EDUCATED PATIENT® Chronic Lymphocytic Leukemia Webinar

October 8, 2020
CURE Media Group

Join us for our Chronic Lymphocytic Leukemia webinar where experts discuss CLL information highly relevant to patients, caregivers and advocates right now. Participants will have the opportunity to submit questions to be answered live by our expert panel.

In the latest EDUCATED PATIENT® CLL Webinar our experts discuss CLL information highly relevant to patients, caregivers and advocates right now. Participants will have the opportunity to submit questions to be answered live by our expert panel.

Transcription:

KRISTIE KAHL:Hi everyone, and welcome to today's live broadcast, the Care Educated Patient webinar, and CLL.I'm Kristie Kahl, Editorial Director of CURE.We are pleased to bring you this webcast presented by CURE and in partnership with the CLL Society, AbbVie, and Genentech.

We have a few important announcements before we begin.We encourage you to ask questions during the event, which you can submit by typing them into the Q&A box.You will be receiving a survey via email tomorrow.As a thank you for watching the whole event and completing the survey, you'll be entered to win one of three Visa gift cards.

We are pleased to be joined by our moderator, DR. Danielle Brander, Assistant Professor of Medicine at the Duke Cancer Institute; DR. John Allan, Assistant Professor of Medicine at Weil Cornell Medicine; and DR. Mark Hoffman, the CLL Society San Diego Support Group Leader.Thank you for joining us today, and I'll now pass this off to our moderator to begin the discussion

DR. DANIELLE BRANDER:Thank you, and welcome to everyone.Over the course of the next hour, we're going to divide our discussion into four main topic areas, and then have time at the end for questions.So, as was mentioned, please feel free to submit questions along the way.

And to start, we want to talk about different treatment options for CLL and particularly focus on the duration of these therapies.And now, we consider many blood cancers, including CLL, to be a chronic condition, and patients can be on therapies for various amounts of time.So John, if you could start by giving a general overview of the different treatment options for patients with CLL and specifically how they may vary in the duration that patients are on therapy.

DR. JOHN ALLAN:Yeah, great.Thank you for the invitation to be here.It's a pleasure.And this is a great opportunity to share some insights and thoughts and education and kind of see how we all practice.I appreciate that.

You know, with that question on treatment duration, obviously as you stated, there's a lot of different options available to us, to physicians and to patients nowadays.We are kind of emerging away from the era of chemo immunotherapy, which obviously has some benefits obviously.And one of those being is that it is kind of a fixed duration-type approach.There's obviously a lot of downsides, especially compared to some of the new treatment options that we have.

And so, I'll try to focus on those much more because I think those are way more relevant to the patients, as well as to us on the future discussion about kind of why we're all here.

So, you know, when you look at BTK inhibitor approaches, the standard of care is continuous therapy.A lot of people shudder at that and don't want to think about continuous therapy, but I really look at it as a chronic disease that can be controlled for a long, long period of time.And it's taking a pill a day, and you can get a lot of durable efficacy.

Some of the studies that have been reported have been reported now up to five years of median follow-up, with some patients on those studies out eight plus years.But this is continuous treatment and we know it's safe, we know it's very effective.And every year that goes by, there's new updates, and we always learn the number of patients that remain on these therapies for that long.

So, when you look at a monotherapy BTK inhibitor approach, you can think of continuous treatment, but that's not a bad thing because these drugs have low toxicities, patients tolerate them well, they can stay on them and be very compliant, and we know these drugs work for a long, long period of time and control the disease.

You can shift the set to talking about fixed duration now with Bcl-2 inhibitor of Venetoclax-based approaches, plus or minus combination treatment with Anti-CD20s.And that is a fixed duration approach.Again, this is complicated because there are various durations of treatment with this based approach.

When you are talking about first-line treatment, we think of one year of treatment, and then being able to stop patients off of the drugs and let them go for a period of time.And we're still following these patients out, reports out to now four plus years and we're learning how well people do off of therapy with this base approach, which has some benefits of getting very deep remissions.In relapse settings, it's two years, and we're learning the optimal time.So, we don't quite have that hammered out right yet, but we're learning that.

And then, obviously where research is going, we are looking at combinations of the BTK inhibitors plus the Venetoclax-based drugs.And Mark will talk potentially about his experience with some of those approaches, but that is also fixed duration typically in general, we believe, and also is in research settings at various time points.Some are one year of treatment, some are based on response and how fast it takes you to get there, and some are based on a set amount of 15 months of total treatment.

So, to answer your question, Danielle, it's a complicated situation we are in CLL.You need to talk with your physician and your provider about which approach might be best for you.But, like I said, don't shudder at the thought of a continuous treatment because, like I said, these drugs can be well tolerated, they're extremely durable, and that is basically where the bar is set.But we are trying to get away from that, I do believe, because most patients don't want to be on these therapies.

But that's really what it means, and it's not a one-size-fit-all for all patients, and really is specific to the treatment approach employed, as well as kind of the goals that you want to get out of your therapy.So long, long story short there,

DR. BRANDER:That was a lot.I always say that's a hard question to tackle because I think treatment discussions--not just talking about efficacy or side effects but how to factor this in--have, in a good way, hopefully become very long conversations with patients because there's a lot of factors to take into account.And in a minute here, I do want Mark to share what factors play into consideration of how long to be on therapy.

