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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.

See More from Thrive CLL

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Understanding CLL Treatment Classes

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Educational Resources for CLL Patients

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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. 

An Expert’s Perspective on Emerging Prostate Cancer Research

An Expert’s Perspective on Emerging Prostate Cancer Research from Patient Empowerment Network on Vimeo.

What do prostate cancer patients need to know about emerging research? Dr. Andrew Armstrong discusses developing treatments and their potential impact on prostate cancer care.

Dr. Andrew J. Armstrong is a medical oncologist and director of clinical research at the Duke Cancer Institute’s Center for Prostate and Urologic Cancers. For more information on Dr. Armstrong here.

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Transcript:

Katherine:

Are there any recent developments in treatment and research that patients should know about? 

Dr. Armstrong:

Absolutely. I would say the number one research advance has been the use of these really strong hormonal therapies in earlier and earlier disease setting. So, you may have heard of drugs like Zytiga or abiraterone, or Xtandi or enzalutamide, apalutamide or Errleada, or derolutamide or Nubeqa. Those are mouthfuls. Those are very potent hormonal pills that when used in men with advanced disease improves survival. 

And the data has supported the fact that the early use of those agents extends life even more than waiting until hormone resistance develops.  

So, if you are unlucky enough to have metastatic disease and you’re in need of hormonal therapy, giving injections that lower testosterone, which is the fuel for most prostate cancers, and then blocking testosterone with some of these newer pills extends life by years, not months. And it does so with pretty good quality of life over time.  

Of course, there are negative consequences of having no testosterone, and it’s important as part of shared decision-making to review those side effects and how that can impact quality of life negatively while extending survival.  

So, that’s a major advance. Another major advance is genetic testing and personalized medicine. In men with advanced prostate cancer, it’s now uniformly recommended that all men get hereditary testing to figure out if they inherited prostate cancer risk genes.  

These are genes such as the BRCA I and II genes, BRCA II being the most common. And these are not just breast or ovarian cancer genes. It’s important for men to realize that you can inherit these from a mother or a father, that they can create risks for multiple cancers, not just female cancers, but prostate cancer in particular. 

And now we have guided therapies, targeted therapies that can improve survival in men with these certain mutations, and if you are found to have those mutations, your family members could be tested so that they could be screened, and cancer can be picked up earlier, and perhaps they could be cured rather than suffering the fate of a more advanced diagnosis. So, really important both for yourself and for family members. 

So, those are two major advances. A third one is imaging.  

Imaging keeps getting better and better. We used to just do CAT scans, bone scans, very insensitive tests that in men with advanced disease have a hard time seeing prostate cancer, even when it’s spread. But with the advent of new technologies, like PSMA PET scan, that got approved last year. So, very new technologies. That’s transforming the way we visualize where cancer may be hiding, and for men particularly that have high-risk disease or recurrent disease or even resistant disease, we’re using those scans to guide therapy. 

Prostate Cancer Shared Decision-Making: How Does It Work?

Prostate Cancer Shared Decision-Making: How Does It Work? from Patient Empowerment Network on Vimeo.

Prostate cancer researcher Dr. Andrew Armstrong describes the benefits of the shared decision-making process and encourages patients to take an active role in their care.

Dr. Andrew J. Armstrong is a medical oncologist and director of clinical research at the Duke Cancer Institute’s Center for Prostate and Urologic Cancers. For more information on Dr. Armstrong here.

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Transcript:

Katherine:

Patients may have heard the term “shared decision-making” Let’s go into – let’s define it, though. What is it, and how does it work? 

Dr. Armstrong:

Sure. So, if you imagine you’re a patient faced with the daunting task of a new cancer diagnosis and trying to navigate decision-making around treatment, or whether you need a certain test, and those tests or treatments have harms and they have benefits, shared decision-making is really the process of communication. You know, open, transparent communication between the doctor or provider and that patient and their family and supportive spouse and others, significant others, so that everybody has complete information around the risks and benefits of a certain treatment course or management course.  

In prostate cancer, this would mean for a newly diagnosed patient, commonly first giving information about what the risks of their cancer might be, but then what the risks and benefits of various treatment algorithms might be, and explaining in ways that a patient can understand those different journeys.  

Dr. Armstrong:

And ultimately the patient makes a shared decision-making with the doctor that’s in their best interest. 

Katherine Banwell:

In your view, what role do patients have in care decisions and why should they feel empowered to speak up and be a partner in their care? 

