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Session 1: What You Should Know About CLL Treatment, Genetic Testing and Research

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Published on September 25, 2018

Watch the replay of session one of our “Understanding CLL: What You Should Know About Treatment, Genetic Testing and Research” town meeting, as a panel of CLL experts, including Dr. Jonathon Cohen,  Dr. Jean Koff and Dr. Kerry Rogers,  discuss the latest in CLL treatment and research. CLL patient Beatrice Meyers also joins to share about her CLL journey. Watch now to learn more about emerging CLL therapies, disease monitoring and working with your healthcare team to determine the right treatment path for you.

This town meeting was produced in partnership with Winship Cancer Institute of Emory University and sponsored by AbbVie, Inc., Pharmacyclics, LLC and TG Therapeutics. 

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Thank you, Andrew and team, for creating the best information source on the web for CLL.

— John

Partners

Winship Cancer Institute

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Transcript |

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. 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.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. 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.

Jeff Folloder:

Before we introduce our medical panel, we’re gonna talk to this young lady over here. Beatrice Meyer, you’re from Atlanta, Georgia, right?

Beatrice Meyer:          

Correct 

Jeff Folloder:  

And you’re a CLL patient?

Beatrice Meyer:          

Yes, that’s correct.

Jeff Folloder:  

I understand that you were diagnosed about five years ago?

Beatrice Meyer:          

Yes.

Jeff Folloder:  

2013ish. 

Beatrice Meyer:          

Yes. 

Jeff Folloder:  

You’re about 75 years old.

Beatrice Meyer:          

Yes, 30 years after you were diagnosed is my age.

Jeff Folloder:  

Wow! Tell us how you got to the point where you learned that you have CLL. Tell us how your diagnosis came about.

Beatrice Meyer:          

That’s a good question. I’m probably the oldest one in the room, so I was thinking at 75, I’m just getting old. Both of my parents lived to be 93, they were very healthy, and I thought I was just getting old, I can’t do this anymore, I tire on the tennis court, I have swollen glands, but I’m just fighting some sort of infection. So, I went to Emory, and Dr. Cohen took care of me. I had some of the same tests you had, and you all probably had, and that’s how I was diagnosed.

Jeff Folloder:  

It’s never an easy thing to be told you have cancer.

Beatrice Meyer:          

No.

Jeff Folloder:  

How did you deal with that?

Beatrice Meyer:          

Well first of all, like many people, I thought it can’t happen to me; but my sister had had cancer. How did I deal with it? I called my daughter, I talked with her, I Googled a little bit but I’m very careful not to Google a lot, I know, I just feel it’s better if I just keep active and do things. But Dr. Cohen was a big help, he was a very big help he put me in a test trial, a trial.

Jeff Folloder:  

Many times, when we receive our diagnosis that the healthcare practitioner that gives us that diagnosis gives us a caution to not to go speak with Dr. Google. There’s a very good reason why we’re told that, there’s also a very good reason why most of us ignore that, right? See, lots of nodding there. There’s a lot of stuff on the Internet, people have likened it to it’s trying to take a sip of water from a firehose that’s open, wide open. So much information. And things change so fast. Was it overwhelming for you to receive the diagnosis or were you comfortable with just dealing with your doctor? 

Beatrice Meyer:          

I suppose it was overwhelming. I just felt that I would do the best I could, I would take the advice that was offered me, and I would just try to live every day. I do have a fairly strong faith, and I’m very active in different organizations, and that helped me a great deal. But still, on a day-to-day basis when you’re tired, you’re tired.

Jeff Folloder:  

Okay. So, how did you and Dr. Cohen decide what treatment path to go down? You had a bunch of symptoms, what made you decide, with your doctor, this is what I’m going to do?

Beatrice Meyer:          

We did the watch and wait for almost a year, I believe it was, and then he said there was a trail, and the test trial, what are they called? 

Jeff Folloder:  

Clinical trials.

Beatrice Meyer:          

Clinical trial.

Jeff Folloder:  

We’re gonna talk about clinical trials in a little bit, I promise.

Beatrice Meyer:          

My daughter went in with me so I had a supporter. I had a blue dot with me, and we talked about the various options of which I believe there were three, and we decided. Of course, when you take these, when you think there’s going to be one, you’re definitely not assured of being in the one you want, or even of being in a test trial. And there was one we really wanted to be in, and, fortunately, I was very fortunate to get in that, it was Ibrutinib, and it was an oral chemotherapy.

Jeff Folloder:  

Mm-hmm. And you look great. 

Beatrice Meyer:          

Well, thank you.

Jeff Folloder:  

How do you feel?

Beatrice Meyer:          

Most days I feel great, I play tennis several times a week, I’m active in my church, and very active with the AAUW, we have our huge book sale coming up, I price all the vintage children’s and all the sports books. I do a few other things too, so most days I feel great.

Jeff Folloder:  

So, would you say that your quality of life is eh, good, great?

Beatrice Meyer:          

I think for 80 it’s great, I really don’t know.

Jeff Folloder:  

Outstanding! You and I were speaking before this event started just to try to figure out where we stood in relationship to each other, and we were talking about being tired all the time. And we kind of aligned on the concept of when you have CLL you’re going to be tired. You get to choose what to do with your energy each and every day. What you do with your energy is what? You lead a great life, right? 

Beatrice Meyer:          

I try to, yes. 

Jeff Folloder:  

Are there any things that you can’t do? 

Beatrice Meyer:          

Well, yes there are a lot of things I can’t do. I feel I can’t ride a bicycle anymore, I’m just not as stable as I used to be steady even though I do play tennis, and I do fairly well. But sure, and there are other things, I don’t really think about them.

Jeff Folloder:  

You have a bunch of people here in the crowd, you have a bunch of people online, you seem to be smiling a lot, you see to have done well with the CLL diagnosis.

Beatrice Meyer:          

Nervous.

Jeff Folloder:  

There’s no reason to be nervous, we’re just chatting here. What advice would you give these folks? If you could tell them one or two or three things to help them lead a better life, what would it be from the patient’s perspective? 

Beatrice Meyer:          

I think surround yourselves with people who want to move on in life. Find a passion, something you just love and do it; you can either do it or not do it. And just live every day; we have a choice, we can get up and even if we’re feeling pretty lousy we can get going. It’s hard for me in the morning, I think, because of my age, and a bit of arthritis to just get out and walk. But once I’m two, or three, or four minutes into walking it’s so much easier, things just start to flow and move together. I don’t know if that’s what you’re looking for.

Jeff Folloder:  

I think that’s very much part of it, it seems counterintuitive to most of the people in the room and most of the people online, we’re tired all the time, go exercise, that just doesn’t connect. Wait a minute now, I’m dragging right now and you want me to go walk two or three miles, and the answer is what?

Beatrice Meyer:          

If you can, do it. Yes.

Jeff Folloder:  

I ignored my exercise regimen, I had a little medical issue back in December where I had to get, you play tennis, I had a tennis elbow issue and I don’t even play tennis. Right? So, I used that as an excuse to not to powerwalk, because I couldn’t swing my arm for a while. And then after I was all completely healed I wasn’t back to powerwalking, I was back to eating very well, and sitting on the couch a lot. And I gained a bunch of weight while I was in the process of relapsing. Well, I have officially relapsed, and guess what? I’m powerwalking every morning again, I’m doing it again. I love seeing your smile, I love seeing you nod up and down, we both agreed you get to choose what to do with your energy.

You’re going to be tired, might as well have accomplished something, right? Is that something that most people can relate to? Not everybody can get out and walk 10, 15 miles or ever four-and-a-half, or even one, but we can all get up and do something and move around. Beatrice, thank you for chatting with us for a little bit, it’s wonderful to have a patient up here. We’re gonna introduce our patient panel, but first help you…

Beatrice Meyer:          

…could I say just one more thing?

Jeff Folloder:  

Sure!

Beatrice Meyer:          

And that is, even though it’s important to be so positive we must listen to our bodies, and there are times when we’re exhausted and you probably found this to be true, and I’m sorry to go on like this, we just have to listen and sometimes just sit on the sofa and just say okay you’re tired today, just sit. And recognize the fact I don’t have to feel guilty if I just sit and read, or if I put something on Netflix; I think that’s important. Excuse me for going on about that.

Jeff Folloder:  

Oh, no. No. That is great advice because a lot of us, especially the gentlemen in the room have a tendency to discount what’s going on and discount the symptoms that we have, so that is excellent advice. Pay attention to what’s going on in your body, acknowledge it, don’t feel guilty about it and let your doctor know about it, right?

