CLL Treatments and Clinical Trials Archives

When it comes to treatment, CLL patients and their care partners have much to consider. There are often many options available, each with advantages and disadvantages. Some people may seek clinical trials, others may have few feasible options. Understanding treatment options, goals, and what to expect are vital to achieving the best possible outcome for you.

More resources for Chronic Lymphocytic Leukemia (CLL) Treatments and Clinical Trials from Patient Empowerment Network.

Concerned About CLL Watch and Wait? Start Here

Concerned About CLL Watch and Wait? Start Here from Patient Empowerment Network on Vimeo.

What do chronic lymphocytic leukemia (CLL) patients need to know about watchful watching? Expert Dr. Ryan Jacobs explains the CLL tests and symptoms he monitors during watch and wait or active surveillance.

Dr. Ryan Jacobs is a hematologist/oncologist specializing in Chronic Lymphocytic Leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

Download Resource Guide   |  Descargar Guía en Español

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Transcript:

Lisa Hatfield:

So I just want to take a step back and kind of looking at this through the lens of a newly diagnosed CLL patient. You’d mentioned that sometimes you don’t treat every CLL patient. So is there something, if you find a patient who does not need treatment, is there something you tell the patients as far as regular monitoring? Will you monitor them to see if it progresses to the point where it requires treatment?

Dr. Ryan Jacobs:

Yeah. And we’re fortunate that this is a blood cancer that most of the time we can follow with a simple blood count and follow the white count, follow how the…follow the health of the bone marrow by looking at things like anemia, low red cell count, or a low platelet count that we call thrombocytopenia.

So that’s the easiest thing to follow, but I’m also talking with my patients and examining my patients. I want to know if their lymph nodes are causing them a lot of pain, because we should treat that, there’s no reason they should live in pain. I want to know if they’re waking up drenched in sweat all the time, if their quality of life has been really affected by that or a dramatic amount of fatigue that we can’t explain by some other cause. And I also, of course, examine the nodes myself and make sure that there are no alarming findings there. So that’s really what’s involved with checking on a CLL patient that’s on active surveillance, that’s what we call it. And there’s a list of criteria that the oncologist should know in terms of deeming who needs treatment and who doesn’t. And so we’re kind of following the same rules, so to speak, in terms of who gets treated for CLL. 


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Emerging CLL Research | Understanding the CAPTIVATE and MAJIC Studies

Emerging CLL Research | Understanding the CAPTIVATE and MAJIC Studies from Patient Empowerment Network on Vimeo.

What’s the latest in chronic lymphocytic leukemia (CLL) research? Expert Dr. Ryan Jacobs shares updates about the CAPTIVATE study, MAJIC study, and potential treatment breakthroughs.

Dr. Ryan Jacobs is a hematologist/oncologist specializing in Chronic Lymphocytic Leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

Download Resource Guide   |  Descargar Guía en Español

See More from START HERE CLL

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Is It Aging or My CLL?


Transcript:

Lisa Hatfield:

I did a little research last night before I talked with you, and it sounds like that is something that the CAPTIVATE trial is investigating. A patient asked about that, what that trial is. And it’s music to my ears as a cancer patient to hear something like “fixed duration”, it’s also investigating a fixed duration so patients and have maybe a bit of a medication vacation. So can you speak to that trial a little bit and explain what it is a little bit on how that might benefit patients with CLL?

Dr. Ryan Jacobs: 

Yeah. So one of the best elements of treating with venetoclax (Venclexta) is that it produces a deep level of remission in many patients. In fact, when given with the monoclonal antibody obinutuzumab (Gazyva), to CLL patients receiving that treatment as a first line of therapy for their CLL, about three-quarters of CLL patients will get to so deep of a remission that we call them minimal residual disease negative.

Lisa Hatfield: 

And that’s a blood test or a bone marrow test, but more easily done as a blood test, where we can look to a sensitivity of one in 10,000 white cells and determine if there’s any CLL in those 10,000 cells. We can actually go deeper than that, but we say, we CLL patients are negative if they’re less than one in 10,000. And so 75 percent of patients will get to that depth of remission just with obinutuzumab for six months along with venetoclax for a year.

Dr. Ryan Jacobs:

So when researchers saw that, they recognized that we could probably stop treatment in those patients getting venetoclax because venetoclax yields these deep responses. And then the next kind of thought was, well, could we give a BTK inhibitor with venetoclax, but also over a defined treatment timeline and maybe get some of the remarkable benefits of treating with a BTK inhibitor but not get stuck being on therapy for years and years.

So the CAPTIVATE study was the first really to, in a large Phase II manner, look at that combination in a younger patient population, it was for patients 70 and younger. And it wasn’t in a high risk or anything, it was all comers. But they did have to be 70 and younger and getting treatment as a first-line therapy. So the combination was very effective. As of the last American Society of Hematology meeting in December, four years of data was reported and a large percentage of patients were still free of progression, over 80 percent still free of progression. And that’s three years off therapy at that point.

It was well-tolerated, not many patients had to come off due to toxicity. It was in fact, less than 10 percent had really significant toxicities requiring discontinuation. So it was a well-tolerated effective treatment.

I do have one of those studies to open at my institution, the acalabrutinib-venetoclax combination,  it’s called the MAJIC trial, and it is a large Phase III study that if it’s successful, I think would lead to the approval of giving those two drugs together. But then the extra credit question is, who should get the combination and who should get the drugs separately? And we don’t have an answer for that right now, and that’s a long topic of debate among CLL specialists. 

Lisa Hatfield:

Great. Well, thank you. So for that trial you spoke of that you’re conducting right now, is that… Is it only relapsed patients who are eligible for that? Or is that for front-line therapy.

Dr. Ryan Jacobs:

No, this is a first-line therapy that the MAJIC study is.

Lisa Hatfield: 

Oh good. That’s promising for patients too.

Dr. Ryan Jacobs:

And it has a really good comparator arm, so that won’t be a problem that the standard arm on that study is venetoclax (Venclexta) plus obinutuzumab, so it’s comparing against one of our best treatments, and so we really will get the answer of does it look better to use the BTK with the Bcl-2? Or is it not really that much better than just giving a venetoclax with obinutuzumab? And then the one obvious element that I didn’t mention that would be nice for most patients in addition to being efficacious and well-tolerated is if you could get an all-oral combination. Of course, venetoclax with obinutuzumab, you’re still getting quite a few infusions with the obinutuzumab over the first six months. So that’s a lot of time in the infusion center that you could avoid with just the combination of two oral targeted agents. So that would be a breakthrough for patients too, I think. 


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Diagnosed With CLL? Start Here

Diagnosed with CLL? Start Here from Patient Empowerment Network on Vimeo.

What do newly diagnosed chronic lymphocytic leukemia (CLL) patients need to know? Expert Dr. Ryan Jacobs explains how CLL occurs and provides an overview of treatment types. 

Dr. Ryan Jacobs is a hematologist/oncologist specializing in Chronic Lymphocytic Leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

Download Resource Guide   |  Descargar Guía en Español

See More from START HERE CLL

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Is It Aging or My CLL?


Transcript:

Lisa Hatfield:

There’s a lot going on in terms of novel therapies and new options. But before we jump into all of that, the tool box that’s expanding, can you introduce CLL and provide an explanation of what it is and what that means for a newly diagnosed patient?

Dr. Ryan Jacobs:

So chronic lymphocytic leukemia, or CLL, is the most common chronic lymphoma/leukemia. It is really both most of the time. It presents with what we call lymphocytosis, meaning the white blood cell count, and specifically the lymphocyte count is high or elevated. To call it CLL, to make that formal cancer diagnosis, we can generally take a patient’s blood sample and put it through a fancy machine that we call a flow cytometer, that looks for characteristic markers on the outside of the cells, and if there’s a bunch of those cells, we call that a monomorphic population.

So a bunch of those cells that look the same, and they’re B cells, that’s the type of lymphocyte count they are, and they’re over this threshold of 5,000. Then that is the diagnosis right there, we don’t need an invasive procedure. You generally do not need a bone marrow biopsy or a lymph node biopsy. There is in about 15 percent of cases, the disease presents with just in large nymph nodes, and the white count is normal. We call that small lymphocytic lymphoma. It’s considered an overlap with CLL, and I’ve had many patients that have started off with SLL and then eventually manifest elevated lymphocyte count later in their disease course. So it is considered an overlap, the treatment is the same for both of those disease entities.