Dr. Armstrong:

Sure. Just like there’s many different types of doctors, there’s many different types of patients, and you have some patients that have PhDs, you have some patients that are not even sure what cancer is, and it’s really important to empower every patient to understand at a level that will help them make a decision. And some patients wish to have those decisions made for them. I hear that a lot. Some patients really just want to ingest the information, not make a rash decision 

Maybe get three or four second opinions, travel around to really get the right decision. And sometimes it can take a very long time. But every patient has a different journey, and it’s important for the provider, the doctor or the nurse practitioner or the surgeon, to really understand that patient and their values to help them arrive at the decision for themselves. Because sometimes treatment decisions may have equal efficacy but different side effects.  

For example, in prostate cancer, the most common decision is between active surveillance or a radical prostatectomy or radiation of different forms, or the robot versus the open procedure, or intensity modulated radiation or brachytherapy. And these are complex decisions, and I’ve had patients go for months without making decisions. And the shared decision-making approach really can help patients make a decision as quickly as possible. 

So that they can move on and either be cured from their cancer or make the best treatment decision. 

Katherine Banwell:

Dr. Armstrong, why is it so important that patients tell their doctor about any symptoms they’re experiencing? 

Dr. Armstrong:

Certainly symptoms may or may not be related to the prostate cancer, and doctors are well-trained to sift through all of that. You know, back pain could be from a herniated disc or arthritis, but it could be a sign of metastatic disease. Weight loss could be a sign of other metabolic problems, but it can also be a sign of really advanced prostate cancer. Urinary symptoms could just be a sign of a big prostate, may have nothing to do with the cancer, or it could be a big tumor that’s blocking off your bladder.  

So, being transparent and open and just describing what symptoms and letting that physician sort through that with you to help understand what symptoms may or may not be related to the cancer, that’s really important.  

Thriving With CLL | Tips and Support for Navigating Care

Thriving With CLL | Tips and Support for Navigating Care from Patient Empowerment Network on Vimeo.

What are the key elements that help patients thrive with chronic lymphocytic leukemia (CLL)? In this webinar, Dr. Seema Bhat discusses CLL treatment and research, explains how the side effects and symptoms of CLL are managed, and shares tools for managing daily life with CLL.

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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Expert Advice for CLL Self-Advocacy

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Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today’s webinar is part of our Thrive series, and we’re going to discuss tools for navigating life with CLL. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.  

Let’s meet our guest today. Joining us is Dr. Seema Bhat. Dr. Bhat, welcome. Would you please introduce yourself? 

Dr. Bhat:

Hi, Katherine. Thank you for having me here on the program. My name is Seema Bhat, and I am an associate professor at Ohio State University with expertise in treating CLL.  

Katherine:

Excellent, thank you so much for taking time out of your schedule to join us. 

Dr. Bhat:

You’re welcome. 

Katherine:

Like all of the webinars in our Thrive series, we start with this question. In your experience, what does it mean to thrive with CLL? 

Dr. Bhat:

So, thriving with CLL to me means that we envision our patients with CLL leading normal, functional, and productive lives. You know, when patients hear the word “cancer,” or “leukemia,” it comes as a big shock to them. Cancer is also associated with drastic changing – life-changing experiences. Patients think about their shortened life span, and the difficulties they’ll have to endure in this shortened life span due to the treatments they will be needing for their cancer. But I want to tell my patients that even though they have a leukemia, they have a cancer, they can still focus on their life in general. 

They have – this has been made possible by very effective yet gentle treatments approved for CLL. Patients can have an enjoyable, fulfilling life focusing on their life in general, and thrive. 

Katherine:

Thank you for that, Dr. Bhat. That’s important for patients to know. Let’s move on to treatment and walk through CLL treatment classes and types. Some of our audience members may already know this information, but it’s a good baseline for newly diagnosed patients. First, CLL patients are often put in “watch and wait” when they’re first diagnosed. What does that mean? 

Dr. Bhat:

So, “watch and wait” means observation. CLL is a slow-growing cancer, generally, and one of the few cancers that’s managed by observation if it’s not causing any problems to the patient. These problems could include symptoms in the form of fatigue, unintentional weight loss, symptomatic enlargement of their lymph nodes or spleen, or we could see changes in their blood work in the form of decreased hemoglobin or decreased platelets. 

If this is not happening, observation is still the standard of care. And data from this comes from a number of clinical trials where patients were treated based on just having the disease without having any of the symptoms or signs I just mentioned. 

All these studies had negative results, meaning that starting treatment at diagnosis did not affect the overall survival of these patients. These patients – these studies were, however, done in chemoimmunotherapy era. Now, we have targeted agents. And also, now we are able to define CLL better, which means that we are able to predict who has higher risk disease. 