I'll just say, to summarize the points that you've made, John, is the factors that go into consideration for how long patients should be on therapy, part of the factor, of course, is the regimen chosen.Traditionally, chemotherapy was for a certain amount of time, as long as tolerated.And now, as you mentioned, for the newer targeted therapy, part of the consideration is what regimen it is.And outside of a trial standard, the BTK inhibitors are usually given continuously until there is a problem, and that problem is either the CLL becomes resistant, which for most patients as a first treatment is less common than sometimes the problem that our patients run into, which is side effects that can't be managed.

Some is the therapy that is chosen or, as you mentioned, that the Venetoclax is typically given in a time-limited therapy, depending if it's a first treatment for one year, or as a second treatment, or beyond for two years.

So, those are some of the considerations, just based upon the regimen chosen as well as what might happen along the way.But another important factor, Mark, if you could just comment on, from your experience and from learning the support group, what factors really go into, or what variation do you see in the duration of therapy, how important that is and to making a decision on treatment?

MARK HOFFMAN:Yeah, I feel the duration has become a bigger, more important option that in the past, it basically for a while was single agent Ibrutinib and then maybe Venetoclax.And we didn't know about fixed duration in the beginning.But now that we have these options, some of the people in our San Diego group were talking and they're like, do I want to have to stay on one thing or can I get a situation where I can get a fixed duration and finish quickly?

One thing I'd like to say also, first of all, I was introduced as DR. Hoffman.I'm not a doctor, but I play one on TV, I guess.But the one thing, I want to thank CURE magazine and CLL Society.One of the points I want to make, first of all, is it's very important, the education and to really know what's out there and what's possible.

When I first started, backing up a little bit, I was not at UCSD, I was at a cancer center.And the original doctor, fortunately I was told to get a second opinion at UCSD, and I was working with CLL Society and the UCSD support group.So, I kind of knew what I needed to do.

But at this other institution, I was going to both of them, the doctor, after six months, was like, FCR, it's the gold standard, let's go.And I was like, what? And he's like, yeah.And I'm like...Fortunately, I was educated.I was like I don't think we ever checked my genetics.He's like, oh yeah, we didn't do that, so let's do that.

And so, I ended up not being at that institution and moved to UCSD.And when my genetics were checked, I ended up having 17p deletion.So, that knowledge was just practically life-saving.And so, everybody, to be more and more educated, is just crucial.But when it comes to the duration, my opinion is that if you can be on a fixed duration and get off after...

So, I'm on the CAPTIVATE trial.First of all, I progressed very quickly.I can show you some pictures before...I was diagnosed in 2015 and by 2016...I don't know if you can see my nodes were huge and partly they were bigger because I was waiting for the trial to open.But then within a week, the Ibrutinib was able to bring my nodes pretty much totally down.

But then from there, I was able to go for three months on Ibrutinib, and then they brought in Venetoclax, and that was able to bring my absolute lymphocyte count down to like one and a half or so within weeks.And fortunately after 15 months total being on therapy, I was able to get to undetectable MRD.

And so now, it's been almost two and a half years being without...Well, as part of the protocol, I'm on the arm, which is either Ibrutinib or placebo.But because of the side effects of Ibrutinib, I'm 99.9% sure I'm on a placebo.That's where I'm at this point.

As far as acalabrutinib, the drugs there...Ibrutinib, it wasn't too bad for me, but there was a bit of fatigue.And the things for myself, it just so happened, the brittle nails and the fingertips bleeding and that, it wasn't bad, but it was just kind of annoying.And so, to be off of it, it's definitely nice.

DR. BRANDER:Well, thank you for sharing that and of course, just reiterating how appreciative we are of having this opportunity to be part of the education.But also, to your point, to patients and their caregivers who have participated in clinical trials because of course that's how everything that we have learned and these options to become available.

When I think of all the time and energy that patients and their caregivers put into that, it's definitely much appreciated in thinking how much it's improved things.And then, given other options, such as you mentioned, especially for patients with markers that previously would not have responded very well at all to chemotherapy, such as deletion 17p or TP53 mutation.So, again, thank you for sharing that,

John, if I could just follow up on what you said in terms of the duration of therapy.You mentioned a couple of times about patients being able to stop therapy, particularly on Venetoclax regimens.How do you know if patients can stop therapy? Do you usually stop after the fixed duration, or are there other considerations maybe not just with Venetoclax, but other treatments where, you know, patients have reached a point where they can safely or, at least for a period of time, stop therapy?

DR. ALLAN:Yeah.It's a great question and also it's a complicated answer as well, so I'll try to be succinct and brief about it.When you're using Venetoclax-based treatment, the benefit and the pro of this drug is, one, it has low toxicity but, two, is that it can get into what's called MRD, minimal residual disease negativity, meaning we cannot find CLL cells floating around in the blood or in the bone marrow.

