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PODCAST: CLL Patient Expert Q&A: Dr. Danielle Brander

 

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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. 

Can Bone Marrow Return to Normal After CLL Treatment?

Can Bone Marrow Return to Normal After CLL Treatment? from Patient Empowerment Network on Vimeo.

Is it possible for chronic lymphocytic leukemia (CLL) patients to achieve normal bone marrow after CLL treatment? Expert Dr. Ryan Jacobs explains MRD-undetectable status and the typical time period to deep CLL remission.

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:

This patient is asking, upon completion of venetoclax (Venclexta) and obinutuzumab (Gazyva) and achieving MRD-undetectable status, how long does it take your bone marrow to achieve improved hemoglobin, hematocrit platelets, white blood cells? And does it always return to normal? And I might add in there just any kind of treatment, does the bone marrow typically return to “normal”? And how long does that take?

Dr. Jacobs:

So the majority of patients treated in the first-line setting and actually in the relapse setting with a combination of venetoclax and obinutuzumab, will have their CLL go into such a deep remission that we cannot detect it in 1 out of 10,000 cancer cells. So that is called MRD-undetectable. Those patients are usually also in complete remission, which means if you look at the bone marrow, you’re not going to see any CLL there. So the majority of patients have their counts normalized while they’re still on the venetoclax. You take it for a year. The complete remission is usually achieved before therapy is completed. And what little, if any CLL is in the bone marrow is not causing a drop in the counts. Now, of course, patients can have the toxicity-reduced counts. And if that’s the case, if it’s a toxicity issue, then it should resolve when you stop treatment. So I would say, usually it does return to normal, if not all…when they’re on therapy, then after therapy. If it’s a relapsed patient that’s seen a lot of therapies though, the bone marrow might never return to normal. 

Lisa Hatfield:

How far out are we from curative therapies for CLL patients with the tougher prognostic indicators?

Dr. Jacobs:

So I think curative is an interesting question, and it can mean different things to different people. But we’ve already shown at the most recent American Society of Hematology meeting, when they looked at the average life expectancy of patients without CLL, since the time that ibrutinib (Imbruvica) got approved and then now CLL patients, the survival curves are overlapping. So as of now, it looks like with our newer treatments that a CLL patient should reasonably expect to live a normal life expectancy. Does that mean cure? Well, if by cure you mean, does the disease go away forever with one treatment? We still don’t think we have that therapy for most patients. But we’ll see as we get longer and longer follow-up with some of these newer agents is there are going to be a proportion of patients that never relapse, that ibrutinib is going to have the longest follow up because it was the first one. I was just looking at a poster at the European Hematology Association meeting where they’ve followed patients seven, eight years out and more than half have still not progressed that got ibrutinib as a first-line therapy. So it’s reasonable to think that maybe some will never progress.


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Should CLL Patients Worry About Enlarged Lymph Nodes?

Should CLL Patients Worry About Enlarged Lymph Nodes? from Patient Empowerment Network on Vimeo.

Should chronic lymphocytic leukemia (CLL) patients be concerned about enlarged lymph nodes? Expert Dr. Ryan Jacobs shares his perspective on when his patients start treatment due to lymph node enlargement and additional symptoms that become concerning. 

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 this patient is asking, “When you are in the watch-and-wait phase and are feeling lymph nodes getting bigger, when is it appropriate to contact your oncologist?”

Dr. Jacobs:

This is a question that comes out a lot with my CLL patients. It’s a very subjective thing. Lymph node pain, that’s what’s supposed to trigger needing treatment for CLL from a lymph node standpoint. Technically speaking, if there’s a lymph node bigger than 10 centimeters, we’re supposed to start treatment. That’s one of the criteria too. That’s one that I almost never see, because usually patients get uncomfortable with their lymph nodes or their disease progresses elsewhere significantly before a lymph node gets that big.

So discomfort or pain, and that’s up to the patient, and I tell them like, “You have to tell me if this is bad enough that you want to start treatment.” And I have patients that are very different in how they interpret that. And I’ve got some patients that have visibly enlarged neck nodes and have had it for a while, and they don’t feel like they’re bothered by them, even though they’re quite chunky.

