete picture. Like, for instance, is my spleen enlarged? Do I have night sweats?
Do I have new lymph nodes? How big are they? Where are they? Right? Am I getting a lot of infections? Right? So, you gotta look at the whole picture, right? It’s not just the numbers. Correct?
Dr. Leclair:
Absolutely.
Dr. Taylor:
That’s right. Absolutely. Yeah, it’s personalized medicine before that term came to mean doing genomics. It’s every person is different; every situation is different. As Susan mentioned, situational things can happen with infections that change the numbers, and it’s important that – We’re not gonna be able to guess that, so discussing with the patient, hearing the history, taking the time to do the exam, and then, again, putting that into the context and the historical context with that patient.
So, that’s why the patient-doctor relationship is very important. Of course, it’s always recommended, if you want a second opinion, to hear from another doctor or someone that specifically does CLL. But just having your physician that’s known you for a long time is very valuable, as well.
Andrew Schorr:
Let me put in a plug for second opinions for a second. So, Justin’s at one of our premier cancer centers, Memorial Sloan-Kettering. There’re a few of them in New York, where he is. There may be one this way down the interstate from you in New York, or in London, wherever you may be.
And I would say, with a long-term illness, it gave me confidence to check in with an academic medical center. And I actually had teamwork, when I was in a clinical trial, between a local cancer center and a university cancer center.
And I got those doctors talking. That gave me confidence. And when I needed treatment, actually, and ultimately in a trial, they worked together.
So, one of the questions came in and said, “Well, when should I check in with a CLL subspecialist like Dr. Taylor is, even in the lab?” Well, along the way. But as Susan said, “The house is not burning down today.” Okay?
Now, Justin, you’re in the lab there. I have a question for you. So, I have three kids. And one of them, and some people know, are Ruthie, are the producer of this program. And so, we wonder, when you talk about genomics, is there some test we should do to see if my children are at risk for CLL? And should we do that routinely, like you might do in some other more hereditary conditions, when we really don’t know, is there a real hereditary connection in CLL?
Dr. Taylor:
Yeah. We talk about the genetic tests, or the genomic mutations, and that always invokes something hereditary in the genes. But when we actually do these tests here at Sloan-Kettering and other places, we will take the CLL cells, take the DNA from those, and we also get a sample of normal tissue. So, often it’s a swab of the side of the cheek, a swish of saliva, sometimes fingernail DNA, something that we can get that we don’t think has any CLL in it.
And then we sequence them both, and we’re comparing the CLL cells to the normal cells to try to detect the mutations that occurred in the CLL that make them different than the normal cells. So, all of these mutations that we’re talking about are something that happened in the CLL cells sometime during your life. And we’re finding out now that these could have been there, these mutations could have been there for years before they finally manifest this CLL. But they’re not something you were born with. They’re not in the cells of your body or the cells that are passed down to your children. There are very rare cases of heredity CLL, but my understanding is they’re exceedingly rare. I haven’t come across them, but they’re reported in the literature. So, if there’s a very, very strong family history of cancer between generations, a bunch of siblings have a cancer, then that might be a time to consider hereditary genetic testing. Otherwise, CLL is typically thought to arise in these cells along your lifespan. You’re not born with them. They’re mutations that are occurring as you age.
Andrew Schorr:
Okay. So, I’m not recommending my kids get some tests. And also, I’d say, and Susan knows this so well, and Justin, as you’ve gone through your training and graduated to be in the lab and seeing patients, everything’s changed. Everything has changed during my time. And so, if God forbid, one of my family members developed CLL years down the road, it’s gonna be different from what it is now. It’s gonna be different.
So, Susan, just so we understand, go back to something that we talked about, about clonal evolution, okay? And the CLL kinda changing, taking the winding road. Is it the idea that the cancer cell is kind of trying to figure out a way around the medicines, and just proliferate? It’s like sneaky?
Dr. Leclair:
Oh, they’re definitely sneaky. That’s absolutely correct. There are a number of situations that are involved in here.
We don’t really know which one goes with which disease, or if maybe more than one does. But, yes, I suppose, philosophically, you can think of these cells as wanting to live. And they’re gonna do whatever is necessary for them to live. So, you hit them with a medication that is rituximab, probably one of the better known ones. Rituximab hits a particular compound on the cell. And the loss of it, a lot of times, will cause the cell to be damaged and die.
