Tag Archive for: imbruvica

Start Here: Bridging the CLL Expert and CLL Patient Voice

Chronic lymphocytic leukemia (CLL) can sometimes feel overwhelming and complicated, but what can patients and care partners do to help improve their care? With this question in mind, the Patient Empowerment Network initiated the START HERE CLL program, which aims to close the gap in the expert and patient voice to build empowerment. 

START HERE CLL Program Resources

 The program series includes the following resources:

Lisa Hatfield and Dr. Danielle Brander

Patient-Expert Q&A Webinar Topics and Key Takeaways

In the Patient-Expert Q&A webinars, CLL experts Dr. Ryan Jacobs from Levine Cancer Institute, and Dr. Danielle Brander from Duke Cancer Institute shared their expert knowledge to help patients and care partners fortify their knowledge and confidence. The webinars provided some in-depth discussion along with key takeaways derived from questions submitted by patients. Some of the discussion covered:

Among some key points from the webinars, Lisa and Dr. Jacobs discussed the importance of genetic markers. Dr. Jacobs recommended CLL patients ask their doctor about their prognostic markers. “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.”

The watch-and-wait phase of CLL, also called active surveillance, is a common term heard by CLL patients. However, there are actually two types of CLL. “While some CLL patients experience very gradual disease progression and are actively monitored during a watch-and-wait phase, other patients may experience a more expedited CLL progression and will need more frequent treatment.”

Treatment advancements for CLL have been moving forward over recent years. Dr. Brander shared her perspective about the advancements. “So over the last decade or even the last five years, for patients diagnosed with CLL, there’s been a very encouraging and marked change in the available treatments…not that many years ago we generally only had chemotherapy or chemotherapy combined with these antibody targeted treatments that we call immunotherapy sometimes. But in the last 5 to 10 years we’ve seen quite a remarkable change in treatments that target, meaning often they go after pathways or ways that the CLL cells have learned to grow or have learned to not die the way that normal cells should, die after certain time points.” 

Vaccines for those with CLL have gathered more visibility in recent years with COVID-19. Dr. Jacobs addressed some questions about vaccination and shared, “I in general am recommending, as does the CDC, to get boosted every six months for patients with any level of immune suppression and having CLL qualifies you as that. And then I recommend all of the general vaccines that come with age, like, for example, the Shingrix vaccine for shingles is now safe to give to CLL patients because it’s a conjugate vaccine, it’s not a live virus vaccine. So we’re lucky now with just standard vaccines in the U.S., there are no live virus vaccines that the CLL patient has to worry about anymore, so I definitely encourage shingles, pneumonia vaccines, boosting for COVID. We’ll see if we get an RSV vaccine, that sounds like it’s on the horizon. Flu, of course.”

Worries about CLL progression are felt by many patients, and there are some ways to stay alert for warning signs. Expert Dr. Jacobs explained signs of CLL progression including new or worsened drenching night sweats, significant changes in a patient’s ability to function, and major changes in lymph nodes over a short period. Dr. Jacobs also shared some research updates for treatments that have shown success against progression to Richter’s transformation. “…I’ve been having some recent success using CAR T in those patients, and also now have a, I was thankfully getting it sort of off-label approval to do that, but now I actually have a clinical trial investigating axicabtagene ciloleucel (Yescarta) in those patients.

Some CLL patients wonder about whether they can take a break from treatment. Dr. Brander addressed this question about BTK inhibitors. “…BTK inhibitors are given continuously, meaning, at least so far, the standard way we recommend of those treatments is that they’re taken every day, either once or twice a day, depending on which BTK inhibitor, and they’re taken every day. Unless patients run into progression, meaning the CLL learns to grow through its resistance or patients run into side effects that despite maybe team’s recommendation of changing the dose or holding the medications, that it’s just the medication is just not tolerate.”

Many CLL patients also wonder about the impact of exercise on their treatment response and their duration of treatment response. Dr. Brander explained about the impact of exercise. “I think certainly trials or studies really need to be continuing to look at this, because I think there likely are things that we can be more specific to patients about. There are studies looking at physical fitness and exercise regimens not necessarily specific to CLL, although there are studies being done in that space, but to other cancers showing that physical activity and exercise can help even for patients not on treatment maintain control of their cancer. So general daily activity and exercise are important in studies that look at how do you tailor that to an individual I think are important too.

Whether patient fatigue is originating from CLL or from symptoms of old age can sometimes be difficult to determine. Dr. Jacobs shared some insight about fatigue. “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.

Some program participants provided valuable testimonials and insights on what they learned from the START HERE CLL Patient-Expert Q&A webinars:

Testimonials:

  • I love PEN webinars because I feel I have a direct connection with the best experts. I have many questions for my team after this program, thank you.”
  • “This program was stellar. I learned a lot that I have to address with my doctor.”
  • “I have a greater comfort level with promising treatment options.”
  • “I was most interested in learning about treatment options for relapsed patients and Dr. Jacobs provided great information. THANK YOU!”
  • “This was very helpful as I consider how to support my sister who has been diagnosed with CLL.”

Learnings:

  • “What BTK and BCL-2 inhibitors are…How Fish looks for DNA for Leukemia cells. And how exercise can help any cancer patient. Thanks for the program!”
  • “Even though I am Watch & Wait, I appreciated the information and explanation of the latest treatments.” 
  • “Fantastic program. Learned about many reasons docs decide not to treat.”
  • “I learned about some potential treatment options should I relapse.”

Many other questions were raised during the CLL Patient-Expert Q&A webinars. We hope you can use these valuable CLL resources to build your knowledge and confidence toward becoming a more empowered patient or care partner.

Can CLL Patients Take a Break From BTK Inhibitors?

Can CLL Patients Take a Break From BTK Inhibitors? from Patient Empowerment Network on Vimeo.

Is it possible for chronic lymphocytic leukemia (CLL) patients on BTK inhibitors to take a treatment break? Expert Dr. Danielle Brander shares insight.

Dr. Danielle Brander is an Assistant Professor in the Division of Hematologic Malignancies & Cellular Therapy at Duke University Medical Center. Learn more about Dr. Danielle Brander.

Download Resource Guide   |  Descargar Guía en Español

See More from START HERE CLL

Related Programs:

BTK Inhibitor Treatment Side Effects: What CLL Patients Should Know

Can Lifestyle or Supplements Impact CLL Treatment Response?

Can Lifestyle or Supplements Impact CLL Treatment Response?

Empowering CLL Patients for Treatment and Survivorship

Empowering CLL Patients for Treatment and Survivorship


Transcript:

Lisa Hatfield:

So this patient is telling us that he’s trying to plan life while living with cancer. It’s a challenge. It’s hard to know where to start. Can some patients go off of ibrutinib (Imbruvica) after five years and enter a watch-and-wait kind of program? And will they be monitored during that time too, if they ever do go off of the medication?