And then I have patients that have had lymph nodes that aren’t that big that really bother them. And so we start treatments. It’s just a very subjective thing. The only part I would identify is, you don’t need to just call your oncologist if you’re just noticing a little bit of growth or a node here and there, that’s expected. If you’re on active surveillance, it is expected that over time most patients’ white count will go up. Not all, most patients’ lymph nodes will grow. Not all.

The reason I would call an oncologist to maybe schedule earlier follow-up is if there’s accelerated growth that’s persistent and maybe if it’s associated with new symptoms like feeling really badly, fevers, waking up drenched in sweat. These are all signs that maybe the lymphoma has transformed to a more aggressive type of lymphoma that’s called Richter’s transformation. So that’s when I would be concerned. But low level chronic growth that’s relatively asymptomatic, is not overly concerning. 

Lisa Hatfield:

Hey, as a blood cancer patient, the limited duration treatment sounds like a dream. So this patient is asking, is there a time-limited pill-only treatment regimen yet, or is one in the pipeline?

Dr. Jacobs:

If you live in Europe, ibrutinib (Imbruvica) and venetoclax (Venclexta) got approved. I did a lot of research on that study. The FDA didn’t look as favorably on the comparison arms of the trials that led to the approval in the EU. So we do not have FDA approval. It is on the NCCN guidelines, as an option in…or as another option, that you can consider. The research is ongoing into getting the venetoclax combination approved with the newer BTK inhibitors. I currently am putting a lot of patients on a trial that’s looking at acalabrutinib and venetoclax. So I do think we will have, for some patients, the option, that for some patients that want it, and that seem to fit the, what we ultimately decide is the best patient population for this combination, the option to give a combination of pills for a time-defined period.


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Reasons to Get Chronic Lymphocytic Leukemia Second Opinions

Reasons to Get Chronic Lymphocytic Leukemia Second Opinions from Patient Empowerment Network on Vimeo.

Why are chronic lymphocytic leukemia (CLL) second opinions a  good idea? Expert Dr. Ryan Jacobs shares his perspective on CLL second opinions and how they can help in patient care.

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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Should CLL Patients Worry About Enlarged Lymph Nodes?


Transcript:

Lisa Hatfield:

So say one of your patients, seeing you or seeing a hematologist, maybe a local hematologist who doesn’t see a high volume of CLL, and they ask if…what would, what do you think…or they ask of their doctor, what do you think of me getting a second opinion on my diagnosis? Because patients are scared for one thing and they want to make sure that they’re making the right decisions for themselves. How do you feel about patients seeking a second opinion?

Dr. Jacobs:

I always support it. Of course, with me, I am often the second or even higher number of opinions that has received. But I certainly, I’m not there at the biggest cancer center in the world. I trained there, but that’s not where I’m at now. So I’ve had patients that have gotten even a second or third opinion from me and then go off and get a fourth opinion at MD Anderson. So, in terms of what I want patients to understand with opinions is, one, if you get a lot of opinions, that can just make it kind of difficult. And, so I don’t know if I would really support a large number of different opinions.

I think certainly getting a second opinion is reasonable. But whenever you’re seeking another opinion, I think it really only makes sense if you’re going to a higher level of specification. So certainly it makes sense to go from a general oncologist, getting a second opinion from somebody like myself that sees a lymphoma as a specialty and does research in CLL. But if you’re already seeing a CLL specialist to then seek another one, I think it, yeah, maybe if you want to go to even a bigger cancer center or someone that has maybe published over more years, that’s fine.

But it certainly doesn’t make sense to go from one CLL specialist to somebody that is maybe even less focused in CLL. And sometimes you’d have to kind of be aware of just where you’re at. In general, the specialists are going to be at the larger cancer centers. You might find the name of a larger cancer center in a small cancer clinic. And it’s unlikely that just because the name of that well-known cancer center is on a small clinic site that you’re going to have access to a lot of specialists at that site, usually to support specialists. You’re having to be at a large, usually urban-located cancer center.


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Which Oncologists Are Chronic Lymphocytic Leukemia Experts?

Which Oncologists Are Chronic Lymphocytic Leukemia Experts? from Patient Empowerment Network on Vimeo.