Beatrice Meyer:          

Correct. Yes. Thank you.

Jeff Folloder:  

Let’s get you down the stairs.

Beatrice Meyer:          

Thank you.

Jeff Folloder:  

Let’s have all of our medical staff move over here.

Okay, while they’re getting situated, in the introduction I mentioned the diagnostic procedure known as a bone marrow biopsy. If you have had one bone marrow biopsy, please raise your hand. Okay, that’s a bunch of you, put your hands down. If you’ve had two, raise your hand. Okay. And this is to make you guys feel bad, if you’ve had three, raise your hands. Four? Okay, I can raise my hand, I’ve had seven. Bone marrow biopsy is one of the most medieval procedures that I can think of short of phlebotomy. I said that carefully.

Back in ancient times, they really do that bloodletting thing with leeches, and in certain forms of blood cancers alleviating the blood supply is still part of the routine, so we’ve got bloodletting and jamming corkscrews in my hip. I want you to keep that in the back, of your brain for a second because I’m gonna ask you why. Now, here on the panel we have Dr. Jonathan Cohen, we have Dr. Jean Koff, we have Dr. Kerry Rogers, and physician assistant Mona Shums. I’m gonna ask each of you to introduce yourself, tell us a little bit about what you do, where you do it and why CLL is the focus of your practice.

Dr. Cohen:      

Sure. Good morning everybody. I’m Jonathan Cohen, I first wanna thank all of you for coming this morning, it’s actually a really nice day today in Atlanta and for you to spend a couple hours this morning with us, we appreciate it, and we hope that you get a lot of out of the program. I work here in Atlanta at the Winship Cancer Institute, most or my practice is on our main campus on Clifton Road, but I also go up to our St. Joseph’s campus one day a week. My clinical practice focuses on the management of patients with lymphoma and CLL, that’s pretty much exclusively who I see in practice. I also do some work with bone marrow transplant as well. My research is also focused on lymphoid malignancies, I direct our clinical trials program in lymphoma and CLL at Winship, and that’s how I spend a large part of my day.

Jeff Folloder:  

Your turn! 

Dr. Koff:          

All right. Hi everybody thanks for coming, I’m Jean Koff, I am also a physician and clinical researcher at Emory Winship Cancer Institute. In my clinic I exclusively see patients with lymphoid malignancies and my focus is on B-cell lymphomas and CLL. Dr. Cohen mans our clinical trial lymphoma group, I’m a little more interested in the lab or translational research aspect of B Cell malignancies. And so, I partner with labs at Emory to investigate how abnormal B cells may impact patient outcomes and patient care.

Jeff Folloder:  

Kerry, you are from THE Ohio State University Medical Center, correct?

Dr. Rogers:     

That’s true, so if anyone is a college football fan, I will point out that I am missing some college football to be here today. So, I’m a cancer doctor. 

Jeff Folloder:  

I don’t have her.

Dr. Rogers:     

And I work at the Ohio State University at the James, which is a comprehensive cancer center. I’m a physician and my clinical practice is taking care of people with CLL and also Hairy Cell Leukemia. I do both clinical and laboratory research, but I’m the principle investigator on several really interesting clinical trials in CLL. So, I love talking to people about that. So, clinical trials are not right for everyone, but as long as I’ve been at the Ohio State University I’ve been able to see some of the medications that were first given in clinical trials or were given to people in clinical trials that we had folks at our institution participated become approved like ibrutinib (Imbruvica) and venetoclax (Venclexta), which, the first time I heard of them only had letter number compound names. 

So, I guess one thing that I really enjoy about seeing people with CLL is not only learning about what’s important in their world, and making that work with their CLL, but also knowing that where I work we help improve what I’m able to offer people with CLL.

Jeff Folloder:  

Excellent.

Mona Shums: 

Good morning, my name is Mona Shums, I’m a physician assistant, I work with Dr. Koff and Dr. Cohen at Emory Winship Cancer Institute. I take care of patients on the inpatient side. So, I manage patients coming in for chemotherapy or emergent situations when they come into the hospital.

Jeff Folloder:  

Excellent! So, we have a great panel here for you. And yes, we realize it’s not Ohio State University, it’s THE Ohio State University. Thank you for giving up your football this weekend or whatever other activities you may have planned, again it is a beautiful day out here, so we really do appreciate it. If any of you want to know more about exactly what CLL is, I encourage you to hit our website, patientpower.info/cll, under the heading of Understanding we have lots of information that can help you understand what CLL is. Today, our focus is going to be what we do about CLL. 

Now, I mentioned the dreaded W’s, watch and wait, which most of you seem to be familiar with. We’re gonna go down the line. What is watch and wait and why do we have to do it? Why don’t we treat right away? We’ve got cancer, knock it out! Why not?

Dr. Cohen:      

So, I see several familiar faces in the crowd, but I would imagine that for most of you the first time that you had a discussion with you doctor about your CLL, especially if watching and waiting was an option for you, that may have been one of the actual longer visits that you may have had with your physician. And the reason for that is that for many patients being told that you have a diagnosis of leukemia or any type of cancer, the immediate next thought is, okay I have this cancer what are we gonna do about it? And for many of own patients when I have a discussion with them about potentially not diving right into therapy, the look I get back is typically one of disbelief and concern.

And so, then I often will take some time to really talk about why is it that we think that watchful waiting is appropriate in a particular case. And some of that goes back to what CLL is and what we can expect for most patients over the course of the time that they have the disease. And despite all of the advances that have been made, in most cases CLL is a chronic disease but one that we are not often successful in eradicating entirely for the remainder of somebody’s life, okay? And so, what I’m thinking about when I see a new patient is not just what are we gonna do to get their white blood cell count back down, or to get their lymph nodes to go away, but what am I expecting for this patient for the remainder of their life, which we hope will be a very long time.

And what we know is that starting therapy early on, although it may make the numbers look better, and may make some of the lymph nodes on the scan go down does not necessarily impact the long-term outcome for an individual patient. And what I like to tell people is that especially if you’re feeling well and not having symptoms, that really all we can do in that situation by treating you is make you feel worse, right? Because any treatment that we do there is a likelihood of some sort of side effects, there’s the hassle of having to come in for the treatment if you’re getting a treatment in the infusion center. There’s the hassle of having to remember to take your treatment every day if you’re on an oral therapy.

There are costs, and so it’s not necessarily a “free lunch” to go on therapy; and so that’s why I often try to talk with each individual patient about what’s going on in their life, what symptoms they have, and whether or not offering them treatment right away is going to impact either their long-term outcome or make them feel better. And in many cases if somebody’s not having a lot of symptoms and they’re doing what they wanna do, the best choice is to observe those patients closely.

Jeff Folloder:  

Dr. Koff, when should a patient see a CLL specialist? We talk a lot on Patient Power about a hematologist might give you some good advice but you should get a second when, why, how. Why is it important? 

Dr. Koff:          

So, I personally believe that almost anybody with a new diagnosis of any hematologic malignancy should, after consulting with their hematologist or their oncologist, should consider a second opinion; just because you get a wealth of information that you may not get from your hematologist. You get a different perspective, which is always good, even if they agree with your hematologist management, it’s often helpful and confidence building to know that your hematologist is acting in the same way that your CLL specialist might, or lymphoid malignancy specialist might. I think often, and we have a lot of consults from community oncologists and community practitioners who will call us before they even send us a patient and say I just wanna make sure that I’m doing the right thing here.

And so we often, before we even see the patient, are helping community oncologists make sure that they’re doing the standard of care and that they’re acting in the best interests of the patient the way we would. From a patient perspective, I think there is never a bad time to seek a second opinion or to refer yourself to see a CLL specialist. I think, the primary time that I would consider definitely seeing a CLL specialist would be if and when you’re discussing treatment decisions with your hematologist. Because, one, as some patients, I’m sure, have experienced, as you experienced, your hematologist may want to start treatment, but the CLL specialist may, instead, advocate the watch-and-wait approach; and that’s a huge life-changing bifurcation.

Alternatively, maybe you do meet criteria for treatment as per standard guidelines, or per our expertise, and there may be more options that your general hematologist is unaware of. Or that at a tertiary center or at a comprehensive cancer center, there are clinical trials that are alternatives that you may be a very good candidate for. And so, I think at diagnosis or any time during the watch-and-wait period is a good time, but it’s especially important when you’re considering starting treatment, to talk to a CLL specialist. 

Jeff Folloder:  

I will ask one redirect question, because I’ve been watching too much CSI and all that stuff, it’s a question I think a lot of people in the room and online have, should I worry about hurting my doctor’s feelings about asking for a second opinion. 