And that has correlated with better outcomes for patients that are able to achieve that.And we know that it seems that drugs can be safely stopped when patients achieve that kind of marker, that biomarker that we look for now in clinical trials and sometimes even in routine clinical practice.And fortunately in the studies, the majority of patients get there, actually.

And so, when we are using a Venetoclax-based approach and following the frontline study that made that an FDA-approved indication and treatment regimen, I frequently will look for that.That gives me some certainty that I can safely stop and patients are going to go a really, really long time and be well.

With that said, the guidelines actually don't recommend to look for that marker.And so, when we use that based approach, even if patients don't get to MRD negativity, and we find a little bit of CLL cells floating around, we can still stop.And frequently I do because most patients have a very small amount of CLL floating around.

And the whole reason why we chose that approach was to have a fixed duration, you know, especially our younger patients and things like that, where they do not want to be on a drug for many, many years.And so, what we seem to know at this point, it also seems safe that you can stop those patients, and they can have meaningful remissions and holidays off of drugs.

When you talk about BTK inhibitors, it's a little bit more complicated.We do know, as Mark alluded to before, that many of the patients in his support group, they're on the drug for many years and there's still a little bit of CLL floating around that HLC has never normalized.Well, we know when you stop the drug, whether it's for toxicity, or you've just been on it too much, or financial reasons, or whatever it is, that inevitably, those cells will start to grow back.

And so, is that necessary detrimental? It depends on the biology of the disease, the risk factors of the disease.These are all things that we take into account. At least the physician will think about when they talk about potentially stopping and giving a holiday, so to speak, if there was an intolerance or something along those lines.

The patients that have high-risk disease features, I think we still are a little bit concerned about having to stop treatment in them and we don't know the best approach necessarily for those.But when you use combinations and you can get into deep, deep remissions, I think even those patients are going to have very meaningful remissions off of these drugs.

And so again, really complicated questions.I'm trying to boil these down into very simple, straightforward answers, but unfortunately we are not working with evidence necessarily, strong evidence, head-to-head randomized data that we can state these are the patients that can stop, these are the patients that can't, these are the tests that we use to determine that.We just aren't there yet.It's evolving.

That's why this field is exciting.We've got really homerun-hitting drugs here that benefit almost every single patient out there.And so, I think that's what I try to focus on with my patients, not necessarily get into the weeds and the nuance because it's opinions.It's opinion pieces out there right now, and I think that's kind of the situation we're in.And only with time, time being years, are we going to figure some of these answers out for how to identify the best approaches for patients.

DR. BRANDER:Great.Well, thank you.And just to your one point, in terms of the BTK inhibitors, like arbutin or acalabrutinib, though we typically don't stop after a certain duration, if patients do stop because of the unmanageable side effect, they don't necessarily have to start the next therapy right away.There is evidence from trials and just what we've seen that some patients can meaningfully have time off if that arises, even though you might plan for it.So, thank you.

MR. HOFFMAN:Oh, I hear, if you're having problems with one, like Ibrutinib, if possible, I found doctors recommended if you could stay on that one while bringing in the second one is many times safer in a situation where the disease is kind of starting to go out of control a bit.

DR. BRANDER:Yeah.No, that's a really excellent point.So, if it's the case of a side effect of Ibrutinib or acalabrutinib, you can usually stop and have a period of time.But if the leukemia is becoming resistant and starting to have progression, that's a really good point that it's important to try to stay on the Ibrutinib or acalabrutinib until you're ready to start the next therapy so that there isn't a rebound and a faster progression.So, thank you very much for importantly pointing that out.

So, we're going to move into the next section of talking about treatment options and just really highlight here about the oral agents and adherence to taking these medications.So, just to summarize, we've mentioned them already, but we often refer to these oral or pill taken by mouth drugs by the type of inhibitor they are, so the BTK inhibitors are Ibrutinib and acalabrutinib.Venetoclax inhibits something called apoptosis.Those are all approved for patients that have had treatment before, or as their first treatment.

For patients that have previously had treatment, there are also oral agents, though not used as frequently as much, that inhibit something else called PI-3 kinase inhibitors, such as Idelalisib and duvelisib.

So, one of the questions that is asked is, how important is adherence and taking these medications every day? And I would say that again, has John mentioned before, it's hard to get clinical trial data evidence for this because often on clinical trials, there's multiple people helping keep track, and there's overall pretty good drug adherence.Off of a trial, it's real-world things happen and come up.

But from the evidence that we see, patients that have to hold their drug for a specific reason, like the BTK inhibitors, you have to hold around procedures because there is a risk of bleeding.That kind of holding or adherence is not what we're talking about.That doesn't appear in some studies to significantly impact the control over the leukemia long-term.

But patients that have to come off treatment a lot due to side effects, or not being able to fill a medication for financial reasons, or other reasons of forgetting to take medication.That may be a risk factor eventually for the leukemia becoming resistant to that medication.

There are other things such as, for example, in starting Venetoclax, especially during that first period of time when you're trying to get up to the full dose, that if a lot is missed, you almost have to start over in monitoring for what we call tumor lysis.