How are oncologists designated as chronic lymphocytic leukemia (CLL) experts? Expert Dr. Ryan Jacobs explains the benefits of seeing a CLL specialist and questions to ask about their experience for your optimal care.

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 I really appreciate this question from a patient because I’m a big advocate for patients seeking out a specialist for whatever type of cancer they have, at least for the initial consult. So this patient is asking, what are the criteria used to designate certain oncologists or hematologists as CLL experts, and how much weight is given to the number of published research papers that are co-authored?

Dr. Jacobs:

So I think this question is stemming from the acknowledgment that if you can see an expert and you have that resource, it makes sense. And I always bring up to patients, if you’re going to get a hernia repair, there’s plenty of data that shows if you go to a doctor that just does hernia…go to a surgeon that just does hernia repairs versus a general surgeon that only a proportion of his practice is hernia repairs, that the negative outcomes and failures of the surgery are lower with a specialized surgeon, which makes sense. I think it’s an easy way to connect that. And there’s actually data that shows the same in CLL if you go to a doctor that focuses in CLL. And then there are, of course, different levels. But they’re going to be more likely more up to date with the recommendations, have used more of the drugs, know how to navigate the toxicities with more experience.

So it’s all about truly what labels an expert is experience. And there’s not an official club, or a test or a, you know, a voting in. It’s just essentially oncologists that are able to, with the volume of their practice, focus in CLL or hematologic or lymphoid malignancies. So it’s quite rare to be able to find somebody that only sees CLL. I don’t even only see CLL. I do see other lymphomas. And I have five other lymphoma doctors in my practice here, but even with that many lymphoma patients, I still can’t completely fill up my clinic with just CLL.

So it’s really about how focused the practice is. Patients should feel empowered to ask oncologists what kind of cancers they treat. And, of course, there are many oncologists that have to treat everything and we need those oncologists. But it should just be understood that that oncologist couldn’t justifiably call himself a CLL expert by their practice. I think, and it’s reasonable, if you ask your oncologist what they treat and they only treat blood cancers, I think it’s safer to believe them if they identify as…I don’t think anybody’s going to try to misrepresent themselves.

But if somebody tells you that they focus in lymphoid or hematologic malignancies, and focus and are an expert in CLL, I think it’s okay to trust that. But if they’re seeing…by and large, if these doctors are having to see a wide breadth of solid tumor cancers as well, I think it’s kind of difficult to say you’re an expert in one small malignancy out of all those. But, of course, there can always be exceptions.

The question on publications, you know, that’s a different…you could go to a doctor that all they do is publish and don’t see patients very much, and you may not get the best care for your CLL. So yes, I think publications can show that they’re involved in research. But at the end of the day, in terms of treating the patient, you want an oncologist that treats a lot of CLL.


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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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Can CLL Remission Occur With Rheumatoid Arthritis Drug Treatments?

Can CLL Remission Occur With Rheumatoid Arthritis Drug Treatments? from Patient Empowerment Network on Vimeo.

Is it possible for chronic lymphocytic leukemia (CLL) remission to occur from rheumatoid arthritis treatments? Expert Dr. Ryan Jacobs explains what he’s observed in his CLL patients who also have RA and take RA 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:

Do any rheumatoid arthritis medications help prevent CLL from returning after treatment with FCR?

Dr. Jacobs:  

I do have a fair number of patients that have rheumatologic conditions and some with rheumatoid arthritis. There are some approvals there, and I in no way pretend to be an expert in rheumatoid conditions. But I do know that there happens to be some agents that are monoclonal antibodies directed against CD20 used to treat some rheumatoid conditions. So I do have some patients that are on drugs like rituximab (Rituxan) to suppress their rheumatoid condition and help prevent recurrences.

And then kind of two birds, one stone also are keeping their CLL in a clinically asymptomatic remission, I’m sure I would say, or stable disease. And it comes with the known risk for long-term antibodies, that there are some increased infections there that was particularly concerned during COVID, the worst parts of COVID. But yeah, so there are some potential treatments like that.


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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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Should CLL Patients Worry About Enlarged Lymph Nodes?