So that’s the diagnosis of CLL and how it generally shows up initially. In a nutshell, it’s a cancer of the aging population, average age is 70. I have a lot of patients that ask me, “Why did I get CLL?” And the answer is, “We don’t know.” It’s that way with most cancers, unfortunately, we don’t know why one person gets a cancer and the other person doesn’t.

But it obviously has something to do with the aging effect on the DNA of the B lymphocytes because of how much more common it is as patients get older. 

Lisa Hatfield:

We know that therapies are evolving faster, hopefully faster than patients are relapsing, which is a good thing. So when they do relapse, chances are there will be a new option for this patient. But a CLL cure still remains elusive.

So, Dr. Jacobs, if you can speak to…we’ll just jump right into some of the newer, the novel therapies and things that are being investigated with CLL treatment. If you can just speak to some of those newer therapies, the novel pathways and targets that are currently under investigation with CLL, we’d appreciate that.

Dr. Ryan Jacobs:

Sure. We’ve come a long way in how we are managing this common cancer that’s benefiting a lot of patients. And as mentioned, with this cancer being one that is more common in the older population, we do know that the population of the United States specifically is getting older, there’s going to be more 70-year-olds. So these breakthroughs are helping a growing number of CLL patients.

Before 2014, really outside of a clinical trial, the only way we could treat CLL Is with combinations of chemotherapy and an immune therapy, like a monoclonal antibody called rituximab (Rituxan), that was kind of our first, what we would call targeted treatment outside of chemotherapy that we had, and it was, like targeted treatments are, well tolerated. It was an antibody that targets B cells specifically.

So we were combining it with chemo, we would call that chemoimmunotherapy, and it helped a lot of CLL patients. But for many, those were poor prognostic markers in particular, and those with relapse disease, chemotherapy was not very helpful, and it was quite toxic in many circumstances.

So we’ve been fortunate that since 2014, we’ve had a lot of new treatment options, and they’re targeted therapies. It’s not like non-specific cytotoxic chemotherapy, these are treatments that have been developed with specific targets in mind that are unique to the B-cell neoplasm, the B-cell cancer, the CLL. And the first of these that really changed everything was a BTK inhibitor called ibrutinib (Imbruvica), that we got in 2014.

Initially, we can only use it in the relapse setting, but eventually, in 2016, we could start treating patients as a first line of therapy with ibrutinib.  And then in 2019, we had a newer version of BTK inhibitor, we call those second-generation BTK inhibitors. That drug was acalabrutinib. And it eventually was shown in a head-to-head study to be just as effective as ibrutinib in a relapsed patient population, but it had less side effects than ibrutinib. So in, specifically, atrial fibrillation, hypertension. Cardiac toxicities overall were one that they really focused on in that study.

So as a whole, when we were choosing BTK inhibitors, we were shifting away from ibrutinib, shifting to acalabrutinib, and then just as…earlier this year, we had a third BTK inhibitor, zanubrutinib (Brukinsa), that was approved. It’s also considered a second generation BTK inhibitor like ibrutinib and acalabrutinib (Calquence). It treats CLL in the same way, in how it inhibits BTK or Bruton’s tyrosine kinase, that’s over expressed in CLL cells.

But it also has a favorable toxicity profile when compared head to head with ibrutinib, and now we have two second-generation options between acalabrutinib and zanubrutinib. And it’s not really easy for us to know between those two, which is “better.” When we decide to treat with a BTK inhibitor, we’re usually choosing between those two at this point, and we’re trying to personalize the decision for the patient, and there are some different factors they can get involved in that complicated decision.

Luckily, we are not limited to BTK as a target. I mentioned earlier, we have monoclonal antibody, rituximab like the one I mentioned, but a newer version of rituximab, a more potent version, obinutuzumab. Is one that we have available along with a Bcl-2 inhibitor, venetoclax (Venclexta). That is now, as of 2018, improved in the frontline CLL setting, also approved in the relapsed setting, of course, since 2016.  And we use venetoclax with a monoclonal antibody like obinutuzumab (Gazyva), and together they are a very potent combination that cause pretty rapid cancer cell death, as opposed to the BTK inhibitors that more put the cancer to sleep and require daily dosing indefinitely for as long as the drugs work.

And remarkably, the data on BTK inhibitors tells us that should work for many, many years. They’ve been following some of the patients that got treatment in the first line setting, and eight years out, there’s still more than 50 percent of the patients are free of progression, so they can’t even quote an average response time yet. With eight years of follow-up on the early ibrutinib patients.  The difference with venetoclax combined with a monoclonal antibody like obinutuzumab, is because it causes a more rapid cell death, you can give it on a time-defined schedule. So we tend to give it for one year in the first-line setting and two years in the relapse setting, and the antibody portion is just given for the first six months. 

The BTK inhibitors and venetoclax are oral treatments, so that’s a big win for patients to avoid the infusion center for those treatments, but the IV antibody treatments will still require some trips to the infusion center if you’re doing that combination with venetoclax. For most patients, those two targets are what we’re choosing between, and we try to personalize the decision to the patient. And again, that’s a very complicated discussion on what is “best.” And we use things like the prognostic work-up, medical problems that the patients already have, medicines that patients are on, to help make the best treatment decision for our CLL patients. But those…for in terms of how well that treats the CLL, both of those are considered equivalent options for the large majority of CLL patients.

We’ve got some things on the horizon, but in general, those are two targets that we have at this point. There is for relapsed patients, PI3 kinase inhibitors that are still FDA-approved at this time, that aren’t quite as effective and more toxic, so we sometimes think about using one of those targeted therapies if a patient has already progressed on a BTK inhibitor in venetoclax class. In the future, we are looking towards combining BTK and Bcl-2 inhibitor. Like, for example, there’s been studies already done that I’ve put many patients on, with ibrutinib-venetoclax, and I believe there’s a question about that later.

There’s also an ongoing study that I have opened at my institution that’s looking at acalabrutinib and venetoclax. So taking these two pills together in a time-defined manner, so you don’t have to take the BTK inhibitor indefinitely. And then there are some therapies that have already been improved in other lymphomas, and we wonder if they’re going to have a role in CLL eventually. So we now have bispecific antibodies, so that’s taking a drug like rituximab or obinutuzumab and adding a T-cell engager to it, so it has two targets or it’s bispecific.

And we have that drug, mosunetuzumab (Lunsumio) available in follicular lymphoma and there’s several others in development, and we’ll see how their role comes into play in CLL as well. As well as CAR T-cell therapy, where we take a patient’s T cells and genetically engineer them to attack the cancer. That’s now an approved therapy for many different kinds of lymphomas and multiple myeloma as well.

So we wonder if that’s going to have a role in CLL. But I think for the foreseeable future, it’s going to be looking first at BTK and then Bcl-2 inhibition, or vice versa. And we don’t really know which is better to go first, we think they’re both…they can both be sequenced one after the other. And then maybe it will have some of these other breakthroughs coming in and helping for after patients need something beyond those therapies.

And there’s probably going to be a lot of patients that never need anything beyond those options, those initial couple of targets, because they do so well. I think in the most immediate future, the approval that is going to give us a new great option is going to be for an alternative site BTK inhibitor, or it’s also called a non-covalent BTK inhibitor.

And there’s this drug called pirtobrutinib (Jaypirca), it has been approved in mantle cell lymphoma and likely will get approved in CLL this year. And that drug specifically is a BTK inhibitor that still works even in patients that have, say, progressed on ibrutinib or acalabrutinib or zanubrutinib. That will be a new target available for CLL patients and probably pretty quickly become one of the go-to drugs that we use for relapsed CLL patients that have already been treated with a BTK…with a traditional BTK inhibitor. So growing number of options and it’s really great for our CLL patients. 


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CLL Patient Expert Q&A: Start Here

CLL Patient Expert Q&A: Start Here from Patient Empowerment Network on Vimeo.

The START HERE program bridges the CLL expert and patient voice, whether you are newly diagnosed, in active treatment or in watch and wait. In this webinar, Empowerment lead Lisa Hatfield and expert Dr. Ryan Jacobs  provide an overview of the latest in CLL, managing CLL side effects and options for CLL progression.

Dr. Ryan Jacobs is a hematologist/oncologist specializing in Chronic Lymphocytic Leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

Download Resource Guide   |  Descargar Guía en Español

See More from START HERE CLL

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Emerging CLL Research: Understanding the CAPTIVATE and MAJIC Studies

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Can CLL Treatment Cause Gastrointestinal Side Effects?