Dr. Koff:          

No. In a word.

Jeff Folloder:  

You’re not gonna be offended? 

Dr. Koff:          

No, I think most doctors want to do the best for their patients, and if that involves getting the opinion of someone who is an expert in that disease, and that helps the patient come to the best outcome for them, I have almost never interacted with a doctor who has sent a patient to me for a second opinion or for whom the patient has self-referred for a second opinion, who has been disappointed that they’re getting an expert opinion. They are glad that we are helping them to take the best care of their patients.

Jeff Folloder:  

Outstanding! Dr. Rogers, what all is going—what are you watching us? What are you watching in us when we’re in watch and wait? What is it that you’re keeping track of, the what and the why? We get to sit around, stand around doing nothing, but you’re doing something, what is that something?

Dr. Rogers:     

That’s a very good question. And I think there’s a group of things we watch for, but it is a little bit different for each person. So, like you mentioned earlier, you gotta tell your doctor what’s going on in your world, but that’s not just what’s going on with maybe a blood test you had your primary care physician did, or what’s going on with your health, which is important; but also, what’s going on in your life. Because we always look at the standard laboratory tests for blood counts, we examine lymph nodes, those kinds of things when you come, and that’s very important because a lot of times I notice that someone’s hemoglobin or platelet count is going down, that might mean that it’s time to do treatment and definitely time to talk about treatment. 

But sometimes, and it’s not a small fraction of the time, people will bring things to me. You know, you were mentioning that you cut back on your powerwalking, I know you had the elbow issue, but if people tell me I can’t play pickleball anymore. I don’t know if any of you have played pickleball, it sounds really exciting, I’m gonna have to try it.

Jeff Folloder:  

No, thank you. 

Dr. Rogers:     

Yeah, well then, I had one gentleman that I think was just not very in tune with what was going on with him, and his wife hauls him in and this poor man was so fatigued he couldn’t get their mail. It wasn’t two miles down the driveway, it was on the porch. I said someone should have come back sooner to talk about how bad that fatigue is; because it wasn’t something that you should rest up for the day and things are better; this was something that was bad. I’ve also had people that come in and say they had to buy new pants, because they lost so much weight. So, some of those things people bring to me and then I always look at the lymph nodes and the laboratory tests and those kinds of things.

So, I think just to summarize the list of things we look at, definitely what’s going on with people in their world and maybe things that are different for them. Because fatigue that’s so bad that it’s really limiting your life and what you do on a regular basis is a reason to do a treatment. Night sweats that aren’t just a little damp but drenching to the point where you have to change your clothes that you’re wearing to bed, your sheets, and maybe even if you have someone in the same bed as you making them wet. That’s pretty bad, I don’t mean once, I mean for a period of time, usually a couple weeks of this going on.

I think that definitely weight loss, not just hey I went on the Atkins diet and lost 10 pounds. But I had someone that was eating at KFC every day and lost 40 pounds, I said that’s not right, so we should do something about this. So, those are the list with the night sweats, weight loss, fatigue, I’m sure I’m missing one on the symptoms side. The other kind of groups are lymph nodes and ones that are either increasing quickly to the point where you think they’re gonna interfere with activities or things you like to do soon. Sometimes people get a CT scan for some other reason, not because of their CLL, and there are lymph nodes that look like they might cause problems with an internal organ.

I took care of one man who had some in his pelvis that were blocking his urinary flow, so that was really important. So sometimes you find the lymph nodes cause problems. And then blood work’s the last piece. So, if the CLL has gotten to the point where it’s impairing the bone marrow from making healthy blood cells to support the hemoglobin, which is red blood cells, or the platelets which are the blood clotting cells, that would be a reason to start treatment. Everyone always asks me oh, my white count hit X number, should we do something? I’m panicked! They say their white count is 30, I’m saying yes that’s high but I take care of some people that are 300 and it’s actually completely fine.

Then, usually, people reframe what might actually be a bad problem for them for CLL. So, white blood cell count matters, but there’s not usually just one number where you say you have to do something. It matters how quickly the white blood cell count is increasing, those types of things. So, each person’s an individual so it’s a grouping of that. 

Jeff Folloder:  

Kerry, if you’ll allow me, I want to dial back just a moment and go a little bit deeper into a term you used a couple of times.

Dr. Rogers:     

Yeah.

Jeff Folloder:  

That term being fatigue.

Dr. Rogers:     

Yeah.

Jeff Folloder:  

Anyone here in this room experience fatigue, raise your hand. Okay, pretty much everybody here. We’re not talking about just needing a nap, are we? What is fatigue? What is CLL-related fatigue? Let’s put a label on this.

Dr. Rogers:     

Yeah, so, fatigue is actually one of the most difficult things to talk to people about, because it’s really hard to know, it’s complex. A fatigue that I think would be problematic, or something that needs to be addressed with the CLL treatment is fatigue that’s really limiting someone’s activities on a routine or ongoing basis. But I just wanna add here, because this is such an important issue for people, is that not all fatigue in people living with CLL is from the CLL. I’ve actually diagnosed a couple people with sleep apnea that had CLL, and then they got the sleep apnea treated and felt very much better. So, treating the CLL would not have taken care of that person’s fatigue, they also had this other problem.

And one of my colleagues diagnosed someone’s sleep apnea, and it turns out his wife had it too, so now they have his and her CPAP machines, they’re doing really well. So, it’s one of those things where CLL definitely can cause fatigue, it’s sometimes hard to know what else is causing it too, because there’s other medical problems like sleep apnea that can do it. Then also, that’s why it’s so key to know what’s going on in people’s whole world and not just with their blood work. Because to figure out what it is that’s making people fatigued is sometimes difficult, and a lot of times people will tell me, well, I’m very tired, yes, but also, I just went on a cruise around the Mediterranean, and this, and that, and the other thing, it’s not my CLL. I say okay that’s fine.

The things that I know are a hallmark of CLL-related fatigue are really stuff that limits the activities where you can’t find something else that’s causing it. And I’ve seen a few people that just had fatigue to the point where they weren’t functional and they didn’t actually have too many other of those markers I discussed with the lab work and the lymph nodes, but this person took a CLL treatment and is now back to her life. Maybe still has some fatigue but is ecstatic to be back to doing what she wants to do. So, I don’t know if that’s helpful, because it’s such a complex topic.

Jeff Folloder:  

I think it is.

Dr. Rogers:     

It’s kind of like a pool of things that go into that fatigue, and CLL can be a big piece or a smaller piece for each person.

Jeff Folloder:  

You have something to add? 

Dr. Cohen:      

No, I was just going to—I completely agree with everything that Kerry is saying, I find that for most of my patients that are in a watch-and-wait program, that’s probably what we spend the majority of our time discussing is fatigue. And the reason is that, fortunately, we have very effective therapies for CLL that can make the numbers look better. But, and I counsel patients that just because you may have some fatigue and we may treat you, your numbers may look better, and you still may be fatigued. And so, I think Kerry’s exactly right that you really have to think about everything that’s going on with that patient.

There can be other things going on, sometimes too, like depression or anxiety can sometimes manifest as fatigue, other disorders. And then as Kerry as mentioned what people experience as fatigue is different for every individual patient. So, somebody may be working a fulltime job but they notice that they’re having to take, they’ve never taken a day off work in their life, and they had to take off some days of work in the last month or so. And even though they’re functioning normally on many days they’re starting to have more of an impact on their life. And the last thing I would point out as Kerry mentioned is that it doesn’t always correspond with what we’re seeing in the blood work or on scans or an exam.

Jeff Folloder:  

Sometimes it’s the fact that you at the entire large pepperoni pizza and just need a nap.

Dr. Cohen:      

Right. It could be. Right. There’s that. So, there could be things like that, but we have some people that have, we have a limited burden of disease objectively that are very fatigued; and other people who have a white blood cell count of 300,000 and lymph nodes in a number of places that we can feel that have almost no symptoms. So, it really is an individual discussion. 

Jeff Folloder:  

I haven’t forgotten about you Mona. I promise. So, we’re doing all this wonderful watch and wait, or watch and worry as the patients call it. And you guys are monitoring all this stuff, what testing should we, as patients and caregivers, be discussing with our CLL team? What kind of diagnostics need to be done and why are they important?