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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Addressing Racial Disparities in CLL Care

Addressing Racial Disparities in CLL Care from Patient Empowerment Network on Vimeo.

How are CLL racial disparities being addressed? Dr. Adam Kittai explains abstracts presented at the American Society of Clinical Oncology (ASCO) 2022 conference that examined CLL disparities and shares resources for patients who feel they’re struggling to receive equitable care. 

Dr. Adam Kittai is a hematologist and an assistant professor at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Kittai, here.

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Transcript:

Katherine:

We touched on research at the top of the program, but are there other areas of research that you’re excited about and that patients should know about? 

Dr. Kittai:

Yeah, so one of the things that I think is being really talked about in cancer care – and medical care in general – is if disparities exist between minority patients and white patients. And I think this is a really, really important topic.   

So, the American Society of Clinical Oncology, which had the conference recently, really made this a mainstay point of the conference this year and there were a lot of abstracts that were defining whether disparities exist and hopefully, by defining whether disparities exist, we’re able to target those disparities in order to make outcomes equal for all of our patients.  

So, in the CLL world, one of the things that I alluded to is a lot of our therapies can be really expensive. So, these new therapies are really expensive, they really widen the disparity gap for patients who are minorities, as well as patients who come from socioeconomic status.  

Katherine:

Absolutely. 

Dr. Kittai:

And so, there were two abstracts. One was an oral presentation that looked at the National Cancer Database in ASCO that showed that Black patients do have worse overall survival than white patients. And then, I actually did my own study looking at the SEER database, which also showed the same exact thing. Even when controlling for socioeconomic status.  

So, I think addressing these disparities, making sure that there’s equity amongst our patients, that everyone has access to these drugs and can afford them, especially when they make our patients live longer and are safer than chemoimmunotherapy in CLL is very, very important.  

Katherine:

Dr. Kittai, if a patient feels like they’re not getting equitable care, are there resources available for them?  

Dr. Kittai:

Yeah, so one of the things that I love about the CLL society, is that they have a section called Access an Expert, I believe. So, look on the website, I’m not sure it’s actually called Access an Expert, but it’s a way for all patients to get a second opinion from one of the CLL experts listed on the website. And so, if somebody is feeling like they’re not getting access to the most beneficial treatment, for whatever reason, seeking a second opinion and using the CLL Society’s website to find that second opinion, I think would be a great way for someone who feels that way to get access to the care that they deserve.  

I believe there are other ways to do this through the Lymphoma Research Foundation, as well as LLS. But I know for sure on the CLL Society, there is a link that you can click that you can get access to a second opinion.  

What Barriers Do CLL Patients Face in Accessing Clinical Trials?

What Barriers Do CLL Patients Face in Accessing Clinical Trials? from Patient Empowerment Network on Vimeo.

When could CLL patients run into barriers to clinical trial access? CLL expert Dr. Adam Kittai explains how access can vary, explains cooperative groups, and discusses the financial benefits of some clinical trials.

Dr. Adam Kittai is a hematologist and an assistant professor at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Kittai, here.

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Transcript:

Katherine:

What do you feel are the barriers to accessing clinical trials for patients?  

Dr. Kittai:

So, unfortunately, a lot of clinical trials are at academic centers, and so there are – and the reason that is, is that the academic centers have the infrastructure to run the clinical trial. So, as we have mentioned before, there’s a lot of visits with a lot of extra science and labs that are done associated with the clinical trial. And a lot of those things and the coordination can only be done at large centers that can open clinical trials and know how to run them.  

Similar explanation could be that that safety monitoring committee that I’d mentioned before, where the academic centers have the infrastructure to ensure safety for the patients. So, access to academic centers is a limitation to enrolling in clinical trials. That being said, there are a lot of centers that are associated with an academic center and do have a lot of the clinical trials that are available at the academic center.  

And there are also cooperative groups. These cooperative groups are called Alliance and ECOG and SWOG. And these cooperative groups are national groups that are headed by multiple academic centers in partnership with pharmaceutical companies and they typically run large Phase III medical trials that help redefine standard of care. And those particular clinical trials are often available at private practices as well.  

Katherine:

Oh, that’s great. So, patients don’t necessarily have to think about traveling to a large educational institution then to become part of the clinical trial?  