Transcript:

Lisa Hatfield:  

Hello and welcome. My name is Lisa Hatfield, your host for this Patient Empowerment Network program. In this important dialogue, we bridge the expert and patient voice 

to enable you and me to feel comfortable asking questions of our healthcare teams with more precision. The world is complicated, as is a cancer diagnosis, but understanding your CLL doesn’t have to be. The goal is to create actionable pathways for getting the most out of CLL treatment and survivorship. Joining me today is Dr. Ryan Jacobs, a CLL expert from Levine Cancer Institute. Thank you very much for joining us today, Dr. Jacobs, we really appreciate you being here and your time and expertise.

Dr. Ryan Jacobs:

Thanks for having me, Lisa.

Lisa Hatifield:

Before we get started, please remember to download the program resource guide via the QR code. There is great information there that will be useful during this program and after. Okay, let’s get started. So, Dr. Jacobs, I’d like to talk about what’s on the chronic lymphocytic leukemia radar, and rather than saying that entire phrase each time, I’m going to refer to it as CLL, because I’m pretty sure I’ll fumble that up. There’s a lot going on in terms of novel therapies and new options, but before we jump into all of that, the tool box that’s expanding, can you introduce CLL and provide an explanation of what it is and what that means for a newly diagnosed patient?

Dr. Ryan Jacobs: 

So chronic lymphocytic leukemia, or CLL, is the most common chronic lymphoma/leukemia. It is really both most of the time. It presents with what we call lymphocytosis, meaning the white blood cell count, and specifically the lymphocyte count is high or elevated. To call it CLL, to make that formal cancer diagnosis, we can generally take a patient’s blood sample and put it through a fancy machine that we call a flow cytometer, that looks for characteristic markers on the outside of the cells, and if there’s a bunch of those cells, we call that a monomorphic population.

So a bunch of those cells that look the same, and they’re B cells, that’s the type of lymphocyte count they are, and they’re over this threshold of 5,000. Then that is the diagnosis right there, we don’t need an invasive procedure. You generally do not need a bone marrow biopsy or a lymph node biopsy. There is in about 15 percent of cases, the disease presents with just in large nymph nodes and the white count is normal. We call that small lymphocytic lymphoma. It’s considered an overlap with CLL, and I’ve had many patients that have started off with SLL and then eventually manifest elevated lymphocyte count later in their disease course. So it is considered an overlap, the treatment is the same for both of those disease entities.So that’s the diagnosis of CLL and how it generally shows up initially. In a nutshell, it’s a cancer of the aging population, average age is 70. I have a lot of patients that ask me, “Why did I get CLL?” And the answer is, we don’t know. It’s that way with most cancers, unfortunately, we don’t know why one person gets a cancer and the other person doesn’t. But it obviously has something to do with the aging effect on the DNA of the B lymphocytes because of how much more common it is as patients get older.

Lisa Hatifield:

Thank you for that overview, Dr. Jacobs. We do have CLL patients who are watching this who are newly diagnosed, they may be in active treatment, they may be in remission, they may be managing their CLL just fine right now in their lives. So we’re along the whole spectrum of CLL, so thank you for that overview. We know that therapies are evolving faster, hopefully faster than patients are relapsing, which is a good thing. So when they do relapse, chances are there will be a new option for this patient. But a CLL cure still remains elusive. So, Dr. Jacobs, if you can speak to…we’ll just jump right into some of the newer, the novel therapies and things that are being investigated with CLL treatment. If you can just speak to some of those newer therapies, the novel pathways and targets that are currently under investigation with CLL, we’d appreciate that.

Dr. Ryan Jacobs:

Sure. We’ve come a long way in how we are managing this common cancer that’s benefiting a lot of patients. And as mentioned, with this cancer being one that is more common in the older population, we do know that the population of the United States specifically is getting older, there’s going to be more 70-year-olds. So these breakthroughs are helping a growing number of CLL patients.

Before 2014, really outside of a clinical trial, the only way we could treat CLL Is with combinations of chemotherapy and an immune therapy, like a monoclonal antibody called Rituximab, that was kind of our first, what we would call targeted treatment outside of chemotherapy that we had, and it was, like targeted treatments are, well tolerated.  It was an antibody that targets B cells specifically. So we were combining it with chemo, we would call that chemoimmunotherapy, and it helped a lot of CLL patients. But for many, those were poor prognostic markers in particular, and those with relapse disease, chemotherapy was not very helpful, and it was quite toxic in many circumstances. So we’ve been fortunate that since 2014, we’ve had a lot of new treatment options, and they’re targeted therapies. It’s not like non-specific cytotoxic chemotherapy, these are treatments that have been developed with specific targets in mind that are unique to the B-cell neoplasm, the B cell cancer, the CLL.

And the first of these that really changed everything was a BTK inhibitor called ibrutinib, that we got in 2014. Initially, we can only use it in the relapse setting, but eventually, in 2016, we could start treating patients as a first line of therapy with ibrutinib (Imbruvica). And then in 2019, we had a newer version of BTK inhibitor, we call those second-generation BTK inhibitors. That drug was acalabrutinib (Calquence). And it eventually was shown in a head-to-head study to be just as effective as ibrutinib in a relapsed patient population, but it had less side effects than ibrutinib. So in specifically, atrial fibrillation, hypertension. Cardiac toxicities overall were one that they really focused on in that study. So as a whole, when we were choosing BTK inhibitors, we were shifting away from ibrutinib, shifting to acalabrutinib, and then just as…earlier this year, we had a third BTK inhibitor, zanubrutinib (Brukinsa), that was approved. It’s also considered a second-generation BTK inhibitor like ibrutinib and acalabrutinib.

It treats CLL in the same way, in how it inhibits BTK or Bruton’s tyrosine kinase, that’s overexpressed in CLL cells. But it also has a favorable toxicity profile when compared head to head with ibrutinib, and now we have two second generation options between a acalabrutinib and zanubrutinib. And it’s not really easy for us to know between those two, which is “better.” When we decide to treat with a BTK inhibitor, we’re usually choosing between those two at this point, and we’re trying to personalize the decision for the patient, and there’s some different factors they can get involved in that complicated decision. Luckily, we are not limited to BTK as a target. I mentioned earlier, we have monoclonal antibody, rituximab (Rituxan) like the one I mentioned, but a newer version of Rituximab, a more potent version, obinutuzumab (Gazyva). Is one that we have available along with a Bcl-2 inhibitor, venetoclax. That is now, as of 2018, improved in the frontline CLL setting, also approved in the relapse setting, of course, since 2016.

And we use venetoclax with a monoclonal antibody like obinutuzumab, and together they are a very potent combination that cause pretty rapid cancer cell death, as opposed to the BTK inhibitors that more put the cancer to sleep and require daily dosing indefinitely for as long as the drugs work. And remarkably, the data on BTK inhibitors tells us that should work for many, many years. They’ve been following some of the patients that got treatment in the first line setting, and eight years out, there’s still more than 50 percent of the patients are free of progression, so they can’t even quote an average response time yet. With eight years of follow-up on the early ibrutinib patients. The difference with venetoclax combined with a monoclonal antibody like obinutuzumab, is because it causes a more rapid cell death, you can give it on a time-defined schedule. So we tend to give it for one year in the first-line setting and two years in the relapse setting, and the antibody portion is just given for the first six months.

The BTK inhibitors and venetoclax are oral treatments, so that’s a big win for patients to avoid the infusion center for those treatments, but the IV antibody treatments will still require some trips to the infusion center if you’re doing that combination with venetoclax. For most patients, those two targets are what we’re choosing between, and we try to personalize the decision to the patient. And again, that’s a very complicated discussion on what is “best”. And we use things like the prognostic work-up, medical problems that the patients already have, medicines that patients are on, to help make the best treatment decision for our CLL patients. But those…for in terms of how well that treats the CLL, both of those are considered equivalent options for the large majority of CLL patients. We’ve got some things on the horizon, but in general, those are two targets that we have at this point. There is for relapsed patients, PI3 kinase inhibitors that are still FDA approved at this time, that aren’t quite as effective and more toxic, so we sometimes think about using one of those targeted therapies if a patient has already progressed on a BTK inhibitor in venetoclax class.