So, there’s renewed interest in these – what these are called, early intervention studies. But until we have those results are matured and available, “watch and wait” is still the standard approach. And during “watch and wait,” we see patients at regular intervals, we assess them for symptoms, we look at their bloodwork, and one of the main reasons for seeing these patients at regular intervals is to reinforce what symptoms we want them to pay attention to. So, educating patients at each visit is a very important part of these visits. 

“Watch and wait” may be all that 1/3 of our patients may need through their lifetime. They may never need any CLL-directed treatment. 

Katherine:

Dr. Bhat, when it’s time to start therapy, what types of treatments are available for CLL patients? 

Dr. Bhat:

So, when we think about treatment for cancer, we think about chemotherapy – the conventional chemotherapy that’s associated with side effects like hair loss, nausea, or vomiting. I’m very happy to say that conventional chemotherapy is no longer the standard of care for patients with CLL. Patients who need treatment for CLL are nowadays treated with what are called, “targeted agents.” 

And we have, in general, two different classes of targeted agents that have been approved for treatment for CLL. We have the BTK inhibitors, Bruton’s tyrosine kinase inhibitors, of which we have three. We have ibrutinib (Imbruvica), we have acalabrutinib (Calquence), and we have zanubrutinib (BGB-3111). Then we have BCL-2 inhibitors, of which we currently have one approved, of which is called venetoclax (Venclexta). These treatments can be combined with monoclonal antibodies, which are directed towards the antigen called CD20. For example, rituximab (Rituxan) or obinutuzumab (Gazyva). 

Typically, venetoclax is combined with monoclonal antibody as a time-limited therapy. BTK inhibitors usually are not combined with monoclonal antibody. 

Katherine:

What about stem cell transplant, does that fit in there? 

Dr. Bhat:

So, stem cell transplant still has a role for treatment of patients with CLL, but it has moved down the line with such highly effective and well-tolerated oral agents available. 

But, for refractory patients – what we call dual-refractory patients, we definitely are, especially in high – patients who have higher risk features, we do refer them to stem cell transplant. 

Katherine:

And what is a dual-refractory patient, exactly? 

Dr. Bhat:

Dual-refractory patients mean patients who have had a BTK inhibitor, be it ibrutinib, acalabrutinib, or zanubrutinib, and the disease has progressed on that. And then we give them venetoclax, which is a BCL-2 inhibitor. So, these are the two classes of targeted agents that we have available. If they have received ibrutinib, acalabrutinib, or zanubrutinib, and after that, a venetoclax, or venetoclax followed by a BTK inhibitor, and the disease has progressed on both. These patients are called dual-refractory, and currently they tend to be very resistant to whatever treatments we have available. And we looked at other modalities of treatment, be it clinical trials or stem cell transplants for that. 

Katherine:

How are targeted therapies administered? 

Dr. Bhat:

So, most of the targeted therapies that we have, we are happy to say that these are oral agents. The BTK inhibitors, the three that we have available, are oral agents. Ibrutinib is taken once a day, zanubrutinib and acalabrutinib are twice a day. Venetoclax, similarly, is an oral agent and is taken once a day. Monoclonal antibodies are also considered targeted agents. These are given as infusions in the clinic or in the clinician’s office.  

Katherine:

The oral medications, patients take that at home? They don’t have to go into the hospital? 

Dr. Bhat:

They do not have to go into the hospital. However, venetoclax is associated with a specific side effect called, “tumor lysis syndrome,” where this medication works so well that initially the cells with die off quickly and then things can collect in the blood.  

For example, uric acid can go up, electrolytes can be up, any number can go up. So, we monitor what those initial weeks of starting venetoclax, we monitor patients very closely. We have them come back and forth to the clinic for monitoring, bloodwork, maybe hydration. And sometimes, if we think they’re at a very high risk for this tumor lysis syndrome, we admit them to the hospital.  

Dr. Bhat:

After we cross that, those are administered at home. They can take these at home. 

Katherine:

Dr. Bhat, where do clinical trials fit into treatment? 

Dr. Bhat:

So, clinical trials play a very important role to advance treatments. Clinical trials for CLL are done to test new treatments, new combinations of treatments, compare different treatments to each other. The goal of these clinical trials is to continue to do better than what we currently have available. This is how treatments improve. Despite all the advancements that we have had in CLL, in the recent years, it continues to be an incurable disease, even today. Our goal as researchers is never to stop until we get to that cure, and clinical trial is that pathway to that cure.  

Katherine:

Are there emerging therapies that are showing promise?  