Dr. Danielle Brander: 

Yeah, more excellent, excellent questions. So of those main categories of treatment, the BTK inhibitors are given continuously, meaning, at least so far, the standard way we recommend of those treatments is that they’re taken every day, either once or twice a day, depending on which BTK inhibitor, and they’re taken every day. Unless patients run into progression, meaning the CLL learns to grow through its resistance or patients run into side effects that despite maybe team’s recommendation of changing the dose or holding the medications, that it’s just the medication is just not tolerated.

In those cases, there are cases where we do recommend stopping the treatment because of side effects. And the key there is that patients if depending how long they’ve been on treatment or how their CLL is responding, might not need to go on to the next treatment right away.

So to answer this patient’s question, if they were to run into a side effect that wasn’t manageable, there are patients where we say, stop treatment and let’s just watch things, see if you need treatment, if your CLL has no other reason to jump into the next therapy. And there have been encouraging things that we’re learning and that I think are hopeful to this patient’s question, which is maybe in the future there are patients where we proactively can tell them to stop after a certain time because of what we’ve learned for patients so far.

But at the current moment in time, we don’t tell patients to stop at a certain amount of time. But there are trials that are looking at that after a certain number of years. And there are also trials that have followed patients who have stopped therapy and some of those patients, as I mentioned, who are told to stop treatment due to other side effects or other reasons, may go a long time, a couple of years before they need to start therapy.


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Chronic Lymphocytic Leukemia Research and EVOLVE Trial Updates 

Chronic Lymphocytic Leukemia Research and EVOLVE Trial Updates from Patient Empowerment Network on Vimeo.

What’s the latest in chronic lymphocytic leukemia (CLL) research? Expert Dr. Danielle Brander shares research updates and an update about the EVOLVE trial by the SWOG cooperative group.

Dr. Danielle Brander is an Assistant Professor in the Division of Hematologic Malignancies & Cellular Therapy at Duke University Medical Center. Learn more about Dr. Danielle Brander.

Download Resource Guide   |  Descargar Guía en Español

See More from START HERE CLL

Related Programs:

Chronic Lymphocytic Leukemia Prognosis and Treatment Factors

Chronic Lymphocytic Leukemia Prognosis and Treatment Factors

Common Chronic Lymphocytic Leukemia Symptoms and Follow-Up Tests

Common Chronic Lymphocytic Leukemia Symptoms and Follow-Up Tests


Transcript:

Lisa Hatfield:

Can you talk a little bit about the novel pathways and targets that are currently under investigation in CLL, and what are the most important highlights from those for patients and their families and care partners?

Dr. Danielle Brander:

Yes. So over the last decade or even the last five years, for patients diagnosed with CLL, there’s been a very encouraging and market change in the available treatments that is, you know, not that many years ago we generally only had chemotherapy or chemotherapy combined with these antibody targeted treatments that we call immunotherapy sometimes.

But in the last 5 to 10 years we’ve seen quite a remarkable change in treatments that target, meaning often they go after pathways or ways that the CLL cells have learned to grow or have learned to not die the way that normal cells should, die after certain time points. The two main categories of treatments that are approved for CLL treatment, either for patients as a first treatment or patients that have had treatment before including prior chemo or other agents are called BTK inhibitors or BCL-2 inhibitors.

BTK is something inside the leukemia cells. It’s also in some of our other cells. But in the CLL cells particularly, they’re very sensitive in needing that protein. So in targeting that BTK inhibitors keep the cells from getting the normal signals that they need to stay alive, and so the lymph nodes that are big get smaller, a spleen that might be big get smaller, white count eventually comes back down, for example.

And those BTK inhibitors have also already encouragingly changed over recent years. So there was…you’ll hear people say first generation, these were the first inhibitors that came out, that was a drug called ibrutinib (Imbruvica), which is still around. And then there are second generation that are approved that have come out as first treatment or treatment for previously patients that receive treatment.

Those second-generation BTK inhibitors are called zanubrutinib (Brukinsa) and acalabrutinib (Calquence) that are approved. The main other approved category of these targeted treatments I mentioned is venetoclax based treatment. And that targets something different, that targets a set of proteins inside the cell that tell the cell to stay alive too long. And so you have this accumulation and venetoclax targets that pathway. And the last thing I’ll mention about the BTK inhibitors that’s emerging is now there are trials of what are called non-covalent BTK inhibitors.

So they work in a different way, they go after BTK and so that they can work. The non-covalent, even for patients where the first and second-generation, traditional covalent BTK inhibitors I mentioned stop working, those are not yet approved officially for CLL, though they’re approved in mantle cell lymphoma. That’s a drug called pirtobrutinib (Jaypirca), that’s a non-covalent BTK. And the reason that emerging set of treatment, as I mentioned, is important is because it can work for patients where the first or second-generation covalent BTK inhibitors stop working. The venetoclax (Venclexta), as I mentioned, works by a different mechanism. So patients, of course, where the BTK stopped working, in many cases venetoclax can be helpful as well.

Lisa Hatfield:

So I read a little bit, I did a little research on trials that you’re involved in, and there is a trial the EVOLVE CLL trial, and I wonder if you can talk about that a little bit because I think it is exciting for patients to hear that there might be an option for earlier intervention. And I’m not sure if you’re allowed to talk about any results yet, but if you can speak to results, that would be great to hear about those results too.

Dr. Danielle Brander:

Well, yes and no, thank you for bringing this up because this is very important. As you mentioned, it’s called the EVOLVE study. It’s led by a national cooperative group called SWOG, meaning there are lots of places that it’s available, not just larger centers, but smaller oncology centers as well. And this is to look at what’s called early intervention, meaning as we spoke about before, most patients with CLL don’t need treatment at the time that they’re diagnosed.

The reasons for treatment are, we call those treatment indications are based on three main categories that I’ll just review. For some patients, it’s new or progressive symptoms like weight loss or, very symptomatic limiting life day-to-day activities like night sweats or fatigue, for example, that’s the first category of reasons some patients might need treatment is unmanageable side effects.

The second main category is if the lymph nodes get very large or impacting on organ function, or the same for the spleen, it’s getting very large to a certain size, or it’s affecting your ability to eat regular meals or losing weight. And then the last category of treatment indications that we generally wait to start treatment for are if it’s affecting the normal blood count.

So there’s not one magic white count where patients need to start treatment, but almost like weeds in a garden,  if those CLL cells are crowding out the red blood cells, so the hemoglobin’s falling or it’s crowding out the platelets, so the platelets are crowding and can’t grow and reach a certain threshold, then we recommend treatment. Of course, there are scattered other reasons, but those are the main three categories. And the reason of waiting to start until those are met is because historically trials have been done to look at waiting for those indications versus treating around the time of diagnosis.

Those trials so far have included, chemotherapy by itself or chemotherapy in combination. And most recently there was a trial looking at first-generation ibrutinib that was given continuously. And so far there’s been no survival. So no life expectancy benefit to early treatment versus waiting for those indications. And the other reason generally not treating all patients is because some patients never require treatment, about a quarter of patients.