Dr. Rogers:     

I mean, I think it’s important to obviously have a close relationship with your physician because one, you listen to your own body to know when things start changing and when you should be able to contact your physician and say something is different, and then that prompts them to maybe delve a little bit further into what are we missing? Do we need to do things outside of the routine diagnostic stuff that we’re doing to see is there a progression of disease, or do we then now need to start treatment? And then other things like side effects increase your chance of infection; and so that’s another component where if they start developing recurrent infections that don’t seem to be getting better then that could be indicative of something else going on.

Jeff Folloder:  

So, we’re doing the standard blood test, what did you call it? The CBC with a differential? Or something like that? Which pretty much everyone in here has probably had. But there are other tests with fancy acronyms, there’s the FISH test, and the flow test, and all these, and the bone marrow biopsy. Do we need to be discussing these with our team? And when is it appropriate to have a FISH test? When is it appropriate to do the flow test? When is it appropriate to have you stick the corkscrew in our hip bone?

Dr. Rogers:     

Yeah, I think initially the initial diagnostic workup is pretty comprehensive; important to have a baseline, to know what your baseline is.

Jeff Folloder:  

So, what does a FISH test tell us?

Dr. Rogers:     

So, important things like what makes you high-risk? When would you consider starting treatment versus doing the watching and waiting, or watching and worrying? So, looking at high-risk markers, cytogenetics, genetic disorders that would probably have your physician initiate treatment sooner rather than later, or vice versa. You are low risk, and that you could do more watching and waiting, as opposed to initiating treatment.

Dr. Koff:          

Can I add something? 

Jeff Folloder:  

Absolutely!

Dr. Koff:          

Yeah, so first of all it’s never a bad time to discuss these things with your doctor, really just even if it’s not the right moment to do these things it’s always a good moment to talk about these things if they’re on your mind. So, I think the discussion of the them can be definitely like you said, the first comprehensive visit even if you’re on observation and aren’t getting a treatment. And then any other visit that you think of them, right? So, maybe you just came here and you’re saying you’re really fired up to talk about these tests now with my doctor.

When to do them is a little bit different. So, some of those FISH testing, they do look for markers, which I think we’re gonna talk about in more detail a little later, so I don’t wanna spoil the whole surprise. But they do help you know how long you can expect to be in watch and wait, and it’s an average, so it’s not everybody. So, it can say hey is it probably gonna be like two years, or closer to 10 years before you have to do something? Now, each person is an individual but it helps give you a little idea how long before you develop those things I was things I was talking about potentially.

And then the FISH panel testing and something called IGHV mutation status helps us pick, and we can explain those later, so don’t think I’m not gonna talk about it more. Those help you pick which treatment might be best for you, in fact, as a CLL specialist I have a lot of trouble helping someone decide what treatment to take when it’s time to do treatment if I don’t have those test results. If you have some time to discuss treatment before you really need it, that’s a good moment to make sure that testing is done so that you know which treatments to talk about. Because it now plays a big role in what you pick as a treatment.

And then a lot of people like having them done when they get diagnosed so that they know what to expect from their CLL in the future. So, it’s not something that has to be done for everyone when they’re diagnosed but some people really want that information. And I’ve had two groups of people when you recommend observation, or watch and wait. One group of people says, okay what are we looking for? When do I come back here? And start worrying about what their fatigue level is and all these other things. And one group of people say, sweet, thank you very much, whenever you wanna see me back is fine, I’m just gonna leave here and go back to do and I’m not gonna think about this again until you say I have to come back here.

So, you’ve got two responses that, and people that you think won’t need treatment for quite some time that are in the excellent, I’m just gonna leave here and put this out of my mind for three months until I come back; probably don’t want those FISH testing and everything at the time they’re diagnosed. People that really are planners and want to know what to expect in the future usually do want that testing. And I don’t know if you guys have other approaches to that.

Dr. Cohen:      

No, I agree. I think the only thing I would add is that, I think there was a comment before about is it okay to get a second opinion and worrying about upsetting your doctor? The other thing I would say is at any time your physician asks you to do a test, ask why are we doing this test, and how is it going to help you take care of me? So, a great example is a bone marrow biopsy. For many years, anybody with a hematologic malignancy, for the most part, as part of the standard evaluation we get a bone marrow biopsy at the time of their diagnosis. 

Jeff Folloder:  

Drop your pants, lay down on the table, this is going to be a little uncomfortable.

Dr. Cohen:      

Right. And what we found over the last several years is that for a number of lymphoid malignancies, including CLL, a bone marrow biopsy may not necessarily be critical at the time of your diagnosis. And so, if you already have a good understanding of what your diagnosis is and your CLL is behaving in a way that we would expect it to behave, you may not need a bone marrow biopsy. Now, when it’s time to talk about treatment, that may be a different discussion, and that’s something we can talk about. But, it’s important to recognize why these tests are being done and how that’s going to help your physician, and don’t be afraid to ask, you’re the one –, Whether it’s just a blood test that can be costly or having to go through a bone marrow biopsy, you’re the one going through it and you wanna make sure that you’re comfortable with the recommendation.

Jeff Folloder:  

As a PA you’re on the front line of interacting with the patients more often than any other part of the healthcare team. What is my role as a patient? What is my duty in communicating with you? What do I need to be telling you as part of my disease progression?

Mona Shums: 

So, very similar to what Dr. Cohen was saying is we want you guys to be involved in your patient care. I think sometimes people feel like they can’t ask questions, or they feel uncomfortable asking questions that they might be questioning you or it might come across disrespectful, and this also goes to caregivers. We want everybody, this is a group effort, we want everybody to be involved, even if you’ve asked the question 10 times, we still want you to ask them if you’re not comfortable with the answer. You’re very much a part of this treatment process, kand so if you don’t have an understanding of what’s going on or why it’s going on, or what we’re doing what we’re doing, we want you to ask because that’s really important in getting better, part of the process.

Jeff Folloder:  

So, what symptoms do you wanna know about? I mean we talked about the icky night sweats.

Mona Shums: 

So, actually when we bring patients into the hospital one of the things that we tell them, whether they’re coming in because they’re sick and there’s an infection, or they’re coming in for chemotherapy, or radiation, or anything really we tell patients tell us what’s going on every day even if you think it’s something small, if it’s something minor it could actually be indicative of something bigger going on. And so, even if you think it’s I don’t need to tell you about this, it happened over night, it’s not a big deal. It can be. So, we always prefer more information than not, because the more information we have that’s how we can help you.

Jeff Folloder:  

Excellent!

Mona Shums: 

There’s really no—I mean it can be any number of things. Just communication.

Jeff Folloder:  

Jean, is it fair to say that anyone with CLL has a compromised immune system?

Dr. Koff:          

I think that’s probably fair to say. I think there’s a spectrum of decreased immunity within patients with CLL. Jonathan mentioned disease burden. I think if your CLL is at the point where you have what we would call a higher disease burden, meaning that you have more of the abnormal cells circulating in your bloodstream, or larger lymph nodes, there’s a higher probability that those cells may be crowding out your normal immune cells, your normal lymphocytes and other immune cells that are less able to do their job of targeting foreign entities such as infections like viruses, bacteria, things like that; and less able to do the job of targeting them and destroying them. 

Now, we’re still doing a lot of research as to how CLL impacts the immune system; and how we can detect what your level of immunity actually is if you have CLL. And one of the ways that we monitor that, because we can intervene and potentially help you is by checking immunoglobulin level. So, your doctor may have checked an IgG level, and often, again, because the CLL kind of crowds out the normal immune cells ability to produce antibodies that target infections, sometimes your IgG level will be low. And what that tells us is that your normal immunity may not be able to function as well and your body may not be able to fight off infections that if your IgG level was normal, that your body would be able to take care of.

And sometimes in that case, if your IgG level is low, we can give you an infusion of IVIG which is pooled immunoglobulin from donors. And that way we give you that antibody back and give your native immune system some tools to fight off possible infections. And so, in my practice I usually check an IgG level in any new CLL patient to me, so any new patient visit. And then also in my review of systems, as Dr. Rogers mentioned, we’re asking about your history of infections, we’re asking about whether or not you have more colds than the average person, whether you’ve been hospitalized with pneumonia In that case I would also have a low threshold to check the IgG to see if maybe there’s an intervention that I can do in giving the IVIG and helping your immune system even if I’m not necessarily treating your CLL directly at that time.

Jeff Folloder:  

What about vaccinations? If we have a compromised immune system, if our immune response isn’t necessarily as good as a healthy, normal person, should we be getting vaccines? Should we be getting the flu shot?