Dr. Bhat:

Yes, of course. There are a number of emerging therapies that are showing promise. So, we all know about ibrutinib and other BTK inhibitors. These work very well, but sometimes the disease can get resistant to these medications, meaning that it stops responding to these treatments. We are excited about this new kind of BTK inhibitor called pirtobrutinib which has shown great promise in these resistance cases, and we are hopeful that it’ll be approved soon. 

Katherine:

Are there other options that patients have? 

Dr. Bhat:

So, we all hear about what is called, “chimeric antigen receptor T-cell therapy,” or CAR-T therapy. This is studied under clinical investigation for CLL and looks very promising. The therapy uses the person’s own immune cell called, “T cell” to identify and attack cancer cells. 

T cells are taken from the patient’s blood and sent to a specific lab. There, the cells are modified so that they can better find and attack cancer cells. These modified T cells are then re-injected back into the patient to find and fight that cancer, to eradicate the disease. So, this looks very promising. 

Katherine:

Many CLL community members are interested in learning more about their disease. So, for newly diagnosed patients, what are a few educational resources you recommend to help them learn more about their condition? 

Dr. Bhat:

There are a number of well-established support groups or educational resources for our patients. These include the CLL Society, The Leukemia & Lymphoma Society, Lymphoma Research Foundation, and then we have Patient Empowerment Network, and we have Patient Power. All these resources provide support groups, organize webinars, and have educational material for our patients. 

Katherine:

What about patients who have been living with CLL for many years, or are quite knowledgeable about their disease? Are there more advanced resources for patients to stay up to date on the latest research and treatment? 

Dr. Bhat:

So, for patients who want to search for additional resources, especially looking for clinical trials, going on this website called clinicaltrials.gov, they can first search for CLL-related clinical trials. Also, NCCN, or “National Comprehensive Cancer Network,” has patient resources for each disease, and then they can find information on CLL there, also. I would also like to say that Google is a good resource, as long as you know where it is taking you. 

Katherine:

Exactly. You may not be able to rely on everything you find. 

Dr. Bhat:

Right.  

Katherine:

Yeah. Many people with CLL will experience fear and anxiety, whether it’s the stress of being in “watch and wait” or worrying about regression. Why do you feel it’s important for patients to share how they’re feeling with their healthcare team? 

Dr. Bhat:

So, one of the important things to know about CLL is that CLL, at this point of time, it’s not a curable disease. It is a lifelong disease. Patients will have to deal with CLL for the rest of their life in some form or other, either on watchful waiting, or on active treatment, or if they’ll complete a treatment, they’ll have this lurking fear of relapse at any time. A large part of what I do is to help my patients understand what it means to live with CLL. And, of course, anxiety is a big part of that living with CLL. 

Although at this time, we’re unable to cure our patients with CLL, I want my patients to understand that it’s very treatable, treatments are very well-tolerated with low toxicity, and patients live a long life. They can have good, productive, and active life. They should ask their care team about resources for social, emotional, and physical support. 

They should let them know about their concerns, talk about their feelings. 

Katherine:

That’s my next question, actually. How can a social worker provide support and are there other healthcare team members who might be able to help? 

Dr. Bhat:

So, yes, patients are on a rollercoaster – emotional rollercoaster with this diagnosis. With this diagnosis come lots of unknowns. Worries about possible shortened life span, anxiety over treatment, and effects of treatment. So, there’s lots to deal with, and lot of uncertainty, which causes a feeling of hopelessness for these patients. So, psychological support is very important. That’s where the role of social worker comes in. 

We get them involved to help patients deal with the diagnosis, and social workers – they can provide patients with tools to cope with this life-changing event. They use life tools like encouraging positive thinking, mindfulness, being aware of what the patient can control involving faith and family, and also involving self-care. 

That’s where we see the role of the whole team as such. If patients are having more difficulties, we can have other members of a team, like a mental health provider, connect with our patients. Social workers and other members of the team can help our patients get connected to support groups, or even to other patients who have had similar experiences. 

Katherine:

What about worry and anxiety related to COVID and compromised immunity? What would you like patients to know? 

Dr. Bhat:

So, COVID has become another source of anxiety, unfortunately, for many of our patients, and rightly so. Our patients with CLL are considered immunocompromised, meaning that their immune systems do not work that well, which makes these patients very susceptible to different kinds of infections, COVID being one of them. And this was actually shown by some of the early COVID-related studies that showed a very high mortality in patients with CLL. 

This has improved now, mostly because now we are better equipped to handle COVID. We have COVID-directed medications available, but the major impact has been made by the vaccines. So, we highly encourage our patients to get vaccinated against COVID and keep up to date with the latest CDC guidelines. Also, we have Evusheld available, which is under emergency use authorization, and our patients with CLL, due to their weaker immune system, are eligible to get this, which adds an extra layer of protection for our patients. 