In the future, we are looking towards combining BTK and Bcl-2 inhibitor. Like for example, there’s been studies already done that I’ve put many patients on, with ibrutinib-venetoclax, and I believe there’s a question about that later. There’s also an ongoing study that I have opened at my institution that’s looking at acalabrutinib and venetoclax. So taking these two pills together in a time-defined manner, so you don’t have to take the BTK inhibitor indefinitely. And then there’s some therapies that have already been improved in other lymphomas, and we wonder if they’re going to have a role in CLL eventually. So we now have bispecific antibodies, so that’s taking a drug like Rituximab or obinutuzumab and adding a T-cell engager to it so it has two targets or it’s bispecific. And we have that drug, mosunetuzumab (Lunsumio) available in follicular lymphoma, and there are several others in development, and we’ll see how their role comes into play in CLL as well. As well as CAR T-cell therapy, where we take a patient’s T cells and genetically engineer them to attack the cancer. That’s now an approved therapy for many different kinds of lymphomas and multiple myeloma as well. So we wonder if that’s going to have a role in CLL.

But I think for the foreseeable future, it’s going to be looking first at BTK and then Bcl-2 inhibition, or vice versa. And we don’t really know which is better to go first, we think they’re both…they can both be sequenced one after the other. And then maybe it will have some of these other breakthroughs coming in and helping for after patients need something beyond those therapies. And there’s probably going to be a lot of patients that never need anything beyond those options, those initial couple of targets, because they do so well. I think in the most immediate future, the approval that is going to give us a new great option is going to be for an alternative site BTK inhibitor, or it’s also called a non-covalent BTK inhibitor.

And there’s this drug called pirtobrutinib, it has been approved in mantle cell lymphoma and likely will get approved in CLL this year. And that drug specifically is a BTK inhibitor that still works even in patients that have, say, progressed on ibrutinib or acalabrutinib or zanubrutinib. That will be a new target available for CLL patients and probably pretty quickly become one of the go-to drugs that we use for relapsed CLL patients that have already been treated with a BTK…with a traditional BTK inhibitor. So growing number of options and it’s really great for our CLL patients.

Lisa Hatfield:

Thank you for that overview again, Dr. Jacobs. It does sound like there are a lot of new therapies coming out, especially for relapsed patients, super exciting for them. And this is actually a great time to jump right into questions. We have many questions from patients that different patients have submitted. But first, I want to remind everybody that this program is not a substitute for medical care. Please consult with your medical team for advice on your own condition or disease. And, Dr. Jacob, I was taking notes as you were talking, because you had spoken a little bit about a combination of the BTK inhibitor and Bcl-2 inhibitor with venetoclax. And I did a little research last night before I talked with you, and it sounds like that is something that the CAPTIVATE trial is investigating. 

So that’s exciting, and a patient asked about that, what that trial is. And it’s music to my ears as a cancer patient to hear something like “fixed duration,” it’s also investigating a fixed duration so patients and have maybe a bit of a medication vacation. So can you speak to that trial a little bit and explain what it is a little bit on how that might benefit patients with CLL?

Dr. Ryan Jacobs:

Yeah. So one of the best elements of treating with venetoclax is that it produces a deep level of remission in many patients. In fact, when given with the monoclonal antibody obinutuzumab, to CLL patients receiving that treatment as a first line of therapy for their CLL, about three-quarters of CLL patients will get to so deep of a remission that we call them minimal residual disease-negative. And that’s a blood test or a bone marrow test, but more easily done as a blood test, where we can look to a sensitivity of one in 10,000 white cells and determine if there’s any CLL in those 10,000 cells. We can actually go deeper than that, but we say, we call patients negative if they’re less than one in 10,000. And so 75 percent of patients will get to that depth of remission just with obinutuzumab for six months along with venetoclax for a year. So when researchers saw that, they recognized that we could probably stop treatment in those patients getting venetoclax because venetoclax yields these deep responses. And then the next kind of thought was, well, could we give a BTK inhibitor with venetoclax, but also over a defined treatment timeline and maybe get some of the remarkable benefits of treating with a BTK inhibitor but not get stuck being on therapy for years and years.

So the CAPTIVATE study was the first really to, in a large Phase II manner, look at that combination in a younger patient population, it was for patients 70 and younger. And it wasn’t in a high risk or anything, it was all comers. But they did have to be 70 and younger and getting treatment as a first-line therapy. So the combination was very effective. As of the last American Society of Hematology meeting in December, four years of data was reported and a large percentage of patients were still free of progression, over 80 percent still free of progression. And that’s three years off therapy at that point.

It was well-tolerated, not many patients had to come off due to toxicity. It was, in fact, less than 10 percent had really significant toxicities requiring discontinuation. So it was a well-tolerated effective treatment.

I do have one of those studies to open at my institution, the acalabrutinib-venetoclax combination, it’s called the MAJIC trial, and it is a large Phase III study that if it’s successful, I think would lead to the approval of giving those two drugs together. But then the extra credit question is, who should get the combination and who should get the drugs separately? And we don’t have an answer for that right now, and that’s a long topic of debate among CLL specialists.

Lisa Hatfield:

Great. Well, thank you. So for that trial you spoke of that you’re conducting right now, is that…is it only relapsed patients who are eligible for that? Or is that for front-line therapy?

Dr. Ryan Jacobs:

No, this is a first-line therapy that the MAJIC study is.

Lisa Hatifield:

Oh good. That’s promising for patients too.

Dr. Ryan Jacobs:

And it has a really good comparator arm, so that won’t be a problem that the standard arm on that study is venetoclax plus obinutuzumab, so it’s comparing against one of our best treatments, and so we really will get the answer of does it look better to use the BTK with the Bcl-2? Or is it not really that much better than just giving an venetoclax with obinutuzumab? And then the one obvious element that I didn’t mention that would be nice for most patients in addition to being efficacious and well-tolerated is if you could get an all-oral combination. Of course, venetoclax with obinutuzumab, you’re still getting quite a few infusions with the obinutuzumab over the first six months. So that’s a lot of time in the infusion center that you could avoid with just the combination of two oral targeted agents. So that would be a breakthrough for patients too, I think.

Lisa Hatfield:

Well, you commented also on something that’s really important for patients to know, and that is that if you go into a clinical trial, you won’t be given nothing for cancer clinical trials, you’re going to be given the standard of care or whatever it’s being compared to. So for patients who are considering that.

Dr. Ryan Jacobs:

That’s a Phase III. Yeah, for Phase III. If you go on an earlier phase trial, you know exactly what you’re getting. There’s usually not any randomization for earlier phase studies, you just get the intended treatment.

Lisa Hatfield:

Okay, great. Well, thank you so much for explaining that. So we have some pretty specific questions, and we have a patient who wrote in and asked, “What is the difference between IGHV-mutated and IGHV-unmutated CLL? And can you talk about treatment considerations for those?”

Dr. Ryan Jacobs:

Yeah. So that’s part of a bigger discussion around the prognostic work-up of CLL and not all CLL is the same, and we’ve done a really good job of figuring out tests to separate out the CLL patients that tend to behave more aggressively and respond to certain kind of therapies, versus those that are more of what we call indolent or slow growing and respond to other kinds of therapies. I do want to say, I haven’t mentioned it yet, we still don’t treat CLL if it’s not causing any problems. And about half of patients get diagnosed as sort of an accident, and they get a blood test for something else, and their white count is elevated, and that leads to a diagnosis, but they feel fine. We still leave those patients alone. Even with these good treatment options we have, we recognize that there are a select percentage of CLL patients that don’t ever need treatment, and so we don’t just want to start treatment in everybody.

But I do still like to check this prognostic work-up, even if I’m not going to start treatment, but I make sure and ask the patient if that’s what…iIn line with what they want. But certainly, if you’re going to start treatment, you’re required by guidelines to check a prognostic work-up, and I would really encourage the CLL patients tuning in to ask their oncologist, “What is my prognostic work-up?” if they’re going to start treatment.  Because of the oncologists, unfortunately, that have to deal with lots of other cancers, maybe don’t always know the right test to send. I’m very spoiled in that I get to just treat lymphoma and specifically focus a lot of my research in CLL and get to stay up with all this. I don’t know how a general oncologist keeps up with everything, honestly.