Dr. Kittai:

Not always. Not always. Typically for the Phase I, the answer is yes. But for Phase III trials, usually there’s a lot of access available for Phase III trials.  

Katherine:

What would you say to patients who may be hesitant about participating in a trial?  

Dr. Kittai:

I would say that it’s important to at least ask about what’s available. And knowing what’s available and the risks and benefits of going on a clinical trial is how you should make the determination if you should go on a clinical trial.  

Remember what I said earlier that the clinical trial is really meant to help improve safety or efficacy. So, we don’t open clinical trials that we are not hoping to improve one of those two things. And so, that is something that we should be able to put in words to you when inquiring about the clinical trial. What is the goal of this trial, and why do you think it’s going to improve safety or efficacy? And the physician who’s talking the trial with you about it should be able to answer those questions for you. So, if you have some hesitance about going in clinical trials, I would say gather your information first before making a final decision.  

Katherine:

Some patients worry about the financial aspect or impact of a clinical trial. Aren’t trials expensive?  

Dr. Kittai:

So, actually, most clinical trials are less expensive than enrolling a standard of care. So, this is actually a benefit of going on a clinical trial. Often times, the drugs in the clinical trial are a cover. So, that’s something to ask too. And so, if somebody’s having trouble getting access to novel therapy that is looking good in a specific cancer, a clinical trial is actually a way to get access to that drug without paying for it.  

Also, all clinical trials when they’re being developed are looked at by the finance committees of the hospital or wherever it’s being developed. All standard of care options are billed through the patient insurance, but all the extra stuff is usually covered by the pharmaceutical company that’s enrolling those patients onto the trial. Or I should say the supporting the clinical trial.

How Can CLL Patients Find Clinical Trials?

How Can CLL Patients Find Clinical Trials? from Patient Empowerment Network on Vimeo.

Finding a CLL clinical trial can feel overwhelming for some patients, so where can they start? CLL expert Dr. Adam Kittai shares advice, credible resources, and provides key questions to ask about trial participation.

Dr. Adam Kittai is a hematologist and an assistant professor at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Kittai, here.

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Transcript:

Katherine:

Now that we know what trials are and how they work, how can people find out what trials are available to them? 

Dr. Kittai:

Yeah. So, I’ll come back to this, but once again, talk to your physician. They’ll know what clinical trials are available at whatever site you are seeing them in. If there’s a local academic sector, the academic sector typically has clinical trials available there as well. So, it’s always good to get a second opinion in that regard.  

But one of the open access places that you can find all clinical trials is clinicaltrials.gov. This has all active running clinical trials listed out and anyone can access it. There are other societies out there that often post about clinical trials. So, there’s the CLL Society. It’s a website that you can check out that has a lot of information on there about active clinical trials in CLL. There’s also The Leukemia & Lymphoma Society, the Lymphoma Research Foundation, they all have websites available that have a lot of clinical trials listed and how to access them.  

Katherine:

Are there key questions that you think patients should ask their health care team about participating in a trial?  

Dr. Kittai:

Yeah, for sure. I think one of the key questions to ask is, is the control arm appropriate. So, what do I mean by that? Sometimes people who design a clinical trial will design a trial where the control arm is an easy control arm to beat, meaning that it’s a treatment that we wouldn’t necessarily put you on as standard of care.  

And so, I think this is a real question and an honest question that you should ask your physician prior to enrolling on a trial is, is the control arm something you would give me as standard of care. And if the answer is no, you should really consider not going on that trial or talking about why you would want to go on that trial if the control arm is not something they would put you put you on as standard of care.  

Katherine:

Right. 

Dr. Kittai:

That’s, I think, a key question to ask. And again, asking what phase it is and understanding where we are in the development.  

Are CLL Clinical Trials Safe?

Are CLL Clinical Trials Safe? from Patient Empowerment Network on Vimeo.

What should CLL patients know about clinical trial safety? CLL expert Dr. Adam Kittai explains concerns that patients should discuss with their doctor, the level of research before Phase I studies, and drug safety monitoring.

Dr. Adam Kittai is a hematologist and an assistant professor at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Kittai, here.