Dr. Koff:          

That’s a great question. I’ve actually been researching that a lot lately, because we have a colleague in our group who’s very interested in that question of is vaccination, does it work in patient with lymphoid malignancies who may have a compromised immune system? An immune system that may not be able to mount the appropriate response to vaccination that gives you immunity to whatever pathogen you’re being immunized against. In addition, a lot of the therapies that we give, such as Ibrutinib, they may target those CLL cells, but they may also take out some innocent bystander immune cells, your normal B cells who are the cells that help to mount that immune response.

There have been a lot of studies recently looking at this very question, especially in the seasonal flu vaccine, because that’s something that you are supposed to get every year. And looking at the immune responses both scientifically, by looking at the immune cells themselves and looking at whether they’re targeted against the flu, but also looking at the rate of flu infections in patients, especially taking ibrutinib, who have gotten the flu vaccine. And we do see some signal that one, if you have a lymphoid malignancy, but two if you’re on a B Cell targeted therapy like ibrutinib, and especially if you’ve gotten chemotherapy in the past that your immune system may not be strong enough to mount the same response that somebody who hasn’t been on those drugs or doesn’t have CLL has.

Does that mean you shouldn’t get a flu vaccine? No. Because we still don’t have anything right now that can even offer the chance of protection. And there are some patients who still mount an immune response and that is very protective and prevents you from getting the flu, or complications from the flu such as secondary infections. And so, I am still recommending all my patients get a flu vaccine, but work is ongoing to really see what the difference is in immune response in patients with CLL and especially patients who are receiving CLL-directed therapy.

Jeff Folloder:  

From what I understand, some doctors who specialize in CLL are now even recommending as far as the flu shot goes, not one shot, but two because of that decreased response to the shot. My doctor told me he wanted me to get a flu shot and then four to six weeks later he wanted me to follow-up and get it again, which I’ve never dealt with before. Of course, all I’m thinking to myself is what a lot of people out there, rightly or wrongly think, if I get two flu shots I’m getting the flu, aren’t I? Flu shots give you the flu, don’t they?

Dr. Koff:          

I talk with my patients about this a lot because it’s a common misconception. There is a small percentage of patients who…

Jeff Folloder:  

…please stand by.

Dr. Koff:          

Thank you. So, I talk with my patients a lot, and there’s a common misconception that the flu vaccine either causes the flu or makes the majority of people feel like crap for days and days after they take the vaccine. And they’ve done a lot of studies on this and this is actually a huge barrier to patients getting the flu shot, because there is this fear that it is going to make you feel very bad for a significant amount of time after you get the flu shot. The first thing I would say it’s that’s a small percentage of people who actually have very a severe reaction to the flu shot.

Jeff Folloder:  

But it’s not the flu. 

Dr. Koff:          

No. No. No. It’s not the flu, it is your body reacting and mounting that immune response to the vaccine, but it is not the flu infection. And let me tell you, the flu infection will be a lot worse. Even if you just get a simple uncomplicated flu, it’s going to be much worse than the reaction that you get to the vaccine. In addition, if you have a cancer like CLL you are at increased risk not just of getting the flu but of getting a secondary infection that rides on the back of the flu and can take over either in your lungs or just overcome your immune system; and you can get a life-threatening pneumonia, or a staph infection, or things like that. And so, the reason that we recommend the flu vaccine is not just to protect you from the flu and a week of feeling icky, it’s to protect you from getting hospitalized with something that can be much worse than the flu.

Jeff Folloder:  

Dr. Cohen, what about the shingles vaccine, as we get older most of us have experienced chicken pox so I understand this nasty little bug is hiding inside of us. I watched a neighbor of mine go through a shingles episode and I was absolutely horrified and all I had to do was watch. I was told for the past eight or nine years, sorry you can’t have the shingles vaccine. Has something changed?

Dr. Cohen:      

Yeah, so shingles is—my dad does not have CLL, but he had shingles, I guess two to three years ago, and still today, from time to time, has discomfort from it. I know there are probably some of you that have had it as well. So, it’s a real problem. And in the best of circumstances it’s very painful and then it resolves. But in the worst of circumstances it can lead to a life-threatening systemic infection. The challenge is that historically the shingles vaccine has been more of what we consider a live virus vaccine which is a problem for patients that have been on treatment or that have impaired immune systems. Even though it’s what we consider and attenuated virus, meaning it’s weakened it still has the potential to actually induce the disease.

One of the exciting things that we’ve seen recently is that there is a newer form of the vaccine that’s been developed that is not live and that is potentially an option for patents that have received treatment. Okay, this is called zoster vaccine (Shingrix), many of you may have heard about it, and many of my patients have asked about it and it’s something we feel a lot more comfortable offering for patients. 

Jeff Folloder:  

Excellent!

Dr. Cohen:      

There are also sometimes oral preventive medications that we can use for patients that are on treatment to try to prevent shingles, but it’s not 100 percent. Anyway, something certainly to talk with your physician about because we do have some options now that we didn’t necessarily have in the past.

Jeff Folloder:  

I’m gonna go back to the other end of the panel. Mona, we’ve been talking about physical issues here, night sweats, fatigue, shingles, the flu and all that. Watch and wait is sort of like all of our introduction to having to deal with emotional and mental aspects of a diagnosis of a chronic cancer. Can you offer our audience, both here an online, any recommendations for getting help with some of the emotional aspects of a diagnosis?

Mona Shums: 

Sure. There are so many resources out there, like you said, Facebook, local communities, we encourage people to meet other people with similar diagnoses, or have been through it or going through it, or have had a family member go through it. We understand that this is not just treating the physical part of the disease, but there is also the emotional part, the psychological toll that it takes not only on the patient but even the family members. I think as clinicians, we actually rely really heavily on caregivers, because when we can’t see the patient we rely on you guys to let us know the patient may underreport what’s going on, because they don’t wanna go through the additional tests.

They don’t wanna be hospitalized, but caregivers also provide us a second pair of eyes to say no there is something different. And so, there are so many support systems out there, there are so many options. Online, within your community, even within the hospital or the cancer institute that you go to, we encourage people to reach out to your physician or your nurse practitioner or PA, because they may be able to tell you what local support systems there are even within the hospital itself.

Dr. Rogers:     

If I could add to that, I think medicine is moving more in the direction of comprehensive care of the patient that extends beyond the physician or beyond even the treating physician. And so, in my own practice I think I’m recognizing more and more that good patient outcomes, whether it’s eradicating your disease, keeping your disease under control, or maintaining a good quality of life doesn’t begin and end with treatment of your disease, or management of your disease. Because this is such a stressful, and sometimes even traumatic event in people’s lives to have the stress of the diagnosis, or anxiety about treatment, I may not be the best person to treat them, because my focus is going to be on managing your cancer.

And for me, that means that I need to be able to recognize and talk with my patients about when they are feeling overwhelmed, or when they’re feeling anxious, or depressed, or lost with their diagnosis or their treatment. And being able to have a conversation with them about what other resources are that I can offer them, which for me, a lot of times means reaching out to one of my colleagues in supportive oncology. And these are nurse practitioners, PAs, MDs, who specialize not in treating your CLL but in treating anything that may be making you feel uncomfortable, or in pain, or anxious, or overwhelmed, or depressed, and taking care of your symptoms and how you’re feeling. 

And so, for any of my patients I have a very low threshold to utilize that aspect of care, because I want my patients to have a good quality of life regardless. And often, that means not just treating their cancer but treating their emotional symptoms and having someone who’s really dedicated to that. So, I lean on supportive oncology a lot.

Jeff Folloder:  

Just to reinforce what you’ve said. Stress and depression are exhausting, and they absolutely can make your symptom load even worse. So, it’s really, really important that you communicate clearly to your team what’s going on. If you’re all stressed out they need to know it, if you’re depressed they need to know it. And most importantly, guys, I’m speaking directly to you here, bring your care partners with you; because when you’re asked the question how’s it going? And you say fine. And your care partner is doing this, we need to get to the root of the matter. I’m not saying it’s just guys that sandbag the doctors but it’s usually guys that sandbag the doctors.

Dr. Cohen:      

I was just going to add that I think, I agree with everything that Jean said and Mona. I think that, at least in my own experience I find that depression and anxiety are probably a bigger challenge in patients with CLL than maybe some of the other patients that we see. And I think that’s because it’s a little bit of a different disease, right? So, if somebody gets diagnosed with breast cancer, for example, and is gonna go through surgery, or maybe gonna go through a course of chemotherapy, often their supporters and their community will rally around them, they’ll help them get through the surgery, they’ll help them, maybe, get through their chemotherapy, and it’s a little bit more of a defined time period.