So, one of the questions I had for you, Mark, and maybe some of the feedback to you get through your support group is how can patients improve drug adherence? Or, what are some of the resources, tips, or tricks you've heard that can be helpful?

MR. HOFFMAN:Yeah.I think for the most part, most of the patients are pretty good about adherence.I mean, the biggest trick that I found is to get a classic pillbox and have them in there by day.And so then, when the day is gone, you'll know it's gone.Where sometimes, I think we've all done it, where you have it in your bottle and you're like, did I take it? Didn't I take it? And so, just doing that and having it there to go through is important.And the adherence, I think, is very important.

But some people do...I've heard that if it does give a little bit of fatigue, sometimes they will skip a day or something like that if they have an important event the next day, which I don't necessarily recommend, but some people have done that.But for the most part, everyone I know tries to adhere to it during treatment.

With a clinical trial, it makes it easier also because you have...As far as a shoutout to clinical trials, a lot of people are like oh, it's too much work, too much testing.But, it's actually on one hand.On the other hand, it's actually really good because you have a clinical coordinator who helps to coordinate the appointments.

And there are extra tests, but we've had people in our support group that one in particular, who found lung cancer, being on a CLL clinical trial and they operated.The CLL doctor encouraged the lung cancer doctor not to do heavy chemotherapy and they didn't.And 12 years later, she's still fine.But fortunately, because of the clinical trial, they found it early.

DR. BRANDER:Yeah.John, I don't know if you have anything to add in terms of resources, or what you do in your clinic for patients that need resources for being able to stay adherent to their medications?

DR. ALLAN:Yeah.No, I mean, I think specific resources or tips.Resources, there's lots of resources for our CLL patients and that's great, and the CLL Society is one of them.I always direct my patients to there because you can get in touch with chat groups, you can find these webinars, you can learn where there is access, and access experts and expert opinions, and things like that that you may not be able to in the region that you live in the United States or even the world.So, the Lymphoma Leukemia Society, Lymphoma Research Foundation, these are all great sites to get education about the disease, about these drugs, and things along those lines.

Regarding adherence, I think that comes into...If you notice a toxicity, you know, being in touch with your practitioner, and getting to know the physician assistant or the nurse practitioner.And reaching out to them and shooting an email, or putting a phone call in to say is this normal or not, so you can know what to expect when you start to take these drugs, and trying to be educated there.

And I also just encourage my patients not to stress too much about being 100% on time.You know, I had a patient had an alarm clock on the phone going off twice a day at the exact same time.I put myself in that position, I'm saying I wouldn't want to have to be beholden to this.And if you're at a movie theater or whatever it is, to have that thing going off and being worried about taking it.

So I say, you know, there is leeway built into when you have to take your medication, and it doesn't have to be 100% on time every single day.And that there is hour windows on either side that you can take it a little bit earlier, a little bit later, and adjust it to your life, which helps increase compliance.And understanding that to knowing that if you came home late that you can still take that.Those type situations.

So, those are tips and tricks that I say to not stress so much on, on the exact timing of things.But those other resources I spoke about, you can talk to your colleagues and other patients, and get tips and tricks from them as well.And I do encourage that, too.

DR. BRANDER:Okay.Well, thank you.

MR. HOFFMAN:I felt - - taking it, as far as their Ibrutinib and the Venetoclax, I think I found the Venetoclax was a little bit better to take right after dinner, whereas the Ibrutinib, when it mixed with the food, wasn't as good.So, I would take the Venetoclax right after dinner, but then would take the Ibrutinib before I went to bed on more of an empty stomach.And then, if there was some fatigue, I got the most fatigued during the night.But everybody kind of gets their tricks and such.

DR. BRANDER:Yeah.Now, again, a very good point.I learn so much from patients.Or, as you mentioned, when you're on clinical trials or some combination therapies, you might be taking more than one.And they don't necessarily - - taking every day, if you talk with your team, need to be taken at the same time a day.And so sometimes, that helps with side effects, as well, and that all plays into being able to adhere to the regimen.Great.

Well, I want to make sure we have time for our other sections here, so we'll move into our next section, backing up a little bit in what we've alluded to, which is how to decide on treatment.So, the physician and patient conversations.

So Mark, I'll have you start because I believe you've mentioned some of this before.But what factors do you or do you hear that are taken into consideration when you're deciding between these treatment options? Before, we focused on duration, but what other things, like efficacy or the quality of life are some of the side effects? And how do you learn more about them to be able to make that decision on the treatment choice?

MR. HOFFMAN:Okay.Well, first of all, you know, education is very important.The CLL Society's website and then the forums.The groups are very important where you can hear everybody's opinion and such.And the interviews that you guys do at the conferences that are on the CLL Society website, you can learn a lot.So, everybody kind of has to find what they're looking for.

I guess a big part of it also is just what's available as well, from both standard of care and clinical trials at whatever institution you're at.In my experience, I was fortunate.I found out I was 17p deleted, so I wanted to have the strongest combination possible.And fortunately, the CAPIVATE trial opened up at UCSD and I was patient number one.