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Transcript:

Katherine:

Patients often have questions about safety. What are the risks of clinical trial participation?  

Dr. Kittai:

Yeah, so before anybody enrolls onto a clinical trial, you should sit with your doctor to talk about the pros and cons of entering this clinical trial. One of the things that they will talk to you about is what the expected safety of this drug is. So, you might ask yourself, well, if it’s a phase one study, first in human study, how do they know what toxicity to expect? 

Katherine:

Right. 

Dr. Kittai:

The answer is that there’s a lot of pre-human studies that occur, both in mice and monkeys and other animals, and researchers often have a good idea of what to expect in human. But there is a lot of unknowns in a phase one clinical trial. And after discussing with your doctor the pros and cons of going on a clinical trial and what side effect profile to expect from whatever drug or combination that you are about to be using, usually you go through a consent.  

Usually, you’ll get a packet, it’s about 10 to 20 pages long, written in a way that patients can understand. And it’ll have a list of toxicities that are associated with the research that is occurring. In terms of knowing what adverse events might happen, the consent is key, because it’ll have those all listed out.  

And also having the conversation with your physician about either what they’ve experienced giving this clinical trial, or what is to be expected after this drug had been introduced pre-humans.  

Katherine:

Mm-hmm. Are there protocols in place to protect patients? 

Dr. Kittai:

Yes. So, remember how we talked about in the phase one trials, we dose escalate the drug until we’ve reached some toxicity limit? There are specifically rules written out in a protocol that the doctor must follow that ensures safety for the patients that enroll in clinical trials. And that dose escalation part where we reach a toxic limit is a key part of those phase one trials that is spelled out before you even enroll.  

Usually, there’s also something called a Data Safety Monitoring Committee, as well as other committees that are looking at patients as they are receiving these drugs and move forward on clinical trials to make sure that the investigators are following the protocol as printed. That if anything happens, they document why it happened and fix the problem before it becomes another problem for a patient. So, there are very specific safety rules and a lot of redundancy to protect our patients, because the number one priority is to protect the patient. 

Katherine:

Yeah. I think you’ve already answered this, Dr. Kittai, but how do you know the medicine is safe before a human trial even begins? 

Dr. Kittai:

The answer is you don’t. There is some risk. As I said, they do test it in animals before they give the drug to humans, and they usually start at the lowest dose possible. But there are certain circumstances where there are surprising side effects that are not expected. And so, when you’re entering a first in human, Phase I trial, that is a specific risk that you do need discussed with your physician about before you enroll. 

Katherine:

Can a patient change their mind once they’ve enrolled in a clinical trial? 

Dr. Kittai:

Always. Always.  

Katherine:

Okay. 

Dr. Kittai:

They can come off the clinical trial at any point if they choose to. 

What Are the Types of CLL Clinical Trials?

What Are the Types of CLL Clinical Trials? from Patient Empowerment Network on Vimeo.

There is not just one type of clinical trial. Expert Dr. Adam Kittai explains the types and how the trials are conducted, including randomized and double-blind studies.

Dr. Adam Kittai is a hematologist and an assistant professor at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Kittai, here.

See More from CLL Clinical Trials 201

Related Resources:

CLL Clinical Trials: What Are the Phases?

 
Why Should CLL Patients Consider Participating in a Clinical Trial?

A CLL Expert Addresses Common Clinical Trial Misconceptions

Transcript:

Katherine:

Okay. You mentioned randomized clinical trials. There are a couple of other clinical trials as well. Would you define them and tell us how they’re different from one another?  

Dr. Kittai:

Yeah. So, a randomized trial is when you enroll onto a study, and you get randomly assigned to either the experimental arm or the control arm. The experimental arm is that new drug that we talked about. And the control arm is usually the standard of care. So, that’s a randomized study. 

And randomized studies are usually Phase III trials, but they can be phase two in some scenarios as well. You have – usually that’s paired with a randomized control study. So, a control study is just there’s a control arm, that’s what that means. But those usually go hand in hand. Those are usually together.  