So if we offer treatment to everybody, at the time of diagnosis, there are patients that would get treatment that would be exposed to side effects and never needed. But what the EVOLVE study is uniquely looking at is randomizing. And randomizing means some patients will get treatment and some patients will wait until those traditional reasons to need treatment. But for those randomized to receive therapy, it’s that venetoclax based treatment combined with this antibody called obinutuzumab (Gazyva).

And the way that treatment is given for patients, is the same way it’s given for patients who outside of the trial need treatment, meaning they get the antibody infusion, then they get the venetoclax pill, but it’s for a fixed duration, meaning a total of one year of treatment. The trial is also only for patients with higher-risk CLL. So as I mentioned, some patients never need treatment, some patients do, some patients need it quicker.

So rather than looking at this trial and saying all patients, including those with CLL, that’s likely to be slower-growing. The EVOLVE trial is only for patients who are more likely to need treatment in the next couple of years.  And the way that’s determined is a score called the CLL-IPI score, and CLL-IPI tries to identify patients more likely to need treatment in the next couple of years by a couple of key factors.

Stage at the time of diagnosis, it looks at age, and it looks at key factors of the leukemia itself, including something called deletion 17P or TP53, because that marker in the cells is a high risk of eventually needing treatment.  So to answer your question, what EVOLVE is looking at is taking higher-risk patients, so patients rather than all patients more likely to need treatment anyway, and around the time of diagnosis, randomizing to either be treated or to follow the traditional, sometimes called watch and wait or dynamic monitoring until they reach traditional markers. And ultimately, and it’ll likely take many years to look at, ultimately the question is looking at if that helps prolong patient survival by having higher-risk patients receive that fixed-duration treatment earlier in time. We don’t yet have any results or any results to share, because the study is still enrolling.

Dr. Danielle Brander:

But again, I think it’s something for patients to be aware of, because it does look at the higher risk patients. But around a year, it has to be within a year of diagnosis. So patients who are newly diagnosed, the question to ask your oncology team is “Do I qualify?” if it’s something you’re interested for, and they’ll help walk you through that. If you haven’t had markers checked, for example, it might be a good time to ask about that, to see if this is something would be available, even if not available though, it does create a time to talk to your team about the markers, because those can inform regardless of trial or not maybe what to expect in coming years and likelihood of treatment. 


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CLL Patient Expert Q&A: Dr. Danielle Brander

CLL Patient Expert Q&A: Dr. Danielle Brander from Patient Empowerment Network on Vimeo.

START HERE bridges the expert and patient voice, enabling chronic lymphocytic leukemia (CLL) patients to feel comfortable asking questions of their healthcare team with precision. In this program, CLL expert Dr. Danielle Brander speaks to managing CLL side effects, emerging novel CLL therapies and treatment options for CLL progression.

Dr. Danielle Brander is an Assistant Professor in the Division of Hematologic Malignancies & Cellular Therapy at Duke University Medical Center. Learn more about Dr. Danielle Brander.

Download Resource Guide   |  Descargar Guía en Español

See More from START HERE CLL

Related Programs:

Are There Signs of Chronic Lymphocytic Leukemia Progression?

Are There Signs of Chronic Lymphocytic Leukemia Progression?

CLL and BTK Inhibitor Treatment: What Are the Risk Factors?

Can CLL Treatment Cause Gastrointestinal Side Effects?

Can CLL Treatment Cause Gastrointestinal Side Effects?


Transcript:

Lisa Hatfield:

Welcome to this START HERE, Patient Empowerment Network program. This program bridges the CLL expert and patient voices, enabling patients and care partners to feel comfortable asking questions of their healthcare team. Joining me is Dr. Danielle Brander, a CLL specialist serving as assistant professor in the Division of Hematologic Malignancies and Cellular Therapy at Duke University Medical Center. Dr. Brander directs the chronic lymphocytic leukemia or CLL and lymphoma program and serves as primary investigator for CLL focus clinical trials. Thank you so much for joining us, Dr. Brander.

Dr. Danielle Brander:

Thanks for having me, Lisa.

Lisa Hatfield:

The world can be complicated, but understanding your chronic lymphocytic leukemia diagnosis and treatment options doesn’t have to be. The goal of START HERE is to create actionable pathways for getting the most out of CLL treatment and survivorship. 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. So let’s get started. Dr. Brander, I’d like to talk about what’s on the CLL treatment radar. There’s a lot going on in terms of emerging treatment options, clinical trial data, and other learnings from the CLL community. Before we jump into a detailed discussion, can you provide an explanation of what CLL is?

Dr. Danielle Brander:

Absolutely. So CLL, or chronic lymphocytic leukemia, we generally think of as blood cancer. But often as you hear the ending of that, the name leukemia, we also think of it as a lymphoma, meaning patients can have the spectrum of an elevated white count like you might think of in terms of a leukemia. They can also, like a lymphoma though, have enlarged lymph nodes or spleen. And often patients are diagnosed incidentally and that just means that they’re…in seeing their physician or their medical team for other reasons. And they might have had a blood test, and their white counts elevated.

Or they might notice they have a tiny enlarged lymph node or found on screening for other cancers, for example. And so the takeaway there is that many patients don’t necessarily have symptoms and certainly often many patients don’t have reasons to need to start treatment at the time they’re diagnosed. So in terms of what it is today, I think more and more patients are being diagnosed both because it is something that comes about as patients get older, but also because it’s found during routine other visits. And so more and more patients I think are found incidentally that way.

Lisa Hatfield:

Okay, thank you. So just a follow-up question to that, if a patient goes into their primary care provider and finds something unusual that might indicate CLL, will they be referred to a hematologist right away at that point? Usually?

Dr. Danielle Brander:

So that is a great question. Often they are, for example, if they’re noted to have a high white count or, specifically a type of white cell called lymphocytes. However, there are many things that can cause that or cause a small lymph node. And so, some primary care appropriately, if those changes are small and they could be due to other things like an infection, for example, then their primary care might want to follow up first. And if things go away, it may not be related to a cancer at all.

But if it’s something that persists or it seems very out of range, or primary care, who, you know, are specialists and seeing kind of changes all the time, and may say this seems a little bit out of range, then even before something’s diagnosed, patients might be referred to a hematologist or an oncologist to help with that workup. But often because primary care is so astute in seeing these things, they may counsel patients to say, let’s send this test or this test to get things going while we’re speaking to a hematologist or oncologist.

Lisa Hatfield:

We have CLL patients and care partners who are newly diagnosed in active treatment, watch and wait, and also living well with their disease. Joining this program no matter where you are in your CLL journey, START HERE provides easy-to-understand, reliable, and digestible information to help you make informed decisions. So, Dr. Brander, we’re going to get into a more detailed discussion now of CLL. Can you talk a little bit about the novel pathways and targets that are currently under investigation in CLL, and what are the most important highlights from those for patients and their families and care partners?

Dr. Danielle Brander:

Yes. So over the last decade or even the last five years, for patients diagnosed with CLL, there’s been a very encouraging and marked change in the available treatments that is, you know, not that many years ago we generally only had chemotherapy or chemotherapy combined with these antibody targeted treatments that we call immunotherapy sometimes.