One of the reasons my nodes got big is I was waiting for the trial to open.But fortunately, that worked very well and cleared out my CLL.But some people feel that then you're using both of these good drugs at the same time.Other people have the philosophy well, I'll just go on Ibrutinib or Ibrutinib with gazyva, or a BTK or acalabrutinib.And then, if that stops working, then I'll switch to the next one.Because my combo is still not available as a standard of care.

So, as far as standard of care, you have to go what's available now, which I believe is Ibrutinib with gazyva, or monoclonal antibody, or they just approved Venetoclax with gazyva as well, as far as what's available.And then, I'm not sure what the status of acalabrutinib is at this point.But overall, I feel very lucky that we're just taking pills or even some of the combo trials where you're doing

IV Anti-CD20 antibodies with the pills.It's still much, much better than the cytotoxic chemotherapies.

Unfortunately, I still see online and a lot of people from institutions that either are not that aware of the targeted therapies.They are still using the FCR or BR in some of the places as well.So, I feel the pills are a much easier and much more advantageous option.

DR. BRANDER:And now, just to answer your point, as first treatment or for any line of therapy, acalabrutinib is approved along with Ibrutinib and Venetoclax, plus or minus the Anti-CD20 antibodies as you, as you mentioned.And not only for some of the side effects that you pointed out, but of course clinical trials showing for patients the benefit of some of these therapies.

So, the same question, John, just maybe in a little bit different way.This was asked kind of assuming that all treatment options were equally being offered.Could you comment if there is any specific other medical conditions, or medications, or anything that might affect what you tell patients in terms of what options might be best for them as a treatment?

DR. ALLAN:Yeah.No, absolutely.So, this conversation used to be very simple, as you stated very early on, when we had Ibrutinib as the only option really to offer patients.And now, it has become a very long discussion:pros and cons of each approach, toxicities of each approach.

So, when you think about BTK inhibitors, there are certain side effects, especially cardiovascular side effects that we think about that may not be best for patients with a cardiac history or history of arrhythmia such as atrial fibrillation.And so, because these drugs have been known to induce these arrhythmias such as atrial fibrillation, and have some cardiac effects such as hypertension, and can be problematic for certain patients that are coming into a situation already with hypertension and/or atrial fibrillation that's not very well controlled, so on and so forth.

Additionally, the BTK inhibitors have other toxicities such as rash, arthralgias, potential diarrhea.And so, patients with underlying baseline arthralgias, joint aches, osteoarthritis, things like that, it could potentially exacerbate and make those worse over time and more difficult to tolerate.So those things come into play a little bit with, you think about BTK inhibitors.

When you think about a Bcl-2 approach, I start to think about age a little bit.Because it's fixed duration, it becomes more attractive for our younger patients, patients in their forties and fifties, and even in their sixties.Whereas maybe it's a little less of an issue in your 70s, mid 70s and 80s, and even 90s, where I treat many patients, where stopping is important.So, that becomes a factor when I think about that approach.

And then obviously, when you use Venetoclax, you're looking at the major toxicity there of tumor lysis.And so, you need to have very good functioning kidney function in order to be able to tolerate the fluid that sometimes we need to give you, and then be able to drink a lot of fluid.And that comes into play with cardiac function, as well.You can't have CHF and things like that because there is a need to potentially to give fluids and tolerate it.

Additionally, you need this good kidney function in order to flush the system and in order to be able to tolerate any cell death that may occur from the drug that's killing off those CLL cells.

So, those things come into play as well as the disease bulk a little bit, when I think about specific approaches for patients.But it's really based on toxicities and those comorbidities that a patient may be bringing into treatment initiation coming up and starting on a therapeutic approach.

DR. BRANDER:Great.And of course, just to reiterate, this is a lot of information, but of course the hope is that when you find your oncology and CLL team, that you start to have some of these conversations as maybe you see the CLL progressing.So, this isn't something you have to take in all at once, and have time to get these resources and think about some of the options or trials that are best for you.

Mark, if you have a comment while we're talking about these long conversations, what's some of the feedback or what are your thoughts of ways that these conversations between patients and physicians can be improved in talking about treatments?

MR. HOFFMAN:Well, I guess being well-educated, and I think it's important in the doctors I find is if you can get a concise list of your questions to start.And a lot of times, I'll give that to the nurse when I'm getting the pre-tests done and stuff for the appointment.And then that way, the doctor can look it over and have answers when they come to see you.And you have to have, as Brian says, prioritize though to have the most important ones first, and hopefully there is time to get to everything.

But one other thing I wanted to comment on is tumor lysis syndrome with Venetoclax.It is a bit of a problem, but now with a lot of these combo trials, or with proper treatment, like with mine I had Ibrutinib for three months.So then, I was brought down to the low-risk category from a lymph node standpoint.And then now, we have it where you start out at a 20th of the normal dose and ramp up.

So, tumor lysis is a concern, but I see it more of a good thing than a bad thing in that it means it works too well and it crashes tumors too quickly.And so, I think as long as it's watched and controlled, it's not necessarily a bad thing and means that the drugs work very well.Unfortunately, when they first started Venetoclax, they didn't know how strong it was and there were two deaths.But since then, have there been any deaths with ramp-up of Venetoclax? I don't even know.