Also, it’s important to know that our test – if our patients test do test positive for COVID, they should let their team of doctors know immediately, since now we have monoclonal antibodies and pills that can be used to treat symptomatic COVID. 

Katherine:

That’s great information, thank you. Financial concerns can be another source of stress for people with CLL. Obviously, everyone’s situation is different, of course, but what resources are available for patients who need financial support?  

Dr. Bhat:

So, financial barriers can be a real concern for our patients. Targeted therapies are very expensive, and although insurances do cover them, the approved FDA drugs, copays can be very high, and this adds on because our patients with – our treatments with CLL, some of them tend to be indefinite. That means patients have to take those medications on an ongoing basis, and when they face such situations, high copays, we look into financial assistance. We look for funding for copay assistance, and funding can be provided by pharmaceutical companies. We can also apply for grants through The Leukemia & Lymphoma Society and other resources to help out our patients with these financial concerns. 

Katherine:

So, does the patient work with the healthcare team to find financial support? 

Dr. Bhat:

Absolutely. We at our institution have what is called, “MAP,” or Medication Assistance Program. 

And when we see that – we run the medications through the insurance, then we see the copay is high, we refer our patients to the MAP program, and then they take over. They find them grants, they find them assistance through be it pharmaceuticals, copay assistance programs. So, invariably, almost all patients who come and see us are helped through that program.  

Katherine:

What about a nurse navigator or patient navigator? What do they do? How can they help? 

Dr. Bhat:

Well, so yes. Nurse navigators and patient navigators are also very important for caring for our patients. So, patients can have, besides our care for our patients which includes caring for their disease, caring for their symptoms, caring for their reduced hemoglobin and reduced platelets, our symptom management, they have psychological needs, they have functional needs, they have needs like family support.  

So, these are all the things that patient navigators can help patients set that up based on their – we have patients who travel from out of state, are from two or three hours away. So, these patient navigators look into what resources they should have available locally. Sometimes, patient navigators help us – some patients cannot do frequent travels back and forth, so we get them connected to local oncologists, also. So, patient navigators look into those appointments, look into those offices, so they provide a lot of help to us manage our patients. So, they provide more of a holistic management, rather than just treatment of CLL. 

Katherine:

Let’s answer a few audience questions that we received in advance of the webinar. This one is from William. 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, the pirtobrutinib, 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. 

Katherine:

Here’s another question from Anna. She asks, “What is MRD, and does that mean that the disease is cured?” 

Dr. Bhat:

So, MRD is minimal residual disease, and in CLL is defined as the number of leukemic cells that can be detected in the blood or bone marrow following treatment, meaning how many cancer cells are remaining after treatment? This can be checked by a couple of tests. Most commonly, we use flow cytometry. Undetectable MRD is currently defined as the presence of less than one cell – one CLL cell in 10,000 white cells. 

It’s emerging as an endpoint in a number of clinical trials, and presence of no MRD, also called, “MRD-negative status,” although not considered a cure, predicts better outcomes with longer remission. This is being done in combination treatment, and although it’s part of clinical trials currently, with more data available, we may start using this in clinical practice in the next coming years. 

Katherine:

Sophia wants to know, “Are there any clinical trials regarding Richter’s, or DLBCL, transformation?” 

Dr. Bhat:

So, Richter’s transformation means when CLL, which is a low-grade disease, changes into high-grade lymphoma, and most commonly it’s “diffuse large B-cell lymphoma,” or DLBCL. Currently available treatments for Richter’s transformation are, unfortunately, sub-optimal. So, clinical trials to find better treatments are critical for this division, and there are a number of these currently going on. For example, some trials add targeted agents to the backbone of standard chemotherapy called, “R-CHOP.” 

So, we have one trial where acalabrutinib is being added. There’s another clinical trail where venetoclax is being combined with R-CHOP. One of the problems with Richter’s Transformation is that it tends to be refractory to treatment, and it tends to come back or relapse. So, there are studies ongoing for relapse treatment as well, with combination of targeted agents. And CAR-T therapy, we just talked about that, is also being studied in Richter’s Transformation. So, there’s a lot going on to improve the outcome for this. 

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. 

Katherine:

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

Dr. Bhat:

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

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

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

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

Katherine:

Thank you, Dr. Bhat, for all the information. And please continue to send in your questions to question@powerfulpatients.org, and we’ll work to get them answered on future programs. Dr. Bhat, as we close out our conversation, I’d like to get your thoughts on where we stand with CLL progress. Can patients truly thrive with CLL? 