But for a patient with CLL you may not even be treated for three to four years. There are a lot of things that come into that, so the first is some well-meaning relatives or friends may hear you have cancer but you’re not going to be treated. That certainly isn’t going to lower your stress by hearing that from well-meaning loved ones. And also, the next thing they say is good this person doesn’t necessarily need treatment, so they must be feeling fine, they must be doing well. And we all know that on a daily basis that you’re still living with the disease, you’re thinking about symptoms, worrying about fatigue, and so I think that that’s something that for a lot of my patients that are on observation, even though they’re “disease” may be fine and may not be progressing, they still are struggling with symptoms of the disease including stress and anxiety and depression.

It’s really important to recognize that and to bring that to our attention, and I can assure you that you are not the only one. I’m sure if you took a poll in this room many of you have experienced over the course of time that you’ve had the disease those types of symptoms, and so it’s really important to bring that up, because there are resources to help you.

Jeff Folloder:  

Whole lot to wrap our heads around. I hope each of you are writing down some questions that you’d like to see answered in our Q&A a little bit later. I’m also here to encourage those of you online [email protected] we wanna hear your questions as well. Kerry, I’m gonna start with you. This is the part that’s different for everyone, how do I know when to start treatment?

Dr. Rogers:     

Oh!

Jeff Folloder:  

I’m giving you the easy question.

Dr. Rogers:     

Yeah, right! No, I mean I think you hit the nail on the head when you said it’s different for everyone. In most cases, it’s not even just one thing, but a group of things that make it the right time to start treatment. And one of the things about CLL that is both a good thing and can be a difficult thing is that it’s very uncommon to find out that this person needs treatment and have to do it the very next day. So, normally you get a little time to think about what the best treatment for you might be, and to talk with your doctor about it, and those kinds of things; which is good because you get more time to plan and decide if there’s options, what to do; but also difficult because sometimes you just got to do it and if you delay it too long, you’re just gonna feel sicker and sicker.

I’ve had people say can I just put this off six months? I say that’s not a good plan. You know? Yes, you could put treatment off six months; I don’t think that would work out very well for you as a person. So, it’s really tough because it’s rarely tomorrow. But, I talked about some of the things before about when to start treatment, but I’ve had some people that just had lymph nodes that maybe wouldn’t even bother a different a person, but for them the fact that they had lymph nodes in their neck was really just making their life difficult, so that was a reason, and they didn’t have very much blood disease.

And I’ve had people that are looking at me saying really, I need treatment? Because they didn’t have any lymph nodes that they noticed, they’re feeling great and have never had a better season of golf than they had in their entire life—or are very busy professionally and were just surprised. And you look in their hemoglobin and platelet count are going down, and their white blood cell count is going up, I’m saying these numbers really look like if you don’t do something soon, you’re gonna end up needing blood transfusions or getting really sick from this. They say they trust me, but they didn’t see any of that because they feel great, and they couldn’t find any lymph nodes.

And then, as Jonathan pointed out, you get people that feel terrible from CLL, you’re convinced it’s from CLL and their blood work looks actually really quite good. I mean there is some CLL but everything else is good, there aren’t too many lymph nodes, so it’s really different for every single person, and the decision you make along with your doctor, that’s why you gotta tell your doctor what’s going on in your world, and then they’ll tell you what they’re noticing. You can talk about it back and forth. I also think there’s just this time period that’s difficult when you know you’re gonna need treatment and you don’t have to do it tomorrow, some people try to just keep putting it off to the point of becoming quite ill, then.

And some people, if it’s time say they want to do this tomorrow, and you say we need a week to get your insurance company to agree. There’s that, too. I don’t know if you guys have had that difficulty when you’re talking about hey because of the X things for you as an individual, it’s about time.

Jeff Folloder:  

You know, I like to think about this whole when is it time to do treatment? With all due apologies, I wanted to wear a duster and mirrored sunglasses because this is like the Matrix. Every single component of the CLL diagnosis is different and varies for each patient. Someone with 300,000 for a white blood cell count may be just fine for the next five or six years. And somebody at 15,000 may need treatment next week. Somebody may have a 17p issue and somebody may be trisomy 12. It’s different for each of us so there’s no stock answer that you can give anyone. That’s gotta be difficult.

My question, Jean, is, you know that a patient is moving toward that treatment nexus, what additional tests are you gonna do to confirm that that’s the right course of action and what are those tests gonna tell you?

Dr. Koff:          

So, I would say that even though everybody’s indications for starting treatment may be a little bit different, what I tell my patients is the overarching theme is that if we see that the CLL is causing problems either in how you feel or looking at lab work, or if the CLL is growing quickly either when we look at your lymph nodes on scans or we’re following your white count, if it’s growing quickly enough that we think it might cause problems in the very near future, those are the two overarching principles that I use to start to think that somebody  may need treatment.

And when I start to see either of those two things, either disease that looks like it’s growing quickly, or a patient that has symptoms or evidence on lab work or scans that the CLL is starting to cause problems, then I want to decide which type of treatment would be best for the patient. And one of those aspects that go into my calculation would be lab work and especially looking at the CLL cells themselves. So, if somebody has not already had FISH testing or IGVH mutation testing that is definitely something I would test at the time when I thought treatment might be indicated soon, because those are huge players in your treatment decision. And a big enough decision that it might be the difference between getting IV chemotherapy versus a drug that you take orally maybe indefinitely. 

And so, those are the two most important tests of your CLL that I check beforehand. But then I’m also going to talk with the patient about their preferences in terms of what type of treatment that would be most beneficial to them, or jive the best with their lifestyle, and what they’re looking to get out of treatment. But you can do those tests with peripheral blood, if as long as the patient has circulating CLL cells, those are both tests—well, the IGHV test can be done with sequencing and so that’s easy to do in the peripheral blood. And then as long as you have enough circulating disease you don’t’ have to get a bone marrow biopsy to perform the FISH, you can just do it on peripheral. 

Jeff Folloder:  

I want that in writing. Because I don’t wanna have bone marrow biopsies again. I’m gonna go ahead and move to the next slide. Dr. Cohen, what are common first- and second-line treatment options, and what are your goals with these frontline treatment options?

Dr. Cohen:      

Okay. I’ll try to sum that up in a fairly brief statement.

Jeff Folloder:  

It’s a lot. 

Dr. Cohen:      

Yeah, you could spend, I think, an entire day just thinking about that. So, as Jean mentioned, at the very beginning when a patient is first diagnosed, the main question in my mind is does this patient have CLL? And assuming they do, does this patient need to be treated? And that’s really what I’m thinking about at the very beginning. But as we’ve just been discussing, in most cases patients are going to progress to the point where they need to be treated for a variety of reasons. And in that situation, there are a number of different things that I take into account, some of which are related to the disease and some of which are related to the patient.

So, as Jean pointed out, there are a number of different tests that we can do that can help identify those patients that are maybe going to do best with one particular approach to treatment, or, conversely, who may not respond as well to a particular type of therapy. We use the FISH test, and the mutation test to help us help make those decisions. But the third part of it which is equally important is the patient and their lifestyle and their preferences. So, I have some patients that—just to back up in my mind—there are two main approaches to treatment. There’s IV chemotherapy-based treatment, and then there’s oral therapy.

Now there are new studies and so forth where there may be some combinations, but in general, for most patients you are thinking about, are we going to do an IV chemotherapy approach or an oral treatment? And they both have, taking the CLL out of it, they both have their risks and benefits. So, the IV therapy, typically, is a little bit more aggressive, we administer it in the outpatient setting but it’s no uncommon for patients to end up being admitted to the hospital for infectious complications. It’s not uncommon for patients to require blood and platelet transfusions.

And many patients, depending on the type of IV therapy that we use may end up having to take a considerable time off work, or at least having to cancel some of their plans that they may have. We don’t always allow for patients for example go on exotic vacations if they’re in the middle of their chemotherapy. The benefit is that you are treated for six months, roughly, and then if you’re in remission, then you’re done. And you may be done for six years or longer. And there is some data from MD Anderson that for patients that are in the lowest risk group, that some of our chemotherapy approaches, they have patients that they’ve been following for 10, 12, 15 years, and they’ve never relapsed. And that’s after getting a couple months of treatment.

Conversely, the oral therapies tend to be a little bit easier to take on a day-to-day basis. They tend to have much less of an impact on your daily activity, you can often continue with work, continue with travel, continue with whatever it is that you like to do. So, we heard, for example, my patient who’s still playing tennis actively while on an oral therapy; the downside is though, that at least right now in September of 2018 there is not necessarily a stop date for those treatments. And so, if somebody goes on an oral therapy they are, in a sense, committing to being on therapy indefinitely. Now I never like to say for the rest of your life, because there are things that come up, and there are reasons that people may stop, but there’s not necessarily a specific stopping point. 