DR. BRANDER:I think to your point is, how do you make it safer and reassess tumor lysis risk? So in your case, you were on a clinical trial.For other patients, they might start the antibody treatment first, and they often take a step back and relook at what patient's tumor lysis risk is, and decide if the monitoring is needed in the hospital or can it be done in the clinic.And then, as you mentioned, there is a ramp-up part.

So, just being educated on the things that you can take from a safety perspective and what might put you at higher risk, big lymph nodes before you start the Venetoclax, high white count, the kidney function slower.And then, as you mentioned before, just receiving treatment at a place where you feel comfortable with the team, that they're going to get the results back first and that they've used this regimen frequently before, so.But that was all very helpful.

And the last part here, I do want to just talk about, we had some questions submitted about the psychosocial aspects, some of the stress and anxiety between the treatments and the testing that patients have to go through.And I might ask sometimes with CLL being a chronic disease, how does anxiety come into play for patients or what patients report to me?

And I think, as Mark and John, you both mentioned before, that what I hope to do is, or our whole team hopes to do is create an environment where patients that are feeling that stress and anxiety feel like they can be open and honest about it, and that we can help place in contact with resources.

Now, in the era where there is a lot of telemedicine, in some ways that has helped a lot because patients that come from farther away that maybe before would have been really hard to meet with a patient support group or a counselor now can do some of that, depending on anxiety.

Some of it I think is also where patients are in finding out about the diagnosis and, just as you said, try to prioritize questions and take things in sizable chunks, otherwise can be very overwhelming to want to know everything all at once.

And then lastly, I tell patients to keep asking the questions because the answers will mean different things to you, depending where you are in your journey.What the same answer maybe you heard when you were first diagnosed starts to mean more as you go through the process.

And so, John, if you want to maybe comment what's available for your patients, or what you've heard patients report to you of what kind of outlets that they can use around the time of their diagnosis in terms of some of the psychosocial stressors that they experience.And maybe you could share what you have at your center, or what patients have reported that they found to be helpful.

DR. ALLAN:Yeah, I think that's where seeking a physician that has some experience with CLL can be beneficial because you can identify risk factors and biological risk factors that the vast majority of CLL has lower risk features.And so, if you identify those, that can help ease some anxiety for many patients to where they don't have some of these high-risk features, and therefore they know that they may go ten-plus years before they might need treatment.

And so, that's where the experience of your physician and trust with your physician comes in, and having these conversations to really go through your disease, and what does this mean for you? Because people will read potentially scary things that are out on the internet and things like that that don't necessarily even apply to them.And so, reassuring them goes a long way in easing some fears.

At our center, we have a psycho oncology clinic basically, so we have psychiatrists that deal with our oncology patients only.And so, we refer to them and can get them in very quickly and easily.And I know many patients have given me positive feedback of meeting with them and the psychotherapy, and things like that that they can get through that type of a process.

And then additionally, I find a lot of patients rely on these chat groups, and the CLL Society, and the CURE magazines of the world, and getting information from their friends and family members, and other people going through the exact same thing that they are who might be three or four months ahead of them in it, or even years ahead of them in it, to where all of a sudden they're like, wow, these people are doing really well and are getting education.I've seen our patients being very well educated in terms of the CLL.They're asking for, you know, these tests and they're keeping us honest.

And so, those things all go a long, long way at easing some of these anxieties because obviously this is a disease.You get diagnosed with it and many times, you don't do anything about it.And that's uneasy because it's a unique type of cancer in that situation.And I empathize with my patients what they go through, and I can only imagine some of the stress and anxiety that that can present on a daily basis, thinking about it.

So, I try to reassure them.I try to be there for them.And it really comes to developing a good rapport with your doctor, the physician extenders, the whole center that you're working with, and getting some information, and just asking these, these tough questions.And not being afraid to ask your doctor.We're here for you, and that's the whole point why we got into this.

And I find sometimes, patients are intimidated for various reasons and you got to just ask those questions.You've got to build that rapport, and you got to build that trust.And that goes a long, long way at easing some fears.

DR. BRANDER:That's great, and a great transition to what I wanted to ask Mark to end some of our sessions and then get to some of the questions being submitted.Mark, if you can take from that and just comment on what you feel and what feedback you received of why support groups are so important for patients to consider.And then, maybe also what are the different levels of involvement that patients can have with support groups?

MR HOFFMAN:Yeah.The support group has been very helpful.But also, like the doctor mentioned, though, the knowledge is very important from the doctors as well.I think the statistic is 30% of CLL patients never need treatment.And so, that's reassuring.And it is kind of a counterintuitive disease also, where you get in and then they're like, okay, you have it, but don't do anything.

But yeah, going to the support groups.A support group has been really good.I know when I started I'm like, oh, I don't need it.But then I went and I'm like, wow, you're talking to the real people that have it, and you can just get the feel and different situations.