Dr. Bhat:

So, we have made strides in CLL treatment in the past 10 years that really changed the lives of our patients. These treatments work extremely well, and the side effects are gentler than what we used to see with conventional chemotherapy. And it’ll continue to get better with ongoing research, so I will tell our patients to focus on their lives. We know that they have this disease, but we know how to control it well. So, live your life. Enjoy. Be assured that we have all the tools available for you so that you can thrive. 

Katherine:

Yeah. It seems like there’s a lot of hope in the field. Thank you so much for joining us today, Dr. Bhat. It’s been a pleasure. 

Dr. Bhat:

Thank you so much for having me. 

Katherine:

And thank you to all of our partners. To learn more about CLL and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us today. 

Tools for Choosing the Right Prostate Cancer Treatment Approach

Tools for Choosing the Right Prostate Cancer Treatment Approach from Patient Empowerment Network on Vimeo.

Dr. Rana McKay discusses the factors that impact advanced prostate cancer treatment decisions. Dr. McKay reviews potential treatment side effects and explains how patients in treatment are monitored.

Dr. Rana McKay is a medical oncologist at UC San Diego Health and an associate professor in the Department of Medicine at the UC San Diego School of Medicine. Learn more about Dr. McKay, here.
 
 

Related Resources:

What Is Personalized Prostate Cancer Medicine?

Tools for Partnering in Your Prostate Cancer Care


Transcript:

Katherine Banwell:

Since prostate cancer affects men differently, let’s review what factors could impact which treatment is right for their individual disease. How about we start with symptoms? 

Dr. Rana McKay:

So, yeah. I mean absolutely. I think symptoms are definitely something that plays into effect. Sometimes when patients are first diagnosed, they may not have symptoms. But, you know, boney pain, symptoms of urinary obstruction. You know, there’s specific treatments and strategies that we can deploy to help with those kinds of things. You know other factors that I think I – we take into account when we’re making decisions about which agent should any one patient receive is where are their sites of metastases? Is there disease just in the bones and lymph nodes or are there other organs involved? What’s the genomic make-up of the tumor? There are certain treatments that we would utilize if someone had a certain specific you know, genetic make-up for their tumor. You know, other things that are really important are what kind of drugs has the patient seen before or has that tumor been exposed to? Because that also helps us strategize for what to give them in the future.  

Katherine Banwell:

Do you take into consideration the patient’s comorbidities and their age and overall health? Things like that?  

Dr. Rana McKay:

Absolutely. Yeah. I think we need to absolute take that in account. I think – I think age is one thing. But I think functional status is just as – as important as the actual number itself because people are very different regarding the things that they can do at various age limits and so, that absolutely takes into account weighing the side effects of any given therapy and how that may interact with someone’s existing comorbidities and it may be something that we have to work with a team of other doctors to basically make sure that there is comprehensive, well-rounded care for any one patient.   

For example, some therapies may increase the risk of hyper-tension or increase the risk of volume overload. And so, if somebody has issues with that already we may have them see a cardiologist so we can make sure that, you know, we’re kind of addressing the totality of the patient experience. 

Katherine Banwell:

What do you mean by volume overload? 

Dr. Rana McKay:

Volume overload, I mean if they’ve got too much fluid on board. So, maybe if they have heart failure or something like that, and we have a therapy that’s going to cause them to retain fluid. And so then, we would have to work with a cardiologist to make sure that they don’t run into issues 

Katherine Banwell:

Mm-hmm. Once a man is undergoing treatment for advanced prostate cancer, how are they monitored to see if it’s actually working? 

Dr. Rana McKay:

So, a lot of ways. So, one is by just, you know, visiting with the patient. Making sure that their symptoms are in check. Making sure that they’re not developing new aches or pains that are worrisome. It’s by checking their labs in addition to their organ and bone marrow function. We would check their PSA. And PSA isn’t the whole story. But it is one factor that contributes to us determining whether treatment may or may not be working. It’s also doing intermittent scannings. So, you know, CT scans of the organs, of the lymph nodes. Bone scan and now we actually have PSMA based imaging, which can be integrated to help assess where the disease is and not yet being utilized to assess whether something is working, because we haven’t really defined the criteria there. But, it can be utilized as well.  

Managing the Side Effects of Advanced Prostate Cancer Treatment

Managing the Side Effects of Advanced Prostate Cancer Treatment from Patient Empowerment Network on Vimeo.

Prostate cancer expert Dr. Rana McKay reviews potential prostate cancer treatment side effects and discusses strategies for managing these issues.

Dr. Rana McKay is a medical oncologist at UC San Diego Health and an associate professor in the Department of Medicine at the UC San Diego School of Medicine. Learn more about Dr. McKay, here.
 