But the big three tests are going to be the FISH analysis, fluorescence in situ hybridization. And then IGHV mutational analysis, and then also a TP53 mutation analysis. And I don’t really have time to go through all of those, but IGHV is the question I get a lot. “What is that?” It’s one of these rare findings where it’s actually normal to have a mutation at the IGHV. IGHV stands for immune globulin heavy chain variable region, and it is usually mutated in B lymphocytes because it’s part of the process of a mature lymphocyte that is able to make a lot of different kinds of antibodies. And it undergoes somatic hypermutation, is what it’s called, as the B cell matures. Generally in oncology, the more mature a cancer is, the less aggressive it behaves and usually the easier it is to manage, and that is the case with CLL. So think of an unmutated IGHV CLL cancer as a more primitive or a more immature cancer clone, and as such, it is harder to treat.

In about half of patients will be found to be unmuted at the IGHV and historically, all we had was chemo and we knew these patients weren’t going to respond for near as long as the IGHV-mutated patients were to chemo. What’s nice is, with our targeted treatments, particularly the long-term data with the BTK inhibitors, it doesn’t look like it matters whether you’re mutated or you’re unmutated. So that’s one of the really great things with our new treatments for CLL, is it has, the people that have benefited the most are the ones that were doing the worst, so that’s great. It’s not just the patients that were already doing well, that are doing even better.

Lisa Hatfield:

So I just want to take a step back and kind of looking at this through the lens of a newly diagnosed CLL patient. You’d mention that sometimes you don’t treat every CLL patient. So is there something, if you find a patient who does not need treatment, is there something you tell the patients as far as regular monitoring? Will you monitor them to see if it progresses to the point where it requires treatment?

Dr. Ryan Jacobs:

Yeah. And we’re fortunate that this is a blood cancer that most of the time we can follow with a simple blood count and follow the white count, follow how the…follow the health of the bone marrow by looking at things like anemia, low red cell count, or a low platelet count that we call thrombocytopenia. So that’s the easiest thing to follow, but I’m also talking with my patients and examining my patients. I want to know if their length nodes are causing them a lot of pain, because we should treat that, there’s no reason they should live in pain.I want to know if they’re waking up drenched in sweat all the time, if their quality of life has been really affected by that. Or are a dramatic amount of fatigue that we can’t explain by some other cause. And I also, of course, examine the nodes myself and make sure that there’s no alarming findings there. So that’s really what’s involved with checking on a CLL patient that’s on active surveillance, that’s what we call it. And there’s a list of criteria that the oncologist should know in terms of deeming who needs treatment and who doesn’t. And so we’re kind of following the same rules, so to speak, in terms of who gets treated for CLL.

Lisa Hatfield:

Okay, thank you. So we have a patient who asked a series of questions here, and I think you already…you spoke pretty well to the role of the BTK inhibitors in treating CLL. I’m going to kind of clump these together.  So I guess three questions. What treatments do you think are the most beneficial for patients whose CLL has relapsed? What are the poor prognostic indicators for CLL? And along the same lines, what are the high-risk genetic markers for CLL?

Dr. Ryan Jacobs:

It’s a little more complicated discussion in the first line setting because both are options. At this point in time, we haven’t been…at least those that are, I would say, staying up to date on the CLL data, we have not been using chemotherapy for a long time. So most of the relapsed patients will have seen either one of the BTK inhibitors or venetoclax. And so what we do in the second-line setting is just use the other option that they haven’t seen. The data tells us, when you look at what treatments are being prescribed, most patients are going on BTK inhibitors, and they have been around longer than venetoclax in general. So for a lot of patients, that relapsed treatment is going to be venetoclax. Because that has the best data in terms of treating patients that have progressed on a BTK inhibitor like ibrutinib or acalabrutinib or zanubrutinib.

In the near future, we’ll have pirtobrutinib (Jaypirca) and so maybe, maybe some will get that drug before venetoclax, and that’s probably okay. And so we’ll have that additional option. The complicated patients, and I’ve alluded to this, or what do we do after BTK and Bcl-2? What are we left with? I mentioned PI3 kinase, that’s not a great option. There’s still stem cell transplant out there for young patients that are running out of options. Clinical trial is really what I would like to emphasize there.  If you’re a patient that can get to a high volume referral cancer center with a CLL specialist, I would do that. If you have seen BTK inhibitor and venetoclax and are looking for other options.

Lisa Hatfield:  

Great, thank you. So the next question is actually a really good question, I think we can broaden it a little bit. But the question is, “How can I ask my doctor to make sure I am being tested for serum markers?” And more broadly, I think a lot of patients are a little bit nervous about asking questions of their doctor, because they don’t want to feel like they’re questioning their expertise or doubting them. So how in general can we ask our doctor questions if we hear something? Or how we approach our doctor with those types of questions?

Dr. Ryan Jacobs:

So I mentioned asking your doctor, “What’s my prognostic markers?” I think this is probably the easiest way to get that information. And your doctor should be checking those. The question comes up like, what are the “high-risk” markers? We talked about mutated versus unmutated. Thankfully, our novel treatments that doesn’t seem to matter. Same goes with…there’s on FISH there used to be, if you found three copies of chromosome 12, that’s called trisomy 12, that doesn’t seem to matter With our newer treatments. A deletion at chromosome 11, again, used to not do as well with chemo. Novel therapies…doesn’t seem to matter. The one that is still potentially affecting outcomes, even with our novel treatments, are chromosome 17 aberrations, which stately are rare in the initial diagnostic setting. That or a TP53. A deletion at 17p or TP53 mutation probably is only going to be around 10 percent of patients or so. And in the relapse setting though, that number goes up because of the more aggressive cancers emerge, we call that clonal evolution. So maybe in the 20-ish percent range. These patients, we tend to prioritize indefinite therapies first, because it seems like these patients do better if you keep treatment going, as opposed to interrupted therapies like venetoclax. And so we tend to treat those patients with a drug like acalabrutinib or zanubrutinib first and then think about the venetoclax later for those patients.

Lisa Hatfield:

Okay. Okay. And just to clarify, for patients too, I know that a lot of cancers, there are discussions about the 17 deletion, 17p, and then also the TP53 gene. So if I understand correctly, the TP53 gene is housed on chromosome number 17. So if that is missing, then that patient may be missing that gene, that is considered a tumor suppressor gene, which we want. Is that correct?

Dr. Ryan Jacobs:

Right. So it’s either missing, which is what we see on FISH with a deletion, or it can be mutated and that’s the next gen sequencing, and often it will be both in those patients.

We think with indefinite, there’s some really good data that was just released with zanubrutinib. When they looked at 17p-deleted patients, there’s some long-term follow-up with ibrutinib-treated 17p-deleted patients. With chemo these patients would only get about a year or so, but we’re getting maybe even close to normal outcomes with long-term BTK. But we do know if you just give them a year of venetoclax and obinutuzumab for six months and then stop, they do relapse quicker than the other patients. So they relapse after about four years. As opposed to with five years of follow-up with that first line venetoclax approach, there are 62 percent of patients are still free of progression.

Lisa Hatfield:

Oh wow, okay. Thanks for explaining that too. I know that that chromosome 17 and the TP53 gene, that’s talked about in a lot of different cancers and it often come up, “How are those connected?” So thanks for just describing that a bit. So this patient is asking, “For patients who may be eligible for BTK inhibitors, are there specific comorbidities that might contribute to adverse side effects?”

Dr. Ryan Jacobs:

Yeah, so we screen…all BTK inhibitors have some cardiac toxicity. They have been shown with the second-generation BTK inhibitors to have less cardiac toxicity than ibrutinib, specifically atrial fibrillation. So if you have atrial fibrillation, maybe that’s a reason why you might go on venetoclax first as opposed to a BTK inhibitor. But it’s not a contraindication to getting a BTK inhibitor if the atrial fibrillation is under good control.  Other cardiac risk factors would include difficult to control hypertension at baseline, or heart failure. These are all things that might make us think twice about using a BTK inhibitor as our first therapy, because venetoclax has no cardiac toxicities. The other thing to consider is BTK inhibitors all to a degree have, and I describe it to patients, like an aspirin-like effect on the platelets. They do interfere with the platelet binding, which so universally, patients will know to varying levels some easier bruising.

And if patients are on, because of say, they’ve had a heart attack in the past and they’re on aspirin at baseline, or what would even be more concerning if they were on a drug like Plavix because they’ve had a stent placed, that would be something that would really concern me and would definitely push me more towards venetoclax, that again, doesn’t have those anti-platelet interactions. Also, patients who are on blood thinners because of a history of blood clot or atrial fibrillation, there is the potential increased risk for bleeding and bruising there as well. None of these are absolute contraindications, they’re just all what goes into the blender, if you will, of putting lots of information in and coming up with the best treatment decision as personalized for the CLL patient. We’re blessed to have multiple options, but it does make it more of a challenge to find the “best” option.