Well, on the cell, and I’m a little on the smart side, I’m just not gonna make that marker on your cell. Or I’m going to put a hinge on it so that it breaks off, so that there’s minimal damage to me. And so, those kinds of things can and do happen to those cells. There is also the issue that, whether we like it or not, every day we go out and interact with something that’s gonna challenge ourselves or our genes in some way.
Three weeks ago, I went to the dermatologist with my husband, because he’s the one who has problems. We walked into this guy’s office and he said, “I’m taking you first. You have skin cancer.” “Excuse me?” That was a surprise to me. Well, how did that happen? It couldn’t have been because I’ve spent a lot of time outside without a hat on or anything like that, but I am not 22 years old. This took a long time for this to happen to me.
So, that’s a sense of a clonal evolution that occurs with repeated incidents of stress. And we all have that, every single day. Sometimes the only thing that happens is nothing. Sometimes you have to get your nose skinned to get stuff off.
And that’s what happens with these cells, as well. They will adapt because they want to live. We don’t, but they do. It is a matter—a contest to see who wins.
Andrew Schorr:
So, Justin, there you are in the lab. And as we come to the end of our program, I guess we wanna make clear, we talked about the whole picture, not just lab tests. But you’re looking at what could be tomorrow, okay. So, it sounds like there’s a pretty good pipeline of treatments of CLL should you have this clonal evolution, whether it’s 17p or something else, where you are gonna have something, please God, to bop it on its head again. How do you feel about it?
Dr. Taylor:
Yeah, we have good treatments now. We mentioned a few of them. I’ll just list some again. Ibrutinib (Imbruvica), venetoclax, idelalisib (Zydelig), obinutuzumab was mentioned, rituximab was mentioned, chemotherapy was mentioned. And so, we have a lot of tools and armamentarium in our pocket. But despite that, none of these are home runs, as it was put recently. So, we’re still trying to come up with other things and figuring out how to sequence them.
So, if you start off on Ibrutinib and then you can go to venetoclax, is that better? Or should we put the two together up front? And that was recently tested. We’re comparing these things and trying to figure out what’s the best way to give them in combination or sequentially to try to prevent this clonal evolution. And in the meantime, we’re coming up with more things to use in the future should these combinations not work.
Andrew Schorr:
Right. And you are. And I just wanna echo something that really the father of CLL study and treatment, Dr. Kanti Rai, talked to us about years ago, as we saw more of these tools you have come together, and you continue as, he said, to try to figure out how to arrange them.
It’s like arranging furniture in the room. There’s more furniture than ever before and you, Dr. Taylor, and your peers start to figure out how to arrange it, and people in laboratory science, Susan’s students, try to give you data to go along with the physical exam to get the whole picture of where that individual patient is. Did I get it right, Justin?
Dr. Taylor:
Perfect.
Andrew Schorr:
Okay. Susan, thank you so much for your devotion. What I get from you, always, is like what Granny Barb says, “Chill out.” You said, “Take a deep breath.” We’re on a long-term journey with CLL. And thank God we have a greater array of treatments. Are you hopeful for all of us, Susan?
Dr. Leclair:
Oh, I’m very hopeful. I think there will be a time when we will see the last person with CLL, just like we will see the last person with a lot of other ones. Look at yourself, Andrew, it’s the perfect example. Seventeen years ago you said, “Oh, God, what am I gonna do? I have to have therapy.” And you had the only therapy we had, and you got 17 years. And now when this happened, you said, “What am I gonna do?” And I said, “Have another 17 years.”
Andrew Schorr:
Right. Right, right. She did. And Esther and I just got back from Sweden, and we had a great time.
Dr. Leclair:
Oh, I’m sure.
Andrew Schorr:
I am so grateful to the medical community, the pharmaceutical community, the healthcare providers. I wanna thank the Patient Empowerment Network for putting this all together. I wanna thank AbbVie and Pharmacyclics for funding it. They had no control. Justin said what he was gonna say. I said what I was gonna say. Susan said what she was gonna say. Justin Taylor, thank you for being with us from New York in your lab. Go get ‘em, Justin.
Dr. Taylor:
Thank you.
Andrew Schorr:
Cure CLL, okay? Susan, thank you so much. You’re retired, but not really. You’re never retired for us, okay.
Dr. Leclair:
You told me I couldn’t.
Andrew Schorr:
No, you’re not allowed to retire. Okay. In Southern California, for Patient Power, but for the Patient Empowerment Network, I’m Andrew Schorr. Remember, knowledge can be the best medicine of all.
Please remember the opinions expressed on Patient Empowerment Network are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.