I remember I was given the opportunity of a clinical trial and I was talking to one of the women in the support group and she's just like, oh, there's always clinical trials.Don't worry, there'll be another one, if you don't want to do this one.And then, you can talk about different treatments and different things.And so, the support group is very, very important.

Not to mention, there are other resources online as well, Health Unlock and other ones too that you can pose questions online.

DR. BRANDER:Great.Oh, wonderful.Well, thank you.We've received a couple questions throughout the way and so, John, I'll start with you.We had some questions and we've been talking about BTK inhibitors being continuous therapy, which BTK inhibitors including ibrutinib and acalabrutinib being the two approved for CLL.

So, what's the length of time on these continuous therapies till you generally see an effect from the Ibrutinib or acalabrutinib really? And what's some of the longest lengths of time that you've had patients on these agents?

DR. ALLAN:Yeah, so it's a great question, and Mark alluded to this a little bit earlier, is that once you start taking these drugs, literally within days to a week, these lymph nodes really just disappear.And it's really amazing to see such a response.

So, all of these drugs, whether it's been Venetoclax or Ibrutinib or acalabrutinib, they all have a rather rapid onset of action, and you start to see shrinkage in your white count and/or lymph nodes very, very early on, within days, or even a week or so.

With that said, people can stay on these drugs for a long, long time because it works so effectively and so quick.I've been doing this now almost over five years and I came in right as Ibrutinib was basically being approved front-line.So, most of my patients that I've started out five years ago remain on these drugs and are doing well.And I've had very few patients have to stop them either for toxicity or the disease has started progress.

And for those very few that have...Venetoclax is available, other drugs in the class.There are clinical trials, there are a lot of things to offer patients, but the data has followed patients out to eight plus years now taking these drugs.And so, there is no real time limit.They do appear safe.There has never been a long-term safety signal that has come out necessarily that would make physicians in the field and/or patients hesitant to continue these past a certain time point.

Obviously, eight years in the scheme of humanity and clinical trials, and all of these things is still a relatively short period of time.But with that said, that's still a significant period where we have been calling patients, and have established the safety and efficacy over that period of time.So, they are really remarkable drugs and agents, and they work quickly, and there is no time year or period where if you've met that time point, that's too long.

And so, I encourage patients to stay on it as long as it's working.And, we can have confidence in it continuing like that.

DR. BRANDER:Yeah.No, I think that's a really nice way to summarize it.And in terms of the question of how fast they work, of course it depends what aspect that you're looking at because often, the drug is very quickly--and Mark, you can correct me how short interval it was between those pictures--but the drugs like Ibrutinib or acalabrutinib, the BTK inhibitors, they can push those leukemia cells out of the lymph nodes or the spleen pretty quickly, so the white count goes up because they're being kind of pushed out of the way.

So then, it can take a while for that white count to come down, though it usually, at least in my experience, usually peaks in the first couple of months, when you're taking the drug as a single agent, in the first two or three months.It just then might take months and months or years for the white count to completely come down, or it never quite comes down.But Mark, do you want to comment on that? How fast the lymph nodes, you noticed?

MR. HOFFMAN:Yeah, fortunately, the lymph nodes came down literally in like three, four days, which was just amazing.I was treatment naïve, so I think that is also a factor, that the drugs work the best when you're treatment naïve.Which is something I should comment on with the clinical trials.Treatment naïve here, you're only treatment naïve once.And so, that is a factor when you pick your first trial, if you're going to do a trial because once you're not treatment naïve, you're not always eligible for some of the trials.

And then, the other comment on the clinical trials is you can get some of the best care with clinical trials, but you got to be careful with some institutions.They have like a really good arm and then like a really old arm or something.And so, you want to make sure the trial is such that whichever arm you get is a pretty good arm.

But basically, yeah, my nodes went down, I was fortunate that went down, like, within a week.A and for some reason, because I had some of the higher risk factors, a 17p deletion, the classic is the white count goes up.But mine went down right away, and continued on down on Ibrutinib.

DR. BRANDER:Right.We had another question about Ibrutinib or BTK inhibitors, which is the dose.So, we haven't spoken a lot about the dose, but patients typically start on a certain dose regardless of how old you are, or what your numbers are, as long as there aren't other medications that might interact.So, patients usually on Ibrutinib or acalabrutinib start at the same, all start at the same dose, but you might change that dose over time, if there's a side effect.

However, if patients are on other medications, that might directly interact with how the Ibrutinib or acalabrutinib, or Venetoclax for that matter is eliminated by the body.So, in some cases, it's completely acceptable that you might be recommended to be on a different starting dose because your body essentially is seeing the same dose, even though you're taking a lower dose, because of that drug interaction.

In other cases, sometimes your physician might recommend a change to the dose because of the side effect that you are experiencing that might be related to the dose, so things like muscle or joint aches.If after a while a lot of different measures are tried, your treating physician might recommend to reduce the dose.

One of the questions we got is if patients are on blood thinners and taking Ibrutinib or acalabrutinib, now Ibrutinib and acalabrutinib are BTK inhibitors, you have to watch closely for bleeding because it affects not necessarily the platelet numbers you have, but how well the platelets stick together.In a way, it almost affects the platelets, similar to how aspirin makes your platelets not as sticky, so to speak.