But in the last 5 to 10 years we’ve seen quite a remarkable change in treatments that target, meaning often they go after pathways or ways that the CLL cells have learned to grow or have learned to not die the way that normal cells should, die after certain time points. The two main categories of treatments that are approved for CLL treatment, either for patients as a first treatment or patients that have had treatment before including prior chemo or other agents are called BTK inhibitors or BCL-2 inhibitors.

BTK is something inside the leukemia cells. It’s also in some of our other cells. But in the CLL cells particularly, they’re very sensitive in needing that protein. So in targeting that BTK inhibitors keep the cells from getting the normal signals that they need to stay alive, and so the lymph nodes that are big get smaller, a spleen that might be big get smaller, white count eventually comes back down, for example. And those BTK inhibitors have also already encouragingly changed over recent years.

So there was…you’ll hear people say first generation, these were the first inhibitors that came out, that was a drug called ibrutinib (Imbruvica), which is still around. And then there are second generation that are approved that have come out as first treatment or treatment for previously patients that receive treatment.

Those second-generation BTK inhibitors are called zanubrutinib (Brukinsa) and acalabrutinib (Calquence) that are approved. The main other approved category of these targeted treatments I mentioned is venetoclax based treatment. And that targets something different, that targets a set of proteins inside the cell that tell the cell to stay alive too long. And so you have this accumulation and venetoclax targets that pathway. And the last thing I’ll mention about the BTK inhibitors that’s emerging is now there are trials of what are called non-covalent BTK inhibitors.

So they work in a different way, they go after BTK and so that they can work. The non-covalent, even for patients where the first and second-generation, traditional covalent BTK inhibitors I mentioned stop working, those are not yet approved officially for CLL, though they’re approved in mantle cell lymphoma. That’s a drug called pirtobrutinib (Jaypirca), that’s a non-covalent BTK. And the reason that emerging set of treatment, as I mentioned, is important is because it can work for patients where the first or second-generation covalent BTK inhibitors stop working. The venetoclax (Venclexta), as I mentioned, works by a different mechanism. So patients, of course, where the BTK stopped working, in many cases venetoclax can be helpful as well.

Lisa Hatfield:

Great. Thank you so much. So I read a little bit, I did a little research on trials that you’re involved in, and there is a trial the EVOLVE CLL trial, and I wonder if you can talk about that a little bit because I think it is exciting for patients to hear that there might be an option for earlier intervention. And I’m not sure if you’re allowed to talk about any results yet, but if you can speak to results, that would be great to hear about those results too.

Dr. Danielle Brander:

Well, yes and no, thank you for bringing this up because this is very important. As you mentioned, it’s called the EVOLVE study. It’s led by a national cooperative group called SWOG, meaning there are lots of places that it’s available, not just larger centers, but smaller oncology centers as well. And this is to look at what’s called early intervention, meaning as we spoke about before, most patients with CLL don’t need treatment at the time that they’re diagnosed. The reasons for treatment are, we call those treatment indications are based on three main categories that I’ll just review. For some patients, it’s new or progressive symptoms like weight loss or, very symptomatic limiting life day-to-day activities like night sweats or fatigue, for example, that’s the first category of reasons some patients might need treatment is unmanageable side effects.

The second main category is if the lymph nodes get very large or impacting on organ function, or the same for the spleen, it’s getting very large to a certain size, or it’s affecting your ability to eat regular meals or losing weight. And then the last category of treatment indications that we generally wait to start treatment for are if it’s affecting the normal blood count.

So there’s not one magic white count where patients need to start treatment, but almost like weeds in a garden, if those CLL cells are crowding out the red blood cells, so the hemoglobin’s falling or it’s crowding out the platelets, so the platelets are crowding and can’t grow and reach a certain threshold, then we recommend treatment. Of course, there are scattered other reasons, but those are the main three categories. And the reason of waiting to start until those are met is because historically trials have been done to look at waiting for those indications versus treating around the time of diagnosis.

Those trials so far have included chemotherapy by itself or chemotherapy in combination. And most recently there was a trial looking at first-generation ibrutinib that was given continuously. And so far there’s been no survival. So no life expectancy benefit to early treatment versus waiting for those indications. And the other reason generally not treating all patients is because some patients never require treatment, about a quarter of patients. So if we offer treatment to everybody, at the time of diagnosis, there are patients that would get treatment that would be exposed to side effects and never needed. But what the EVOLVE study is uniquely looking at is randomizing. And randomizing means some patients will get treatment and some patients will wait until those traditional reasons to need treatment. But for those randomized to receive therapy, it’s that venetoclax based treatment combined with this antibody called obinutuzumab (Gazyva).

And the way that treatment is given for patients, is the same way it’s given for patients who outside of the trial need treatment, meaning they get the antibody infusion, then they get the venetoclax pill, but it’s for a fixed duration, meaning a total of one year of treatment. The trial is also only for patients with higher-risk CLL. So as I mentioned, some patients never need treatment, some patients do, some patients need it quicker. So rather than looking at this trial and saying all patients, including those with CLL, that’s likely to be slower-growing. The EVOLVE trial is only for patients who are more likely to need treatment in the next couple of years.  And the way that’s determined is a score called the CLL-IPI score, and CLL-IPI tries to identify patients more likely to need treatment in the next couple of years by a couple of key factors.

Stage at the time of diagnosis, it looks at age, and it looks at key factors of the leukemia itself, including something called deletion 17P or TP53, because that marker in the cells is a high risk of eventually needing treatment.  So to answer your question, what EVOLVE is looking at is taking higher-risk patients, so patients rather than all patients more likely to need treatment anyway, and around the time of diagnosis, randomizing to either be treated or to follow the traditional, sometimes called watch and wait or dynamic monitoring until they reach traditional markers. And ultimately, and it’ll likely take many years to look at, ultimately the question is looking at if that helps prolong patient survival by having higher-risk patients receive that fixed-duration treatment earlier in time. We don’t yet have any results or any results to share, because the study is still enrolling.

But again, I think it’s something for patients to be aware of, because it does look at the higher risk patients. But around a year, it has to be within a year of diagnosis. So patients who are newly diagnosed, the question to ask your oncology team is “Do I qualify?” if it’s something you’re interested for, and they’ll help walk you through that. If you haven’t had markers checked, for example, it might be a good time to ask about that, to see if this is something would be available, even if not available though, it does create a time to talk to your team about the markers, because those can inform regardless of trial or not maybe what to expect in coming years and likelihood of treatment.

Lisa Hatfield:

Great, thank you for that. So as a cancer patient, one of the biggest questions I had when I was diagnosed, you hear the word “cancer” or in this case “CLL leukemia.”Two questions. One of them, is there a cure for CLL? And if not, are any of the…are there any trials looking at a cure for CLL?

Dr. Danielle Brander:

Yes. Excellent. An understandable question. Traditionally, we say that CLL or others slower-growing, or sometimes you’ll hear the term indolent lymphomas, do tend to be slower-growing.  Some patients don’t need treatment. But the flip side of that is we generally think of them as not curable, that they’re a chronic condition and that treatment, the goal of treatment is to knock it down and relieve whatever symptoms or indications or reasons you’re starting treatment are.