Now, I’ve purposefully not gotten too much into the nitty gritty of the specific treatments, I think that… 

Jeff Folloder:  

…because we’re doing that on the next slide.

Dr. Cohen:      

We’re doing that on the next slide? And I think for each individual patient what chemotherapy looks like, and what oral therapy looks like can be a little bit different, and there are a lot of things we take into account. But that’s my general approach.

Jeff Folloder:  

Just a housekeeping note, we are aware that the air conditioner is a bit of a problem right now and the hotel is working on it, so my apologies. We have three letters up here on the screen. I’m gonna ask you to elaborate just a little bit. I mentioned that I experienced MRD Negative as a result of my clinical trial. What is MRD? And why is being MRD-negative a good thing?

Dr. Cohen:      

Is this for me as well?

Jeff Folloder:  

Yes.

Dr. Cohen:      

Okay. So…

Jeff Folloder:  

…and then we’re gonna go down the line if any of you guys have anything to add.

Dr. Cohen:      

So, I guess just to even take a step back, what are we trying to do when we treat a patient with CLL, what is our goal? The first goal especially if somebody’s having symptoms, is to have them feel better. That’s our first measure of success is that if somebody’s having symptoms from lymph nodes, or fatigue or from anemia or whatever it may be, we want them to feel better. That’s what we’re trying to do. But once we’ve accomplished that goal, then we start to really look at more objective measures of response to treatment, and that helps, at least helps me, get a sense for how long is this response going to last, and how well may this patient do over a long period of time?

And there are a number of ways that we can objectively assess response to treatment. And the easiest is to draw your blood and to check your blood counts; so, if you had a low hemoglobin or a low platelet count, we can see those start to recover. If you had an elevated white blood cell count, we can see that start to go down. We can see lymph nodes shrink. So, those are all objective measures of response. And for a long time that was sort of the way that we would assess response to treatment. In recent years, we’ve started to develop newer ways to go beyond that. 

So, yes, your blood counts may be normal, yes, your lymph nodes may be gone; but we know in most cases patient’s disease is going to come back, and we can’t always tell at the time of finishing therapy how long that’s going to be. And so, we have newer approaches to look into that. And what that group of approaches is collectively referred to is MRD, or minimal residual disease. This means disease, so in this case would be CLL that is still present in the body, but that is not detectible by our most common means. And there are a number of different ways to test this. And, depending on the type of therapy that you’ve receive, this may or may not be a critical piece of your case.

So often, for example, with people that receive chemotherapy and that are stopping treatment, MRD is a little bit more of a common goal. Whereas patients that might be on oral therapy where the rate of achieving MRD negativity is not as high, if those patients are tolerating their therapy well and have had a good response, I may not care as much about whether or not they achieve MRD negativity because what we’re going for with that treatment is a little bit different. The last thing I would say is that MRD testing, and I’ll be interested to hear what the others have to say, in CLL is still a little more of—it’s just on the cusp of being used in clinical trials and started to carry forward in clinical practice.

I would say that at least in my own practice if I were to test somebody for MRD and they were still positive, and they had completed chemotherapy, I wouldn’t necessarily immediately think that they needed to go back into treatment. So, if you are having an MRD assessment, or if you end up enrolling in a clinical trial and MRD is part of it, I would make sure that you have a good discussion with your physician about what does this MRD mean for you and what to expect for you moving forward. 

Dr. Koff:          

Can I go now?

Jeff Folloder:  

Everybody wants to jump in the pool here, I can see. 

Dr. Koff:          

So, there’s a couple things that people commonly ask me about MRD that I just wanna say, because I think it’s really important towards understanding it. One was what Jonathan just said, and that it’s not really important to assess in people that aren’t in clinical trials in most cases. So, it’s not something that is routine or needs to be done. So, if you’re taking an oral agent like Ibrutinib that works extremely well even though it doesn’t really cause a lot of MRD negative responses, it’s more of a research question than a regular clinical practice question. A couple things about it. So, it’s minimal residual disease, and you wanna be MRD-negative, meaning there’s no detectible leukemia, but that doesn’t actually mean that there’s no leukemia left in the body, it just means we can’t,,,

Jeff Folloder:  

,,,that’s a mean fact.

Dr. Koff:          

Yes, exactly. It just means that when we looked with whatever test we used, we couldn’t find it in the blood or couldn’t find it in the bone marrow or couldn’t find it in the blood, or the bone marrow. But that doesn’t mean that it’s not in some of the tissues of the body. You know CLL is a blood cancer and can go anywhere the blood goes which is everywhere. It also means that there could be leukemia still in the blood but our tests just aren’t sensitive enough to detect it. I have people that come back that are in clinical trials and ask if they’re cured, is the CLL gone forever? Because they’re MRD-negative, and the answer to that is no, actually we don’t think so it just means that it’s below the detection limit of our testing. Does that make sense?

Jeff Folloder:  

That makes great sense. 

Dr. Koff:          

The other portion of it is the most commonly used test is the flow cytometry test where they take blood, it’s really exciting, they paint antibodies on the white blood cells and fire it in front of a laser to see if there are CLL cells in there. It sounds fun because there are lasers and in reality, it’s like a big machine that…

Jeff Folloder:  

,,,and sharks too.

Dr. Koff:          

Yeah.

Jeff Folloder:  

Sharks with lasers.

Dr. Rogers:     

It’s very fun. 

Dr. Koff:          

But you don’t get to see the lasers, right? Anyway, that’s the most common test. There are now, some research assays, because like I said this test there could still be some leukemia that this test doesn’t pick up, so there are some research assays looking at some sequencing tests to look at a particular genetic change to try to find leukemia cells in even smaller amounts than the regular flow test can pick up. Those are really exciting to researchers but aren’t necessarily important for people that aren’t really into research and that kind of thing. So, some people just don’t wanna know about these things, it’s kind of individual on the patient’s side how invested they are.

After chemo, immune therapies which is like the IV chemotherapy regimens that we were talking about having no detectible leukemia generally improves how long you’ll remain in remission, or how long before you need a treatment again. I think it’s probably going to be true with these new oral targeted agents and these exciting clinical trial combinations of targeted agents. But those are very new, and so we don’t have the 10-year follow-up that we do with IV chemotherapy. So, as Dr. Cohen alluded to, there’s a regimen called FCR, which I’m not gonna talk about in detail but in people who are IGHV-mutated who took FCR some of them still have no detectible leukemia in the blood at 10 years, which is really exciting.

But that’s not something that is necessarily gonna happen with FCR regimen for everyone that undertakes it. So, you also have to be careful what your goals are, what you expect out of treatment before you think about is having no detectable leukemia something that matters to me. Is that?  I’m sure Jean has things too.

Jeff Folloder:  

Excellent. Let’s pull up the next slide here, you used some of those acronyms there, and now is probably a really good time to talk about these frontline treatments. Jean, you start us off, the patient is young, fit and IGHV-mutated. Why is FCR the best choice for that person, or not?

Dr. Rogers:     

So, as Dr. Rogers and Dr. Cohen have both mentioned, with the IGHV mutation we have a lot of evidence spanning now decades that patients who are young, fit, meaning they can, we think they’ll be able to tolerate the chemotherapy well with fewer adverse events than somebody who is older. It can have very long, very durable responses or even remissions with this intensive chemotherapy regimen. 

Jeff Folloder:  

I’m gonna interrupt you for a second. You said long and durable. I’m sure the people online and here wanna know what is long and durable? Is it a year? Two years?

Dr. Rogers:     

So, as has been mentioned this has been longer than one year.

Jeff Folloder:  

Okay.

Dr. Rogers:     

So, the average tends to be around for mutated patients around five to seven years, and so that’s an average. So, there are people who are at both ends of that spectrum. But there’s now more and more data that people with the IGHV that’s mutated, that they can expect to have longer remissions, sometimes 10 years, 12 years, 15 years. And basically, that IGHV mutation acts as a marker for patients who are more likely to have remissions that are on the end of that long spectrum where it’s more than the median time that they need before they need treatment.

Jeff Folloder:  

So, to summarize if you’re mutated, treatment is more likely to give you a durable remission?

Dr. Rogers:     

Treatment with FCR in particular.