Lisa Hatfield:

Yeah. Thank you for that. We have several questions from a couple of patients regarding side effects. So the question, “How long will my side effects of my CLL treatment last? And what can be done to reduce those?” And specifically, a patient is asking if there’s a connection with CLL and gastrointestinal issues?

Dr. Ryan Jacobs:

So all of the treatments, including venetoclax, the BTK inhibitors, will have diarrhea listed as a possible side effect. It’s usually low grade. But generally, I have found the gastrointestinal toxicities abate some over time. So if they are present earlier, if you’re able to stick with therapy, they do tend to get better. For the once daily meds, I encourage those patients to try to take the drug in the evening. The GI tract tends to be less active later in the day, and you can sleep off some of the potential gastrointestinal issues. So I’ve had success there. Sometimes we have to lower the dose to just find the best dose to help mitigate some of these. There’s the antidiarrheals that can help if you need them. Imodium. I had a patient I saw earlier this week that Imodium didn’t really work, but good old Pepto Bismol did the trick from time to time. So certainly though, if the gastrointestinal issues are significantly affecting quality of life, we need to come up with a new plan, whether that’s reducing the dose or changing to a different option. Specifically, what’s nice about the BTK inhibitors is they all have data that show if you’re having problems with one, you can switch to the other and likely not have the same problem occur. So that’s nice.

Lisa Hatfield:

Have you ever seen any uncharacteristic side effects several times in your practice? Anything really unique? I’m just curious about that.

Dr. Ryan Jacobs:

Yeah. There’s always the patients, they can have a more severe form of maybe, of a more common side effect, like the…we were talking about diarrhea, I’ve had a patient that actually had a difficult, with venetoclax, had difficulties with the stool incontinence. So that was kind of a severe form of that. It wasn’t so much diarrhea that was the problem. But we were able to ultimately mitigate that with a dose reduction. I would say the way, particularly if it’s an unusual side effect, the best thing to do is to take a break. If it’s a serious side effect that needs to be addressed and it’s affecting quality of life or causing problems, take a break from the treatment. If you take a week off these treatments, particularly venetoclax, taking breaks doesn’t matter. We like not to take long breaks with the BTK inhibitors. But if you take a week off, these drugs don’t have very long half-lives. So if the issue is not getting any better and you’ve been off of treatment for a week, it’s unlikely that that issue is coming from the treatment. So that’s a way I try to sort through some…particularly if they’re unusual side effects sometimes. And certainly, if we deem that the issue is connected to the treatment, I’ll usually try lowering the dose before just giving up.

Lisa Hatfield:

Okay. Thank you. A patient had asked, and I love this question because I often wonder myself when I get up in the morning, my bones are creaking and popping, “How do you know the difference between,” this patient’s talking about fatigue. How does a patient discern, “Well, this is fatigue from my cancer or my treatment,” versus just normal aging? Whether it’s fatigue or bruising or any side effect.

Dr. Ryan Jacobs:  

Yeah. Fatigue is a really…I had an attending physician when I was in my training that said, “Treating fatigue makes me fatigued.” But it’s hard. If it’s really the only problem the CLL patient is having, it can be. All those other problems I had mentioned earlier, the low red cells, the low platelets, the painful nodes, the night sweats, I with close to 100 percent certainty know I can fix those with treatment.Fatigue, I’m not as confident when that’s the only issue that a patient’s having. I try to differentiate between fatigue from other causes and old age, and specifically to CLL. 

They try to put it as a metric and say, if you’re having to spend half the day or more just lying around and you’re not able to do your normal activities of daily living, like that’s a severe level of fatigue and treatment should be considered.I’m looking for somewhat of a precipitous decline, not necessarily just kind of the gradual fatigue that you might more relate to aging. The problem with treating fatigue is you’ll look, if you look at the possible side effects of all of these medicines I talked about, fatigue will be a potential side effect.So you’re sometimes trading one problem and getting another, or maybe the fatigue does get better, but then the patient has some different side effect that’s even worse than the fatigue. So it’s hard to really help when fatigue’s the only issue. But certainly, I have helped some patients with fatigue. We don’t have a test that we can do to know for sure is the fatigue coming from the cancer, or is it coming from something else. 

Lisa Hatfield:

Great. Well, that wraps up our program for today. Thank you so much for joining us, Dr. Jacobs.  I am Lisa Hatfield from Patient Empowerment Network.


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Top Two Reasons Why CLL Patients Should Participate in a Clinical Trial

Why exactly should a chronic lymphocytic leukemia (CLL) patient think about joining a clinical trial? In In the “Why Should CLL Patients Consider a Clinical Trial?” program, expert Dr. Adam Kittai from The Ohio State University Comprehensive Cancer Center – The James explains the motivation of clinical trials and the benefits CLL patients may receive from clinical trials. 

1. Improve Future CLL Treatments

Clinical trials examine the benefits of a specific treatment for a specific cancer and cancer stage. If you or your loved one participates in a clinical trial, there can be a double benefit to participation. The data gathered from clinical trials assists researchers in improving future CLL treatments for the patient who participates in addition to other CLL patients. Clinical trials can often have underrepresentation by BlPOC patient groups, and it is important for these groups to be represented in trials in order to develop the most refined treatments for all patient races, ethnicities, and genders.

2. Gain Access to Unavailable Therapies

In addition to improved treatments, clinical trial participation has other patient benefits as well. If you or a loved one participates in a clinical trial, the patient gains access to treatments or therapies that may not be accessible in another way. Clinical trials sometimes use different combinations of treatments that haven’t been used previously for a specific stage or type of cancer. Or clinical trials may offer access to a cutting-edge therapy that may ultimately be both more effective while also causing fewer side effects, which could result in a major win-win for patients.

By participating in CLL clinical trials, patients can help improve future CLL treatments for themselves as well as for others. If you have additional questions about clinical trials, ask your doctor or other healthcare provider. If they don’t have information about trials for your specific cancer and stage, they can check with specialists who would more familiarity. You can also find a database of clinical trials at clinicaltrials.gov.

Developing CLL Research and Treatment News

Developing CLL Research and Treatment News from Patient Empowerment Network on Vimeo.

CLL expert Dr. Michael Choi provides his perspective on the goals of current CLL clinical trials, discusses approved inhibitor treatments, and shares credible resources to keep up with the latest news in research.

Dr. Michael Choi is a hematologist and medical oncologist at UC San Diego Moores Cancer Center. Learn more about Dr. Choi. 

See More from CLL Clinical Trials 201

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Hesitant to Participate in a CLL Clinical Trial? What You Should Know

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Transcript:

Laura Beth:

Dr. Choi, are there recent advances in CLL treatment and research that you are excited about?  

Dr. Choi:

There’s certainly a lot to be excited about as far as new treatments or new understanding of our treatments. What I see as kind of two main aims of trials right now for our patients with CLL, one is to figure out the optimal way to treat patients, especially in the first line of treatment.  

For the past few years, we’ve had two very clear options, two very clear standards, a BTK inhibitor or the combination of venetoclax and a CD20 antibody. And so, right now, there are a couple of trials both in the states and internationally that are for the first time really comparing those head-to-head. At UCSD, we’re eagerly hoping to join one of those trials as well, and so this will help us and help our patients kind of really know which of those options make the most sense for maybe different subgroups of patients.  

I guess the other main emphasis is to have new therapies available to patients in case these existing standards stop working. And fortunately, this is not a common occurrence. Resistance to BTK inhibitors and Bcl-2 inhibitors is not common, fortunately. But we have to be ready with something if that does occur for our patients.  

Certainly, there’s a lot of enthusiasm for the next generation of BTK inhibitors, cellular therapies like CAR-T therapy, and other classes of medications. So, while I hope most of my patients never need those drugs or never need those trials, I think it’s important that we have those available.  

Laura Beth:

How can patients keep up to date on developing CLL research?  

Dr. Choi:

Oh, that’s a great question. I guess I sometimes ask that same question of myself. How can I stay updated on all the developments and discoveries. Yeah, I guess, yeah, certainly talking to your doctors about what other options there may be. Sometimes, that’s maybe the simplest question to ask.

Yeah, I wish online things were a little bit more straightforward. When I go onto clinicaltrials.gov, I pull up hundreds of different CLL trials, some that might not be relevant for all of my patients. I think The Leukemia & Lymphoma Society and other societies and your group as well have done a great job communicating what some of the most promising areas of research are.  