But at some level, we historically think of CLL as either eventually coming back or sticking around, so to speak. However, I think most oncologists, most those in the field, feel that some of the treatments that are around or in combination, that we’re going to have some patients that have maybe what a term might be functional cure or individual, cure-like condition.

Meaning if our newer treatments for some patients can knock down the CLL so much that it either doesn’t come back or take so long to even show itself again, in a way that serves as what the purpose of cure, really is, which is to get it down to levels that it’s not causing problems or not coming back, for the lifetime of the patient. Bone marrow transplant is the only therapy historically that has been cured, has offered a cure for some patients. The downside and the reason that most patients aren’t referred to for bone marrow transplant is the risk side of it. Meaning, unfortunately, a bone marrow or stem cell transplant has such a high risk of directly causing side effects.

That could be life-limiting or chronic side effects from the transplant itself versus the agents available now that we aren’t using or referring to bone marrow transplant nearly as much, but I think it’s really encouraging what we’re seeing in responses. So we talked already about those main categories of BTK inhibitors or venetoclax, I didn’t yet talk about, but there are many trials that have looked at those in combination, or CAR T, for example, or bispecific antibodies that are knocking down the CLL to such low levels. But the hope is that serves as a way of functional cure. But it’s going to take time to see if that’s the case. But we’re all very encouraged and really believe that that’s on the horizon.

Lisa Hatfield:

Great. Thank you so much. And even a functional cure sounds really hopeful, so I’m happy to hear that term. Thank you. And I want to be cognizant of your time and the time of everybody watching. So we are going to move into some of the questions that we’ve received from you watching this, patients. Remember, as patients, we should always feel empowered to ask our healthcare providers any and all questions we might have about our treatment and prognosis. Please remember, however, this program is not a substitute for medical care and always consult with your own medical team. So, Dr. Brander, let’s start here. How do you explain, you kind of covered this a little bit, CLL treatment options and prognosis to your newly diagnosed patients? And I think that the prognosis piece is really important, especially if they do start treatment. 

Dr. Danielle Brander:

Sure, absolutely. So, what are the things we’re looking for in terms of needing treatment?  Because some of those, especially the symptoms we’re noting a lymph node or spleen, for example, or symptoms of anemia, which is low red cells or bleeding from low platelets, it’s helpful for patients to understand what we’re looking for, but, of course, in the time between visits those are the things we want to help patients with if they notice.

And so we encourage them all the time to call our triage or send us, you know, most electronic medical records now, have ways to send your team a message. And we want to know about that from patients in between visits. In terms of prognosis, as I mentioned before, there are other CLL-specific labs usually on the blood, meaning a regular blood draw.

Most patients don’t need another lymph node biopsy or a bone marrow biopsy, though that happens in some cases. And two of those or some of those key markers I mentioned before, but they test in the leukemia, there’s one test called the FISH, F-I-S-H, it’s not specific to CLL, we use it in other cancers. But it’s to look for specific changes in the leukemia genomics, meaning the DNA, the genetic material of the leukemia, not genetics you’re born with, but the cancer itself.

And there are specific patterns and that can be helpful as I sit down with patients to say this isn’t 100 percent, but this is kind of what to expect and likelihood of needing treatment over the next couple of years. There’s another test called IGHV, another mutation test TP53 kind of beyond this to go over right now, but as you mentioned, I think it’s important to meet with your medical team and say, ‘How does this pertain to me specifically?”

In terms of prognosis, I think there’s two parts to that of understanding what to expect. There’s likelihood of needing treatment, there’s likelihood of time to treatment, and those kind of markers and staging system help in a good way. Right now, our historical expectations, meaning 5 or 10 years ago, we could often also sit with patients and say, “This is the prognosis in terms of survival.” Expected life expectancy on average, but in a good way, most of our systems nowadays with the newer treatments likely vastly underestimate patient survival, meaning those systems were designed when we only had chemotherapy treatments.

Now, we know patients even with the highest risk markers, the faster progressions are living, you know, years and years beyond what was expected with chemotherapy. So I just caution especially materials around from just a couple of years ago that likely they don’t pertain, but they can be helpful in knowing what to expect.

Lisa Hatfield:

Great, thank you for that. Answering that question. We have a couple of questions about BTK inhibitors, and you already talked a little bit about the role of those and why they’re significant in treating CLL. But another patient’s asking about the, of course, a lot of patients wonder, what are the side effects? They hear chemo and like, “Oh, my gosh, the side effects are going to be off.” Can you talk about the side effects and even maybe some unusual side effects that you’ve heard of from patients when using the BTK inhibitors?

Dr. Danielle Brander:

Sure, absolutely. And so again, really important, these are things that as we maybe anticipate patients are going to start treatment, this is a long discussion of deciding between treatment, for example, as first treatment. There’s no trial saying one path is necessarily better than the other. So we try to individualize choosing between BTK inhibitors or that venetoclax-based therapy I mentioned. Some of that though comes about and what expected side effects are expected side effects for the individual. I try for patients to hear it from myself, other members of the team, the nurse, our pharmacist, for example.

And so patients shouldn’t feel overwhelmed to keep asking about what to expect or new side effects. There are some side effects we talk about regardless of the treatment. So I’ll just point out, anytime you’re starting treatment, you’ll hear the team talk about risk for infection, monitoring for fevers, reaching out to us about those kinds of side effects, lower blood counts that can happen regardless, not specific to BTK though it can happen there as well.

There’s some specifically though with BTK inhibitors, we ask patients to watch out for. Some BTK inhibitors can cause some cardiovascular side effects, meaning watching out for funny beating of the heart or what we call palpitations, skipped beats. There can be arrhythmias, some patients can have with time elevation in their blood pressure, for example. And then risk for bleeding, meaning BTK inhibitors affect how the platelets stick together similar to what aspirin does.

So the platelet levels may be normal but patients might have easier bruising, just generally manageable. But if there’s any kind of bleeding, certainly the team should be aware. It’s also the reason though, if you’re on a BTK inhibitor and you have a planned surgery or procedure, let your team know, because we may recommend or a lot of times recommend holding the medication before and after certain surgeries or procedures.

Other side effects can be muscle or joint aches. Some patients have some gastrointestinal side effects like looser stools or sensitivities to certain food causing looser stools, for example. And then there are some that are specific to the individual BTK inhibitor. This is the one point I’ll mention that first-generation BTK inhibitor ibrutinib, part of the reason for the second-generation zanubrutinib and acalabrutinib is not necessarily of them working better but to have less of these side effects that I just mentioned.

Lisa Hatfield:

Great, thank you for that. So this patient is telling us that he’s trying to plan life while living with cancer. It’s a challenge. It’s hard to know where to start. Can some patients go off of ibrutinib? I don’t say…ibrutinib after five years and enter a watch-and-wait kind of program. And will they be monitored during that time too, if they ever do go off of the medication?