Jeff Folloder:  

Got it. So, we have a couple other things going on here. Young and fit but not mutated, things change, now we’re throwing in the ibrutinib which is, I believe everything that ends in ib is an inhibitor, right? Slowly but surely, after eight or nine years I’m starting to figure some of this out. For the whole panel, let’s talk about some of this a little quickly because the next part we’re getting into some of the newer immunotherapies. This is gold standard, correct? This is standard of care for frontline treatment?

Dr. Rogers:     

The FCR?

Jeff Folloder:  

Mm-hmm.

Dr. Koff:          

Yes. And so, Dr. Cohen and I have actually talked about this quite a bit for the patient population who’s young and fit, and their performance status wise we think they would be able to tolerate the intensive chemotherapy. As we do more studies where we test the mutation status, what we found is that especially when compared to patients who are IGHV-mutated, patients we are unmutated tend to have not as good of a response to the FCR chemotherapy. And so, patients who receive that therapy are less likely to have those long, durable remissions or long, durable responses compared to patients who are mutated.

And with the newer kid on the block, ibrutinib, there are a lot of studies ongoing to see whether patients would be better served if they have this unmutated status. And so, it’s less likely that they’re going to get a durable remission with this intensive chemotherapy. Whether it actually might be better both in terms of quality of life, and also in the ability and the likelihood that you’re going to get a good durable response whether it might be better even though we think they could tolerate the chemotherapy that they might actually have a better response and better outcomes with Ibrutinib.

And so, there are a lot of practitioners in CLL who are actually changing their recommendation whereas before we would have said, you’re young, you’re fit we know about your mutation status, but we’re gonna go ahead and give FCR because that’s the category I, the best level of evidence. They’re changing their frontline treatment of these patients and actually started ibrutinib rather than IV chemotherapy.

Jeff Folloder:  

So, truly we are at the edge of personalized medicine. It’s not a one size fits all, it’s not even a two bucket situation, it’s a we’re dialing it in to the exact person. Let’s take a look at the next slide then. We’re talking about MABs and MIBs and IBs, we’ve got chlorambucil (Leukeran), fludarabine (Fludara) and all that, we’ve got chemotherapy agents and immunotherapy agents, what is this giant soup that we’ve got to choose from, Kerry?

Dr. Rogers:     

Yeah, so I think that when you look at standard therapies, I will point out from the previous slide that Ibrutinib is approved by the US FDA as a first treatment for people. And also, we mentioned that FCR is not for everybody so there is some lifestyle choice in there too for people that just don’t want to do FCR even though they might benefit. So, combination therapy is a good approach to eliminate more of the leukemia cells and generally get deeper remissions. This is not the right approach for everybody because as you think about it, you don’t get anything for free, and the more things you throw in the soup the more side effects you’re gonna have.

So, what you’re getting is treatment for the CLL but what you’re giving up is side effects, that kind of thing. So, you’re never gonna get anything that has no side effects, so the more classes of drugs or types of drugs you throw in the more potential for side effects even though you might get deeper remission. So, it’s a balance of those when you’re thinking about treatment for any individual. So, the class of agents on the screen there, is actually the oldest or first class of agents we had for CLL, including the oral alkaloiding agent chlorambucil which is very tolerable but, in many cases, not as effective as these other agents. It’s a pure nucleoside analog therapy, bendamustine which has some properties of both, and then another IV chemotherapy agent called cyclophosphamide (Cytoxan), and all these drugs work by interfering with growing and dividing leukemia cells to kill them off.

I don’t know exactly how to describe it but they kind of work by killing more rapidly dividing cells and they kill the leukemia cells better than they kill healthy cells in the body. But they’re still cell killing agents compared to immune therapies which help your immune system kill the cells, or oral targeted agents where instead of just killing cells they actually are specifically getting into the leukemia cells, binding to something in them and altering their cellular physiology in a way that makes the leukemia cells die. Hopefully that was sort of an explanation.

Jeff Folloder:  

Perfect.

Dr. Rogers:     

This is the cell killing agent’s page. 

Jeff Folloder:  

Now, we’ve got the MABs, and I apologize in advance because the second one listed there is ofatumumab (Arzerra), and you can’t say it without sounding like Arnold Schwarzenegger. You have to do it that way. All these drugs have MAB at the end, and that is short for what?

Dr. Cohen:      

Monoclonal antibodies. 

Jeff Folloder:  

And what are these monoclonal antibodies doing and why is it good for treatment of CLL?

Dr. Cohen:      

Sure. We all have antibodies in our body and they’re part of our immune system, and what the antibodies do is they recognize an antigen or something that isn’t supposed to be there and help the immune system take it out. And so, one of the things that we’ve been able to do over the last 20 years in CLL as well as other lymphoid cancers, is to identify aspects of the CLL that distinguish it maybe from other cells or distinguish it at least from some of the more normal cells and target that using antibodies. So, these are all antibodies that specifically target CD20, for example, which is a markers of B cells.

Now that does sometimes, also, target other B cells that are normal cells so there can still be some side effects, but this is a much more of a targeted therapy that uses the body’s own immune system to either augment the chemotherapy or to take out the cancer by itself. So, it’s a little bit different than what Kerry was describing before with chemotherapy where those are just a little bit more of a blunt instrument that’s designed to take out rapidly dividing cells; these are much more targeted therapies. 

Jeff Folloder:  

Great! We’ll go to the next slide and this one is for you Jean. These are the inhibitor class of drugs that people have most likely heard about ibrutinib and venetoclax how are these drugs working and how does this benefit the CLL treatment regimen?

Dr. Koff:          

So, in the last 15 years we’ve really seen a renaissance of these targeted intracellular agents and a lot of that has come about because we have scientists and researchers who have looked at what makes a CLL cell not die? Why don’t these cells die? Normal B cells do their thing, they grow, if they are matched to a target like an infection they proliferate, or they grow more, and then they die. But these CLL cells have lost that ability to listen to the body about when it’s time to grow, and when it’s time to stop growing, and when it’s time to die.  And so, what we found with lots of good research over the past 20 years or so is that inside these cells there are processes that give them a survival advantage where it either turns on the signal that the cell gets to continue living.

And so, the cell says okay, I’m gonna keep on truckin’, or it turns off signals that tell the cell to die. So, normally B cells have these programs in them that tell them when it’s time to die because otherwise you’d have way too many B cells, which is essentially what happens in CLL is that you have these B cells that proliferate out of control. And so, as we’ve learned more about these pathways and these signals we found that there are Achilles heels within these signaling pathways that we can target with these agents. So, each of these agents are what we call small molecule inhibitors that target these Achilles heels and either turn off the pathways that are—essentially, they turn off the pathways that are keeping the cells alive; whether that’s turning off signals that are survival signals for the cell or by essentially turning on signals that would cause the cell to die.

And so that’s the big picture. But each of these agents targets a different pathway, or a different molecule in those survival or death pathways.

Jeff Folloder:  

So, I mentioned earlier, sort of trying to take a sip of water from a firehose right now. We’ve got three major classes of treatment option. We have traditional chemo, we have monoclonal antibodies, and we have these small molecule inhibitors, and sometimes we pick and choose from the menu. We take some from column A, some from column B, and some from column C. and just to summarize, this is under the heading of personalized medicine because of all of those tests that you’re running we’re learning whether the patient is mutated, or unmutated, if they have a particular chromosomal abnormality that might be a little bit more serious than someone who’s just perking along at a low level of indolence, as it were. But you get to pull some of everything and customize it for most patients, is that fair?

Dr. Cohen:      

That’s exactly right. And that’s where we talk about personalized medicine as far as the patient’s own disease but it’s also personalized medicine in that we personalize it to the patient, and their life, and what works for them. So, I take care of some patients so I’m at Clifton Road here in Atlanta, but they may live 150 miles away, and they may or may not have somebody to drive them to campus. And so, for them trying to go on a combination IV chemotherapy where they have to be here three days in a row every month is just not feasible. And so, for that patient, regardless of what their disease biology is, we may think about an oral therapy that they can take at home.

On the corollary we have some patients that are already on 15 pills at home, and the thought of adding an extra pill that they have to take every day is just not something that they necessarily want to do, and for them they like the security of knowing they come in, they get their treatment here with us, and then when they leave they know they’ve gotten their therapy. So, you really have to take into account the patient and their wishes their support system, other medical conditions that they may have that may interfere with their ability to tolerate therapy.

And so, it really is, there’s the disease component, but then there really is the patient, and it’s something that we truly think—I think a lot about anytime I’m starting a patient on treatment. And I have a pretty extensive discussion with them about the pros and cons and why one approach might be better for them.

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