And then another trial is the double-blind clinical trial. So, a double-blind clinical trial means that once you’re randomized to either the experimental or the control, neither you nor the physician know what drug you’re taking. And that usually is not used in CLL trials. Usually, we know what drug the patient is assigned to. And the reason why that is, is because oftentimes we’re looking out for specific adverse events or toxicities of the drugs we’re implementing at Phase III.  

And then, also, if you’re getting a triplet versus a doublet, meaning three drugs versus two drugs, it’s very hard to blind somebody to know which drug they’re on because obviously you’re getting three drugs versus two drugs. Or if an infusion is involved in one arm but not in the other arm, you obviously know that you’re getting an infusion versus an oral drug. 

Katherine:

Ah, okay. Are there common clinical trial terms that you think patients should know about? 

Dr. Kittai:

I think we covered most of them. So, knowing that phase one is typically the first in the sequence of events that I would ask your physician if this was a first in human study, right, because that comes with some special considerations knowing that you are the first human to receive a new drug is very important. Versus a phase three study where, you know, you know this drug has already gone through phase one and two in development, meaning it’s been given to a lot of patients, and they’re just looking to see if it’s better than standard of care. So, I think knowing those general concepts about what’s the difference between a phase one and a Phase III study, it’s very different. I think it’s important to keep those in mind when talking about clinical trials and discussing with your doctor.  

CLL Clinical Trials: What Are the Phases?

CLL Clinical Trials: What Are the Phases? from Patient Empowerment Network on Vimeo.

CLL clinical trials have different phases, but what happens in each phase? CLL expert Dr. Adam Kittai explains the goal of each phase in relation to research and patient care.

Dr. Adam Kittai is a hematologist and an assistant professor at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Kittai, here.

See More from CLL Clinical Trials 201

Related Resources:

What Is a Clinical Trial and What Are the Phases? 

Why Should CLL Patients Consider Participating in a Clinical Trial?

A CLL Expert Addresses Common Clinical Trial Misconceptions

Transcript:

Katherine:

Let’s talk a bit about how trials work, starting with the phases. What happens at each phase?  

Dr. Kittai:

There are actually four phases of clinical trials, although three phases are typically what’s talked about. So, Phase I is when we are first introducing the new medication, the combination, or the old medication in a new scenario for the first time in a human being.  

Phase one encompasses a lot of different things. It could be a first in-human phase one, where we’re giving the drug for the first time in a human being. It could be, as I said, the combination of drugs being used for the first time in a human being. Or it could be that we have this drug that works for this other cancer and we’re trying it out on this new cancer. So, we might have experience with this drug in another scenario, but not in the scenario we’re trying to do.  

And the primary purpose of the phase one clinical trial is to see if it’s safe. So, that’s the primary purpose of a phase one clinical trial – see if this new medication, this old medication in this new scenario, or this new combination is safe to use going forward.  

Katherine:

Right. 

Dr. Kittai:

We are able to see if it works to a small degree in the phase one trial, but typically these trials are very small with somewhere between 10 to 50 patients. And so, it’s hard to know how well this works by looking at such a small amount of patients.  

Once the Phase I trial goes forward, we usually go onto Phase II. So, one of the other points about Phase I is to determine the correct dose. Usually in phase ones, we increase the dose of the drug slowly until it meets some sort of toxicity cut-off for our patients. So, once that dose is discovered, then we move onto Phase II, and Phase II is usually a small study, usually about 50-100 patients where we’re looking at preliminary efficacy, to see if this drug, this new combination, or the drug in a new scenario, is actually working.   

And so, Phase II will tell us we think it’s working and if it looks good in phase two, it gets moved onto Phase III. Phase III is the final part of the drug development, where if it passes Phase III, it usually gets approved by the Federal Drug Administration. And Phase III is usually a randomized trial where you’re giving the new drug, the combo, or the old drug in a new situation, and you’re comparing it to whatever’s used as standard of care in that particular scenario.  

Katherine:

Right. 

Dr. Kittai:

And that’s usually a randomized study where patients are either getting the new thing or the old thing. And then, we’re determining which one works better. Lastly is Phase IV, and this is post marketing. So, after a drug gets approved, the drug company and the FDA requires just a wide scope of just data that’s collected to see how well the drug is working and if it’s safe once it’s brought out to the wider community.