Dr. Danielle Brander:

Yeah. So again, more excellent, excellent questions. So of those main categories of treatment, the BTK inhibitors are given continuously, meaning, at least so far, the standard way we recommend of those treatments is that they’re taken every day, either once or twice a day, depending on which BTK inhibitor, and they’re taken every day. Unless patients run into progression, meaning the CLL learns to grow through its resistance or patients run into side effects that despite maybe team’s recommendation of changing the dose or holding the medications, that it’s just the medication is just not tolerated.

In those cases, there are cases where we do recommend stopping the treatment because of side effects. And the key there is that patients if depending how long they’ve been on treatment or how their CLL is responding, might not need to go on to the next treatment right away.

So to answer this patient’s question, if they were to run into a side effect that wasn’t manageable, there are patients where we say, stop treatment and let’s just watch things, see if you need treatment, if your CLL has no other reason to jump into the next therapy. And there have been encouraging things that we’re learning and that I think are hopeful to this patient’s question, which is maybe in the future there are patients where we proactively can tell them to stop after a certain time because of what we’ve learned for patients so far. But at the current moment in time, we don’t tell patients to stop at a certain amount of time.

But there are trials that are looking at that after a certain number of years. And there are also trials that have followed patients who have stopped therapy and some of those patients, as I mentioned, who are told to stop treatment due to other side effects or other reasons, may go a long time, a couple of years before they need to start therapy.

Lisa Hatfield:

Okay, great. Thank you. I’m going to add one little question there too, if you don’t mind. So we’ve talked about trials a little bit, and I know that patients can go to clinicaltrials.gov, but what if a patient lives in an area that doesn’t have a major academic center or maybe trials aren’t being done very much in their area? Do you have a recommendation for patients? Should they just ask their doctor about trials if say, for example, they want to go on one of these trials? What recommendations do you have for those patients?

Dr. Danielle Brander:

Yes, absolutely. Starting with your healthcare team is very helpful to navigate to the right site. You mentioned the SWOG trial, which is online at a lot of the community and academic sites. So I would say also don’t or I encourage patients that just if they’re at a smaller site, it doesn’t mean there aren’t trials available. And then without going into all the individual, I guess societies and advocacy networks I really think that that’s been a tremendous benefit for patients is that there are societies through, you know, having leukemia or lymphoma, for example, that list or want to help patients connect them to what available trials there are.

Because while we think of trials as maybe the treatment, the reality is that a lot of trials are looking at other things too, patient’s physical function, patient’s other aspects of life besides the drug itself. So yes, I think that’s a great question for patients to be thinking about.

Lisa Hatfield:

Great, thank you. And you’re right, talking about access to trials is a whole other issue that will probably take up an entire program. But there are the advocacy networks out there, even Patient Empowerment Network. We can maybe help with that a little bit too. So we have another patient who is concerned about chances of relapse and is asking if there are any lifestyle changes through diet and supplements or anything that you can speak to that may enhance their response or their duration response to the treatment?

Dr. Danielle Brander:

Yeah. So a very very great question to bring about. And this is the one area, understandably where many of us feel frustrated because we can’t tell patients specifically that this trial has been done and says this specific diet is helpful or this specific lifestyle change is helpful to make the treatment work for longer. I think some of that is because some of the general advice we give meaning maintaining daily activity or a well-balanced diet sound non-specific or simple, but I think do help in patients staying in an overall general health wellness so that they can benefit from the treatment and potentially have less side effects from the therapy.

But getting back to the question we just talked about, I think certainly trials or studies really need to be continuing to look at this, because I think there likely are things that we can be more specific to patients about. There are studies looking at physical fitness and exercise regimens not necessarily specific to CLL, although there are studies being done in that space, but to other cancers showing that physical activity and exercise can help even for patients not on treatment maintain control of their cancer. So general daily activity and exercise are important in studies that look at how do you tailor that to an individual I think are important too?

Lisa Hatfield:

All right. So probably time for this last question from a patient. “As a CLL expert, how do you help empower your patients so they can get the most out of their CLL treatment and survivorship? How do you work with them as a team to make sure, I guess they’re having the best outcome they can?”

Dr. Danielle Brander:

Absolutely. So it starts at the start. I guess so for conversations, meaning for those that don’t need treatment right away building the relationship, understanding how I can help patients and their caregivers help, for example, they like to learn how much they want to know, what resources can I connect them with. And then I think it’s important for them to have other team members that they can go to and talk to and hear it from, because sometimes the same information we can just share in different ways or approach differently. The nurse on our team or our pharmacist or I work with a wonderful group of nurse practitioners and physician assistants as well. And so from the beginning, I want patients to feel free to ask the questions that come to mind.

It’s amazing, of course, during the course of the visit when you’re going over your labs and that, that sometimes it’s easy to forget the questions you came in with. So, of course, anytime you can write them down before coming in, write them down and then maybe prioritize because all of us…I think it’s hard to remember everything. So prioritizing the questions we want to make sure we get to and go over as well as know that these same questions are going to mean different things to you the longer you’re living with your CLL. And so it’s okay to ask the same questions. Again, there’s never a question that any of us mind going over several times. And then just know how the team can help you. You know, are you coming? How much information do you want?

How much input do you want us to put? And what is your importance and priority? At the end of the day, I want all patients to know no one knows what it is, like living with it. No one knows what’s most important as much as you and your family or your caregiver team does. And I learn just as much from patients and the way they share their experiences. There’s a lot we can look at a group of patients with CLL and say how different each patient’s experiences, who needs treatment or not, who has side effects or not. But no one’s going to know as much as as you do living with it. And it’s our hope to help you wherever you are in your journey or whatever ways that we can help you.

Lisa Hatfield:  

Well, and I appreciate your comment that we can ask the same questions over and over if we need to. I know my oncologist when I first met with him, I felt guilty taking in more than two questions, but right before he moved, I took in a long, I rolled up a piece of paper, a long scroll, and I said, I have some questions for you, but I knew they were all repeat questions. But it does give us a little bit of peace of mind just hearing it again from somebody, especially in those initial phases of treatment, just hearing it, even if you have to hear it again and again. So thank you for mentioning that. It makes us feel a little more confident in taking those concerns to our providers, even if they’re repeated concerns. 

Lisa Hatfield:

Dr. Brander, thank you so much for being part of this Patient Empowerment Network START HERE Program. It’s these conversations that help patients truly empower themselves along their treatment journey. And on behalf of patients like myself and those watching, thank you very much for joining us.

Dr. Danielle Brander:  

Thank you for having me.

Lisa Hatfield:  

I’m Lisa Hatfield, thank you for joining this Patient Empowerment Network program. 


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Why Is Early Stage Chronic Lymphocytic Leukemia Treatment Delayed?

Why Is Early Stage Chronic Lymphocytic Leukemia Treatment Delayed? from Patient Empowerment Network on Vimeo.

What’s the reasoning behind delaying chronic lymphocytic leukemia (CLL) treatment in early stages?  Expert Dr. Ryan Jacobs explains results of the CLL12 study and why active surveillance is an approved approach in early stage CLL.