Hesitant to Participate in a CLL Clinical Trial? What You Should Know.

Hesitant to Participate in a CLL Clinical Trial? What You Should Know. from Patient Empowerment Network on Vimeo.

What should patients know about clinical trials? CLL expert Dr. Michael Choi explains patient trial opportunities and provides key questions to ask about clinical trial participation.

Dr. Michael Choi is a hematologist and medical oncologist at UC San Diego Moores Cancer Center. Learn more about Dr. Choi. 

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Transcript:

Laura Beth:

Dr. Choi, what would you say to someone who is perhaps a little hesitant to participate in a trial to encourage them to learn more?  

Dr. Choi:

Yeah, certainly, it’s very natural to be anxious and to be hesitant about entering into a clinical trial about volunteering to receive something that maybe hasn’t been fully tested before. You know, I think when I talk to my patients about trials, one thing I try to keep in mind is that ultimately, to a degree, to a large degree, we have our trials for our patients. We want to have our trials open at our center so that patients that can benefit from them can have access to them.  

And so, a lot of trials are really kind of designed in that way, to give patients a chance at something that we think will be better or a chance to get a drug when other drugs have stopped working. So, I think many clinical trials aren’t really with the thought that we want to prioritize the science and that our patients are just guinea pigs.  

In fact, I think all of us that are treating patients with CLL and being a part of CLL clinical trials, I think we’re really doing our best to prioritize our patients and their health. The trials are really just a part of that. But beyond that, I think maybe the questions that can be asked would be kind of what’s known already about these drugs. 

 Many trials are using drugs that we’ve already used for many years and maybe just using them in a different manner. So, talk to your doctors about what’s already known. Certainly, the question about how will they be monitored, that’s an important question for your team too. And then, certainly, make sure you understand if there are any other options that would be appropriate or good for you and discuss the pros and cons of the trial versus those options. 

How Does Patient Clinical Trial Participation Move CLL Research Forward?

How Does Patient Clinical Trial Participation Move CLL Research Forward? from Patient Empowerment Network on Vimeo.

Chronic lymphocytic leukemia (CLL) expert Dr. Michael Choi shares how clinical trial participation helps advance research and benefit the CLL community.

Dr. Michael Choi is a hematologist and medical oncologist at UC San Diego Moores Cancer Center. Learn more about Dr. Choi. 

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Transcript:

Laura Beth:

Dr. Choi, why is patient participation in CLL clinical trials so critical to advancing research?  

Dr. Choi:

Yeah, there’s still so much that we can do better for our patients. We’ve come a long way. I think we have a few – many treatments that we can really count on to work when we need it, but I think we still have a way that we can refine this more, which combination to use, which sequence to use, how long to do the certain treatments, and then, of course, what to do if those treatments stop working.  

So, I think, yeah, trials help us answer these questions in kind of formal manners so that the information can be used to help other patients in the future.   

Laura Beth:

I imagine that trial participation benefits the CLL community as a whole, by helping to move the research forward?   

Dr. Choi:

That’s so right, yeah. I’m always humbled and impressed by, I guess, the selflessness and the bravery of some of our patients, or of all of our patients and their families and their loved ones. Volunteering for a trial is certainly no trivial thing, not a trivial thing. And so, yeah, I think that that realization that by being a part of a trial, they’re not only potentially helping themselves and getting good care but also helping the future patients as well.  

How Is a Patient’s Safety Monitored in a CLL Clinical Trial?

How Is a Patient’s Safety Monitored in a CLL Clinical Trial? from Patient Empowerment Network on Vimeo.

CLL clinical trials have safety protocols, but how are they carried out? CLL expert Dr. Michael Choi explains the frequency of monitoring, what happens if adverse events occur, and the groups that oversee clinical trial safety.

Dr. Michael Choi is a hematologist and medical oncologist at UC San Diego Moores Cancer Center. Learn more about Dr. Choi. 

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Are CLL Clinical Trials Safe?

Hesitant to Participate in a CLL Clinical Trial_ What You Should Know

A CLL Expert Addresses Common Clinical Trial Misconceptions

Transcript:

Laura Beth:

Dr. Choi, a lot of patients worry about the safety of a clinical trial. They wonder, “Is it safe, or am I going to be a guinea pig?” What is done to help ensure safety for patients when they’re in a clinical trial? 

Dr. Choi:

Yeah, certainly every clinical trial brings with it or introduces some sense of uncertainty.  

After all, that’s why the trial is being done, because we are trying to learn about how effective or how safe or how tolerable a drug or drug combination is. But certainly, trials are designed in a way that prioritize or emphasize the safety and the monitoring of patients. Oftentimes, trials will have very clear guidance on how often a patient will be assessed, sometimes have very clear recommendations about what to do about each individual lab abnormality that may come up, and certainly very clear guidance on how to adjust the dose of the drugs that are being used if there’s any sort of toxicity.  

But yeah, certainly, I can empathize with the concern that something that’s very new, we may be learning at the same time as our patients as far as what side effects may come up.  

But I do want to emphasize that oftentimes, these aren’t total unknowns, that the research that goes into it, a drug or a pathway, even before the trial starts, gives people a good sense of what things to watch for and how safe things may be.  

Laura Beth:

Is there an oversight committee or a safety committee that reviews the safety information of a clinical trial?  

Dr. Choi:

That’s correct, yeah. Behind the scenes, there are, I imagine, kind of armies of people that are eagerly refreshing their screens to see results come in, both out of excitement to see how something is working, but also to make sure that we’re on top of any side effects or any toxicities that may affect other patients on the trial. Very rarely, maybe a patient on one part of the continent has some side effect, and that information is very quickly and formally disseminated to all the other sites.  

Sometimes, that leads to the other sites deciding to halt their enrollment to figure out what happened and prevent it from happening again, or at the very least, know to keep track of that in our other patients as well. So, yeah, definitely people monitoring things and really, with the priority of keeping other patients safe or keeping all patients safe.  

How Are CLL Patients Monitored After a Clinical Trial Concludes?

How Are CLL Patients Monitored After a Clinical Trial Concludes? from Patient Empowerment Network on Vimeo.

What happens after a clinical trial is complete? CLL expert Dr. Michael Choi explains how participants are monitored during clinical trial follow-up.

Dr. Michael Choi is a hematologist and medical oncologist at UC San Diego Moores Cancer Center. More information on Dr. Choi here. 

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Transcript:

Laura Beth:

Is there follow-up that’s done after a trial concludes? 

Dr. Choi:

Oh, good question. Yeah.  

Yeah, trials are kind of – let me say what – yeah, when a patient goes through a trial, there can be a sense that the trial concludes, perhaps when the treatment is done or at a certain point when a response assessment is made, but oftentimes, it’s important to also continue to monitor patients after those milestones.

Certainly, for some of our drugs, the treatment continues long-term, so even after some statement has been made about a response rate, many patients remain on treatment, and it’s certainly important to see if there are any long-term side effects or any other developments after the end of that initial period.  

 Other treatments, the trial – the treatment may end. An example might be these trials that combine BTK inhibitors and Bcl-2 inhibitors that are typically for a year-and-a-half or so.   

And certainly, for those trials, it’s definitely critical for patients to be followed as part of the trial so that we can get a good sense of how long those remissions are lasting. Also, of course, to see if there are any delayed or long-term toxicities. So, yeah, so oftentimes, being a part of a trial means being followed, being monitored for some time afterwards.  

What Happens in Each Phase of a CLL Clinical Trial?

What Happens in Each Phase of a CLL Clinical Trial? from Patient Empowerment Network on Vimeo.

What are the phases of clinical trials? CLL expert Dr. Michael Choi outlines the research purpose of clinical trials and what happens in each phase.

Dr. Michael Choi is a hematologist and medical oncologist at UC San Diego Moores Cancer Center. More information on Dr. Choi here. 

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Transcript:

Laura Beth:

Dr. Choi, can you please walk us through the phases of a clinical trial and what happens during each phase?  

Dr. Choi:

That’s a great question. Yeah, historically, trials have been divided into different phases. The way I think of it is when a drug is first being tested, we don’t want to expose too many people to it, because we’re still learning about the right dose and about its safety. And then, as we learn more and more and maybe get some confirmation that it’s doing what it’s supposed to do, then we have bigger trials and eventually, bring in some comparisons to existing standards.  