 

Related Resources:

What Is Personalized Prostate Cancer Medicine?

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Tools for Choosing the Right Prostate Cancer Treatment Approach


Transcript:

Katherine Banwell:

Dr. McKay, for these treatment classes, what can patients expect as far as side effects? 

Dr. Rana McKay:

Absolutely. So, I think side effects – discussing side effects is a really important part of the discussion for selecting any one given therapy and in general, I think when we talk about the hormonal therapies one of the side effects that people can get is largely fatigue.  

But a lot of the symptoms are related to low testosterone. And so, that may mean muscle loss, bone loss, you know, hot flashes, fatigue, decrease libido. So, you those are things to consider with hormonal therapies. With the chemotherapies, I think the big ones we worry about are fatigue, risk of infection, blood counts dropping a little bit, people getting tired, numbness and tingling in the hands and feet can occur, some swelling in the legs are common side effects for chemotherapy agents. With regards to the immunotherapy with the vaccine therapy, it actually tends to be a fairly well tolerated treatment. Maybe some fatigue, rarely some dizziness or some lip – lip sensitivity, numbness with the – the process of kind of collecting the cells. But it actually tends to be fairly well tolerated.  

The targeted therapies can cause fatigue. They can cause the blood counts to drop and can impact bone marrow function. There can be sometimes GI side effects. Nausea, rash, and then the immune therapy, the pembrolizumab (Keytruda), that is FDA-approved sometimes that can cause immune related adverse events which is kind of over activation of the immune system developing you know, what I’d call it as the itises. Colitis or pneumonitis which is inflammation of various organs and symptoms related to wherever that may be.  

What Is Advanced Prostate Cancer?

What Is Advanced Prostate Cancer? from Patient Empowerment Network on Vimeo.

When is prostate cancer considered advanced? What are the symptoms? Expert Dr. Rana McKay explains.

Dr. Rana McKay is a medical oncologist at UC San Diego Health and an associate professor in the Department of Medicine at the UC San Diego School of Medicine. Learn more about Dr. McKay, here.
 
 

Katherine Banwell:

What does it mean for prostate cancer to be considered advanced? 

Dr. Rana McKay:

So, generally what that means is that the cancer may have spread outside of the body – outside of prostate to other parts of the body such as the bone or the lymph nodes which is a common location where prostate cancer can go. Additionally, it may mean that the cancer may have come back after it was initially treated with an intent to cure a patient. But then you know the PSA demonstrates, that you know, there’s a rise in the PSA, and the cancer is recurrent.  

Katherine Banwell:

Right. That makes sense. What are the common symptoms of advanced prostate cancer?  

Dr. Rana McKay:

So, you know, I would probably say there common symptoms and just because somebody has these symptoms doesn’t mean they have prostate cancer. But fatigue, weight loss, urinary symptoms, trouble urinating, you know, benign prostatic atrophy is one of the most common symptoms or most common conditions in men and –  

Katherine Banwell:

What does that mean?  

Dr. Rana McKay:

So sort of benign enlargement of the prostate. You know that’s a common phenomenon that happens with age, and it can affect somebody’s ability to urinate. 

But, you know sometimes with prostate cancer it can also impact somebody’s ability to urinate. Their stream, their flow. They may have rectal discomfort. They may feel tired, boney pains. Usually, I tell patients you know persistent progressive symptoms that are just, you know, not going away, not getting better. Those need to be looked at by a physician to evaluate further. 

What Are Common Side Effects of DLBCL Treatment?

What Are Common Side Effects of DLBCL Treatment? from Patient Empowerment Network on Vimeo.

Lymphoma expert Dr. Matthew Matasar reviews common side effects of diffuse large B-cell lymphoma (DLBCL) treatment.

Dr. Matthew Matasar is a lymphoma expert at Memorial Sloan Kettering Cancer Center and Chief of Medical Oncology at Memorial Sloan Kettering Bergen. To learn more about Dr. Matasar, visit here.

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Transcript:

Katherine Banwell:

What are common side effects of DLBCL treatment approaches? 

Dr. Matasar:

Like anything, the side effects are dependent upon the treatments that we use. So, treatments that use chemotherapy-based approaches will often have the side effects that we associate with chemotherapy. And obviously not all chemotherapies are created equally. But treatments like R-CHOP or R-CHP-pola, or Polarix regimen, these are treatments that use traditional cytotoxic chemotherapy agents and anthracycline based chemotherapy that have well-characterized side effects that are unfortunately unavoidable but often temporary things like hair loss.  

And hair loss is unavoidable with these treatments although temporary.   