Dr. Ryan Jacobs is a hematologist/oncologist specializing in chronic lymphocytic leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

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Transcript:

Lisa Hatfield:

Why are CLL patients not getting treatment in early stages of disease?

Dr. Jacobs:

So interestingly enough, in the recently reported final analysis of the CLL12 study, which was trying to look at this particular question, do we, with our newer agents, gain anything from starting treatment earlier? Because, I’ll just remind the audience that there’s never been a study that shows giving an asymptomatic patient chemotherapy, ultimately improves survival. So we don’t do it. And with the important also caveat that I…there is a percentage of CLL patients that will never progress clinically. And I have patients in my clinic that have been on active surveillance for more than two decades.

So, with all that in mind, with our newer treatments, and, of course, ibrutinib (Imbruvica) was the first newer of these targeted agents, these small molecule inhibitors, there was this question, well, now that we have these newer treatments, can we start treatment early and does it make a difference? And so they took high-risk CLL patients and randomly assigned them in a blinded way to placebo or ibrutinib and followed them for years. And they just recently shut down the study because after many years there is still no difference in survival. And, of course, there are side effects with treatment and there’s financial toxicity for treatment too.

So with no survival benefit, we are, in any study in asymptomatic patients, we are not treating asymptomatic patients. And I have patients that experience hearing that in different ways. I would say three-quarters are really happy and love the fact that they can see me in six months to check in. But then there is the percentage that are kind of angry and think that we’re missing the boat here by just watching, so to speak. But the data supports active surveillance.


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Why Does Bruising Occur in Chronic Lymphocytic Leukemia?

Why Does Bruising Occur in Chronic Lymphocytic Leukemia? from Patient Empowerment Network on Vimeo.

Bruising is a chronic lymphocytic leukemia (CLL) side effect in some patients, but why does it happen?  Expert Dr. Ryan Jacobs explains different reasons that bruising may occur more easily in CLL patients. 

Dr. Ryan Jacobs is a hematologist/oncologist specializing in chronic lymphocytic leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

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Transcript:

Lisa Hatfield:

What causes persistent bruising? Are there more side effects from vaccines that have been discovered recently that were not discovered initially?

Dr. Jacobs:

Yeah. So there are a lot of different things that can cause bruising in a CLL patient. I think one thing that’s just worth noting is that we bruise easier as we get older. Our skin tends to thin, and often older patients are on medicines that interfere with platelet aggregation, and maybe even they’re on blood thinners. So, of course, all those things can contribute to bruising. CLL is a cancer of the aging patient population, average age 70, 71.

So these are patients that are going to be noting more easy bruising in general. But what are the CLL-specific factors that can lead to increased bruising? I would highlight, if patients are having decreasing platelet counts because of bone marrow involvement. And then the…what the second part of this question addresses is the use of Bruton tyrosine kinase inhibitors, specifically and the covalent Bruton tyrosine kinase inhibitors like ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa). They all in varying ways, have been shown to lead to increased bruising and potentially bleeding. And they do tend to interact with the platelets in a way that leads to some dysregulation in platelet aggregation.


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Does Untreated Asymptomatic CLL Carry Risks?

Does Untreated Asymptomatic CLL Carry Risks? from Patient Empowerment Network on Vimeo.

Does untreated chronic lymphocytic leukemia (CLL) that’s asymptomatic carry risks? Expert Dr. Ryan Jacobs explains CLL characteristics that are checked, research results from the CLL12 trial, and trends for treating vs. not treating asymptomatic CLL.

Dr. Ryan Jacobs is a hematologist/oncologist specializing in chronic lymphocytic leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

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Transcript:

Lisa Hatfield:

So, Dr. Jacobs, if CLL is left untreated due to no symptoms, and the white blood count is up to 150-200,000. Can it transform to another type of cancer? And what are the dangers of not treating without symptoms?

Dr. Jacobs:

Yeah, so a couple points are highlighted in that question. One I would say, is that I would like to highlight, is that there is no specific white blood cell count that says you need to treat CLL. We do sometimes reference doubling time in less than six months or 50 percent or less than two months. But I would just note that actually a lot of specialists are de-emphasizing that criteria even as well. So we are really just focusing on, in terms of objective values on the complete blood count, looking at the hemoglobin and is it less than 10 platelet count? Is it less than a 100,000? And we’re using those as a guide to how healthy the bone marrow is, how much the CLL has invaded the bone marrow, but not specifically the white blood cell count.

So the answer is no, there’s no inherent danger to continuing a patient even into the 100 plus range on observation. Now, in terms of the second part of that question, are there any dangers to not treating asymptomatic patients, we actually just conclusively had the final report, the most recent report of trying to treat asymptomatic patients. And it was the CLL12 trial that was just presented at the European Hematology Association meeting that compared ibrutinib (Imbruvica) to a placebo in a blinded trial in higher risk CLL patients that didn’t meet clinical criteria to treatment. And the overall survival of the two groups after several years of following patients was, there was no difference in overall survival. So yet another study confirming that there’s no…you do not improve survival of patients when you try to treat them early.


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CLL Genetic Markers: What Should I Ask About Prognostic Factors?

CLL Genetic Markers: What Should I Ask About Prognostic Factors? from Patient Empowerment Network on Vimeo.

What’s key for chronic lymphocytic leukemia (CLL) patients to know about genetic markers? Expert Dr. Ryan Jacobs explains genetic markers checked in standard CLL testing, questions to ask your doctor, and common treatments used with specific genetic markers.

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

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Transcript:

Lisa Hatfield:

“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 can 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 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 (Venclexta). And so we tend to treat those patients with a drug like acalabrutinib (Calquence) or zanubrutinib (Brukinsa) 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 it 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 (Gazyva) 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 who are still free of progression.

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CLL & Relapse: A Look at Available Treatment Options

CLL & Relapse: A Look at Available Treatment Options from Patient Empowerment Network on Vimeo.

What chronic lymphocytic leukemia (CLL) treatment options are available for relapsed patients? Expert Dr. Ryan Jacobs explains options for patients in relapse and for those seeking additional treatments.

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

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Transcript:

Lisa Hatfield: 

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 (Venclexta). 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 (Imbruvica) or acalabrutinib (Calquence) or zanubrutinib (Brukinsa).

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 inhibitors and venetoclax and are looking for other options.


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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. 

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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.  

What Do You Need to Know About Follicular Lymphoma?

What Do You Need to Know About Follicular Lymphoma? from Patient Empowerment Network on Vimeo.

What should you and your loved ones know after a follicular lymphoma diagnosis? This animated video provides an overview of follicular lymphoma, current treatment options, and important steps for engaging in your care.

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Transcript:

What do you need to know if you or a loved one has been diagnosed with follicular lymphoma? 

Follicular lymphoma is a type of B-cell non-Hodgkin lymphoma. It is typically slow-growing and can begin in the lymph nodes, bone marrow, or other organs. The disease does not always cause symptoms. But if symptoms are present, they can include swollen lymph nodes, fever, unintentional weight loss, and night sweats.  