So, a Phase I trial is usually, I would say, a few dozen patients, getting the drug for the very first time or sometimes for the first time for this diagnosis. Oftentimes, the very first Phase I trials might have a dose escalation component where the first dose or the first group of patients might get a dose that is based on an assurance that it will be – or some confidence that it will be safe and well-tolerated.  

Then, as the trial goes on, a higher dose will be used once we see that the previous doses are safe. Now, sometimes, this dose escalation happens in between different groups of patients, and sometimes, some trials will escalate the dose for even within an individual patient. But the basic idea of it is to start at doses that we think will be safe and then to gradually escalate it, again, prioritizing the safety of the patients.  

I shouldn’t also – although Phase I trials are designed to determine the safety of a drug, there are many Phase I trials that show clinical activity and benefit to the patients, so I don’t think people should be altogether discouraged from enrolling in a Phase I trial either. 

I can also say that some Phase I trials are just looking at a combination of drugs that we have experience with already, but designed or written as a Phase I trial, because we have to confirm the safety of those two drugs. In those trials, the doses might not be that different than what’s used already, and there’s often more expectation of immediate clinical benefit. Phase II trials are where we’re principally looking or usually looking mainly at the response rate or some sort of clinical endpoint, how many patients get into a partial remission, or how many patients get into a complete remission and so on.  

And I would say these are usually our trials that are 20, 30, 50 patients, to that effect. And basically, from that group of patients, we can get a pretty good estimate of how effective a drug or a drug combination may be. And then finally, the third type of trial, Phase III trial, is when a new drug or a new combination is compared directly to a different – to what would be considered the standard of care at the time.  

So, this is a way that we can get more confidence that this new drug is indeed better than what we’ve been doing up until now.  

How Could CLL Patients Benefit From Clinical Trial Participation?

How Could CLL Patients Benefit From Clinical Trial Participation? from Patient Empowerment Network on Vimeo.

CLL clinical trials are an option for patients, but what is the benefit of participating in a trial? CLL expert Dr. Michael Choi shares the impact of recent research developments for patients.

Dr. Michael Choi is a hematologist and medical oncologist at UC San Diego Moores Cancer Center. More information on Dr. Choi here.

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Transcript:

Laura Beth:

Dr. Choi, in your opinion, why should a patient with CLL consider participating in a clinical trial?  

Dr. Choi:

This is definitely a time where there has been a lot of recent progress in the treatment of patients with CLL. The drugs that have been developed in the last few years have definitely been advances, have shown that they are both more effective and more safe than the drugs that we had before.  

So, oftentimes, participating in a clinical trial gives our patients access to some very promising therapies before they’re fully available. Certainly, there are some unknowns and still things to learn about these drugs, so one should be – there are safeguards built into these trials, but I’d say the main thing would be getting access to something that may be better than something that we’ve been using in the past. This applies to somebody getting treatment for the very first time where there may be reasons to think that a new drug or a new combination of therapies will have advantages over things that we’ve been using before.  

And certainly, it is relevant to patients where the existing therapies have somehow stopped working where certainly the trials or experimental agents give us or give our patients a chance to get back in remission.  

What Do CLL Patients Need to Know About Clinical Trials?

What Do CLL Patients Need to Know About Clinical Trials? from Patient Empowerment Network on Vimeo.

What is a clinical trial and how does patient participation work? This animated video provides an overview of clinical trials, the process, and details key steps for engaging in your care.

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Transcript:

 Dr. Singh:  

Hi, I’m Dr. Singh, and this is my patient, Elena, who is living with chronic lymphocytic leukemia, also called “CLL.”

And Elena is participating in a CLL clinical trial.  

Let me start by explaining what a clinical trial IS. Basically, it is a research study with human participants. And the goal of cancer clinical trials is to discover new and improved treatments to treat or to prevent cancer. 

At first, when I asked Elena if she would consider participating, she had a few hesitations.  

Elena:

Yes—even though I trust Dr. Singh, I still had questions. 

So, the first thing I asked was, what steps are taken to protect my safety if I participate in a trial? 

Dr. Singh: 

This is a common concern for many patients, and so I explained to Elena that each trial has a strict safety protocol, with set guidelines to protect patients. Beyond that, researchers are required to follow patient safety rules, which are enforced by the U.S Food & Drug Administration (FDA). At each study location, an institutional review board (or IRB) regularly reviews a study, and many trials are overseen by a group called a data and safety monitoring committee. 

And the trial team, which can include nurses and researchers, closely monitors the health of each trial participant regularly, all throughout the process. This is why clinical trials often require more visits and testing, and, in turn, a bigger commitment from that patient.  

Elena: 

After I felt more comfortable about the safety aspects, I asked Dr. Singh which clinical trial he would recommend for my CLL. 

Dr. Singh: 

That’s right. We discussed Elena’s available trial options, reviewed the pros and cons of each approach, as well as the logistics and potential financial impact. 

And it’s important to note that not every patient will qualify for every trial. Clinical trials have “eligibility requirements,” which can vary widely but may include factors like a patient’s age, health, and any prior treatments they have had.  

Elena: 

And there are several phases of clinical trials, right, Dr. Singh? 

Dr. Singh: 

Yes, exactly. The main phases are Phase I, II, III and IV. Each phase gathers valuable information about the treatment and helps measure its effectiveness.  

Elena: 

So, the main reason I joined a trial was to find out if a newer treatment could be more effective than the standard of care to treat my CLL. AND I wanted to help move cancer research forward for the CLL community. 

Dr. Singh: 

Exactly. Not every patient has the same reason for participation, but trials are essential for developing new and improved treatments for the future. 

Elena:  

I also learned that patients can leave a trial at any time or stage if they wish. 

Dr. Singh: 

That’s a great point, Elena.  

Now that you understand more about trials, how can you find out more? 

  • Start by asking your doctor if there are any trials that are available to you—and, if there is a specific trial that they recommend for you. 
  • If there is a trial that your team recommends, ask to discuss: 
  • The treatment approach used in the study and the purpose of the trial. 
  • The risks and benefits of participation. 
  • The financial costs, if any, and if there are assistance programs to help if you need it. 
  • The location of the trial and whether it can be coordinated with your local institution if it isn’t conveniently located—or, if transportation is available. 
  • How often you will need to go to the trial site and how long the trial will last. 
  • Finally, continue to educate yourself, using resources like clinicaltrials.gov. 

Elena: 

And visit powerfulpatients.org/CLL to learn more about clinical trials and CLL research. 

Dr. Singh: 

Thanks for joining us! 

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How Does CLL Affect the Immune System?

How Does CLL Affect the Immune System? from Patient Empowerment Network on Vimeo.

Chronic lymphocytic leukemia (CLL) expert Dr. Seema Bhat explains how a patient’s immunity is affected by the disease and strategies for management.  

Seema Bhat, MD is a hematologist at The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Bhat.

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Transcript:

Katherine:

Finally, our last question. One audience member would like to know more about how CLL affects the immune system, including wound healing, and how does CLL impact this? 

Dr. Bhat:

So, patients with CLL usually have a weaker immune system. The lymphocyte, which is the white cell, which is affected in CLL, is an important part for an immune system, and due to the presence of disease, these lymphocytes – although there are lots of them in patients with CLL, they tend to be non-functional. 

“Functionally incompetent,” that’s what they’re called. And it leaves the patient’s immune deficient and susceptible to a variety of infections. Also, the lymphocyte is component – the B lymphocyte is one component of immune system. There are other components like T lymphocyte, antibody, NK cells. There’s cross-dock between the B cells and what we call, the “microenvironment,” which is made of the T cells. This cross-dock is deficient in patients with CLL, again making them immune-deficient and susceptible to infection. So, that’s one impact on their immune system. 

Sometimes, there’s something else happening in the immune system where the immune system can go crazy, or wacky, and start attacking the patient’s own blood cells leading to, for example, decrease of hemoglobin or platelets, because these are immune complications. And also, due to a weak immune system, patients with CLL can have delayed wound healing, which also predisposes them to infection. 

So, being aware of these complications is important and using appropriate precautions can be very helpful. Again, because they have a weakened immune system, vaccines are very important. Using all measures to avoid infection, hand washing, staying away from patients, from people who are obviously sick, is very important. Sometimes, patients where we see they’re’ getting frequent infections, we can use what’s called, “IVIG,” intravenous immunoglobulin. These are pre-farmed antibodies which are injected into or infused into the patient at regular intervals every 4 to six weeks, which reduce the chance of these infections.