So, one of the questions we got is if you're on a blood thinner, do you change the dose of the ibrutinib or acalabrutinib? And not necessarily.Like John mentioned, being on a blood thinner might be part of the discussion of what treatment is best for you.The dose is not necessarily changed.However, sometimes when you're on a blood thinner, you might also be on other medications, or something might have happened before to make your treating physician concerned about taking the full dose.

What we know is that people that have to reduce the dose due to a drug interaction, again, that shouldn't affect how efficacious the drug is because your body is seeing the full dose.But in many cases, there are some trials that if patients have to lower the dose due to a side effect, or due to a concern of a side effect, they can still have really good results.

So, it is a bit of a complicated question, but it's a really good one to bring up.And if you have a question, just ask your physician or treating team, or ask the pharmacist at your oncologist to just explain to you again the reason for that dose.

So, very lastly, John, we had a great question about talking about treatment.But backing up a little bit to Mark's point, about 30% of patients never need therapy, or a lot of patients that might be joining here are just new to the diagnosis.So, what are the things you tell patients first diagnosed of what to watch out for? And how do you explain the main reasons that are the indications for needing to start treatment?

DR. ALLAN:Yeah, so that's where a lot of the prognostic factors will come into play.And when I see a new patient, I send all of this stuff.I send the FSH and the IGHV, and we even sequence all of our patients at diagnosis, though many of the guidelines say to just do it prior to some therapy.Because as you can see in MR. Hoffman's situation, it dramatically impact on how he was going to be managed.And for the better, obviously.

And so, I send all that stuff up because you get a lot of this prognostic information.There, you can start to educate the patient and/or put feelers out there on what to expect on when treatment may be needed.Patients with higher-risk features in general need treatment sooner than those with lower-risk biologic features, potentially years difference.

And so, that helps you identify how closely you need to follow a patient, how often they need to come in and see you, and have lab work and physical exams, and so on and so forth.So, we do all of that.And I think most doctors that see a lot of CLL patients are doing that.And so, you'll get that information.

When you talk about treatment, typically I talk with my patients it being kind of five-fold reasons.The first being B symptoms:fevers, night sweats, fatigue, weight loss, usually in isolation.Not something that I'm going to initiate treatment, and usually comes about when you have more advanced disease.Progressive lymph nodes, big spleens, high white counts, other things are going on when you have those types of symptoms.

The second are progressive:lymphadenopathy or splenomegaly.This can be a little bit subjective on when to treat, but as long as there is disease activity and change over some relative short interval of time, that is showing disease activity and is a potential indication to treat.There are size criteria, but those size criteria are actually very, very large lymph nodes, and we try to prevent our patients from getting to be that bulky because it's harder to then initiate treatments on some of them.So, there's wording that says progressive lymphadenopathy or splenomegaly.

Additionally, like it grows in our lymph nodes and our spleen, it grows in the bone marrow and pushes out the good cells.So, the good red blood cells, we start to become anemic.Patients become anemic and the good platelet, the platelet count start to drop because the megakaryocytes, the cells that make those platelets are pushed out of the bone marrow.

And then, the fourth indication would be any autoimmune hemolytic anemia process that occurs, or ITP, where the antibodies and T-Cell defects that occur in CLL flare and then drop the counts really low.Not subtle.You can pick it up on labs.Usually patients are not feeling good when that's happening and they call the office right away.You bring them in, and it's very simple to diagnose.

And then typically, the last thing as a treatment indication for all the guidelines is when you see CLL proliferative.In general, it is not a proliferative disease.These cells do not double constantly.They just don't die because they over=express a protein called Bcl-2, which we target with Venetoclax.And so, they kind of hang around forever.

But when you see it kind of change and those cells start to proliferate, that is when we initiate treatment.So, a doubling time less than six months is the classic indication for therapy.

So, those are the big five-fold things that we look for.Usually, as those things are occurring, you are feeling more fatigue, you feel lymph nodes growing or new ones popping up, and those are why we bring patients back on a three-month basis, short intervals, and do exams and monitor the labs so closely.Because these things can change, and sometimes they just start out of the blue and there is no rhyme or reason sometimes.

So, we want to catch that early, rather than saying come back in a year, and then things were happening in that year.And so, we keep a close eye on you for those reasons, to look for those exact things.

DR. BRANDER:Great.Well, thank you throughout.A tough question to summarize, but that was really helpful.And again, I think those interval monitoring visits also help to have a chance for questions, and education, and discussions.

Well, again, I thank everyone for the opportunity to be part of this.Unfortunately, we are now out of time.For the audience, if you'd like to watch this webinar on demand, it will be available on curetoday.com/webinars within the coming days.

Again, I want to thank our panelists and the audience for attending and participating in today's event.I would also like to thank CURE and our partner, the CLL Society, AbbVie and Genentech for making today's educational webcast possible.Please don't forget to check your email tomorrow for the survey to be entered to win a gift card.

And thanks again to all for joining, and we'll see you next time.Goodbye.

MR. HOFFMAN:Thank you

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