Follicular lymphoma is classified as “low grade” if the disease is slow-growing, or “high grade,” if the disease is more aggressive and growing more rapidly. 

Follicular lymphoma is staged to understand where the lymphoma is in the body and to help determine which treatment options are best. There are four stages – 

  • Stage I, in which the lymphoma is localized in one single lymph node area or one non-lymph node site. When there is a non-lymph node site involved, an “E” is added to the stage, meaning “extra nodal.” 
  • In stage II, the lymphoma is in two or more areas on one side of the diaphragm. Again, “E” designation means that there is a non-lymph node site involved. 
  • Stage III means the lymphoma is in two or more lymph node areas above and below the diaphragm. 
  • And finally, stage IV is when the lymphoma is widespread, with involvement above and below the diaphragm, including at least one non-lymph node site. 

Unlike in many other types of tumors, stage IV follicular lymphoma is often very treatable, because lymphomas tend to be sensitive to many different therapies. 

Treatment recommendations are based on a variety of factors, including: 

  • Disease stage 
  • Tumor size and tumor grade 
  • Disease symptoms 
  • And a patient’s age and overall health 

For some patients, treatment doesn’t begin right away, and an approach called “watchful waiting,” “observation,” or “active surveillance” is used to monitor the progression of the disease. This usually involves regular oncology clinic visits and lab checks – and sometimes repeat imaging scans. 

When it is time to treat, options may include: 

  • Radiation therapy 
  • Chemotherapy 
  • Targeted therapy 
  • Immunotherapy 
  • Or cellular therapy, such as CAR T-cell therapy or a bone marrow transplant.
  • Your physician may also recommend clinical trial options. 

Now that you understand more about follicular lymphoma, how can you take an active role in your care?  

  • First, continue to educate yourself about your condition. Ask your healthcare team to recommend credible resources of information.  
  • Next, understand the goals of treatment and speak up about your personal preferences.
  • Consider a second opinion or a consult with a specialist following a diagnosis to confirm your treatment approach.
  • And, write down your questions before and during your appointments. Visit powerfulpatients.org/FL to access office visit planners to help you organize your thoughts. Bring loved ones to your appointments to help you recall information and to keep track of important details.
  • Ask your doctor whether a clinical trial might be right for you.
  • Finally, remember that you have a voice in your care. Don’t hesitate to ask questions and to share your concerns. You are your own best advocate. 

To learn more about follicular lymphoma and to access tools for self-advocacy, visit powerfulpatients.org/Follicular. 

How Do Genetic Mutations Impact a CLL Patient’s Prognosis?

How Do Genetic Mutations Impact a CLL Patient’s Prognosis? from Patient Empowerment Network on Vimeo.

What is the best approach for chronic lymphocytic leukemia (CLL) patients with genetic mutations? CLL expert Dr. Seema Bhat shares how mutations impact prognosis and treatment.

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:

Okay, that’s great. Here’s one from Phil, “How do mutations affect longevity when surviving CLL? What new treatments help with P53 mutation?”  

Dr. Bhat:

So, there are certain prognostic markers for CLL, meaning certain tests that can tell us how a particular patient is expected to do. Some of these tests detect presence or absence of mutations in certain genes. For example, the IGHV gene can be mutated or unmutated. 

In patients with mutated IGHV, they do well, and patients with unmutated IGHV tend to have a more aggressive disease and may require treatment sooner. Similarly, TP53 mutations also tend to require treatment sooner, and more of these mutations do not respond well to conventional chemotherapy. However, targeted therapy has changed the outlook for these mutations, and it works very well for both these mutations. 

Managing CLL Symptoms and Treatment Side Effects

Managing CLL Symptoms and Treatment Side Effects from Patient Empowerment Network on Vimeo.

Chronic lymphocytic leukemia (CLL) expert Dr. Seema Bhat reviews common CLL symptoms and treatment side effects and approaches for managing them. Dr. Bhat stresses the importance of sharing any issues they may be having with their healthcare teams.

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:

Can you please talk about common side effects of CLL – which, of course, we’ve covered already, but both the ones from the disease itself and then ones related to treatment, and what can be done about these? 

Dr. Bhat:

So, disease-related side effects, or we call them disease-related symptoms, include fatigue as a common symptom. Unintentional weight loss can happen. Fevers, chills, or drenching night sweats can happen. We call them, “B symptoms.” Spleen can enlarge, and the enlargement can cause belly pain or feeling of fullness quickly after a meal since spleen is close to our stomach, and as it enlarges, it limits the space stomach can take up in the belly. Lymph nodes can enlarge and can get uncomfortable. So, if any of these symptoms happen, then we have to treat the CLL, and once we start treating the CLL these symptoms should go away. 

As far as treatment-related side effects are concerned, for example, BTK inhibitors are associated with a certain set of side effects. For example, patients can have muscle cramping, muscle pain, joint pain. Patients can have diarrhea. Some of the side effects that we worry about is change in heart rhythm, for example, atrial fibrillation. We talked about that, or increased risk of bleeding.  

Those are some of the side effects we worry about, and if those were to develop, then, of course – for example, a patient has atrial fibrillation, and if it’s symptomatic, we hold the medication. We take care of the atrial fibrillation, usually in collaboration with cardiologists, and once that’s under control, then we have to decide what to do with the treatment. If the atrial fibrillation is under control, we can re-initiate the treatment, or we can go to one of the next-generation BTK inhibitors – the acalabrutinib (Calquence), the pirtobrutinib (LOXO-305), which have less of those side effects. 

Bleeding tends to be a concern, but anything that reduces the risk of bleeding like other medications, aspirin, clopidogrel (Plavix), other blood thinners, we can avoid them, monitor these patients very closely for any of these side effects, so that’s critical. With venetoclax, it’s usually very well-controlled. It’s the initial part of treatment that tends to be a little bit intensive because of the specific side effect called, “tumor lysis syndrome,” which means that the drug works very quickly, and cells die off quickly, they can release stuff in the blood, and things can collect in the blood. 

Uric acid can go up, electrolytes can be up, any number can go up. So, we are aware of this side effect, and we actually pre-emptively have things in place that can prevent this from happening, or if it happens, we manage it right away. For example, venetoclax has a specific dose initiation. For example, it’s called, “dose ramp-up.” We start it at a lower dose, 20 milligrams, for one week. Escalate it to 50 the next week, 100 the third week, 200 fourth week, and 400 the last week, which is the standard dose. They continue on 400 from there onward. 

And even with the slow dose escalation, in the early couple of weeks, we monitor them very closely. Once we initiate a dose, we bring them back to the clinic to recheck their blood work to see if there are any changes. If any changes have happened, we hydrate them, initiate medication for their tumor lysis syndrome. 

If the risk of tumor lysis is very high, then we monitor then admit them to the hospital. Otherwise, long-term side effects of venetoclax, what we have noticed mostly is gastritis, most side effects – mostly diarrhea. But that’s usually well-controlled. We can manage it well with supportive care.