The Oncovin or polatuzumab treatments can lead to a problem called neuropathy, which can manifest as numbness or tingling in the fingers or toes or constipation because our intestines have nerves too that are affected by these treatments. Certainly fatigue and lowering of the immune system are common with these and other chemotherapy medicines as well. And your doctors will always talk to you about ways to reduce the risk of infection such as vaccination and such as anti-infective medicines or immune boosting medicines to try to limit the risk of infection while receiving such treatments.  

What Do You Need to Know About CLL Treatment Side Effects?

What Do You Need to Know About CLL Treatment Side Effects? from Patient Empowerment Network on Vimeo.

CLL Expert Dr. Jean Koff discusses common side effects of CLL treatment and explains how they can be managed.

Dr. Jean Koff is an Assistant Professor in the Department of Hematology and Oncology at Winship Cancer Institute of Emory University. Learn more about Dr. Koff, here.

See More from Thrive CLL

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Transcript:

Katherine Banwell:

What are the common side effects of treatments, and how are they managed? 

Dr. Jean Koff:

So, each of the different classes of agents has a different profile of side effects. The BTK inhibitors, the first class that I mentioned with ibrutinib (Imbruvica) and acalabrutinib (Calquence), are usually very well tolerated. The most common side effects that we tend to see are things that the patients can feel or see, but also things that we can see on the labs when we’re monitoring patients. So, sometimes you can see a lower platelet counts or lower blood cell counts with ibrutinib. That’s something that you may not notice, but your doctor’s going to notice on the – the blood counts when you come to the office. Sometimes ibrutinib can cause a rash or GI upset, this is usually easily managed with supportive care from your physician.  

And then some more – some more common effects of the BTK inhibitors include joint pain and headache. And again, many physicians, because we’ve been using BTK inhibitors for a long time, have a good regimen for treating these side effects. More uncommon side effects of BTK inhibitors, particularly ibrutinib that we look out for would be abnormal heart rhythms and some tendency for bleeding. But these are relatively uncommon and with newer BTK inhibitors, we’re seeing lower rates of these side effects.  

Dr. Jean Koff:

So, in terms of venetoclax side effects we have a little bit of a different profile. This agent is much more likely to cause lower cell counts, especially in a white blood cell count known as neutrophil count, and so your doctor will be monitoring you for that. In terms of patient side effects that you can feel, it can cause a rash, it can cause some GI upset. These are usually relatively easily managed but we want you as the patient if you’re on venetoclax to talk to your doctor about these side effects so that they can help you feel better and help you manage those. In terms of the anti-CV20 monoclonal antibodies, which we use a couple in CLL more frequently, they have very similar side effect profiles.  

So, one is rituximab, and one is obinutuzumab. Obinutuzumab is usually used in combination with venetoclax in front-line CLL.  

Like I mentioned before, this is an infusion and most of the side effects that we think about and most commonly see in these anti-CV20s are side effects that patients have during the infusion. And these are referred to as infusion reaction. And these are relatively common, around 30 percent in these anti-CV20 monoclonal antibodies. So, what is an infusion center react – er sorry, what does an infusion reaction look like? This looks sort of like an allergic reaction. 

Katherine Banwell:

Hm. 

Dr. Jean Koff:

So, your nurses in the infusion center are going to be monitoring you very carefully once you start the infusion, and they’re going to start it at a low dose, very slowly. But the side effects they’re monitoring for, they’re looking for changes in your heart rate or blood pressure. You may start to feel hot or cold or sweaty, you may have chills. Sometimes patients can have swelling in their throat or their tongue. And what will happen is because these are fairly common, is we’re still able to give the anti-CV20, but what we do is the nurse will stop the infusion, they may give you some medications that calm down that infusion reaction. So, medications like antihistamines –  

Katherine Banwell:

Mm-hmm.  

Dr. Jean Koff:

Or steroids that help tamp down that immune response, and then they start the anti-CV20 infusion at a lower rate. The vast majority of patients will be able to receive an anti-CV20 antibody even if they have an infusion reaction. They may just need a little bit more of those immune tamping-down medications like antihistamines and steroids. And then the last thing to consider, which I think we’ve mentioned, especially in the venetoclax-containing regimens, is the tumor lysis syndrome. And so, that is a side effect like we mentioned is kind of like the venetoclax working really, really, really well, of the tumor breaking down too quickly.  

And so, patients who have tumor lysis, if they’re at high-risk, hopefully they’re already being monitored very closely with frequent lab draws, and they may receive medications that – that diminish the risk of adverse events happening because your electrolytes are out balance, for instance, your potassium is too high, or your calcium is too low. Because your doctors are monitoring you closely, they can give you medications that can help balance  out those – those electrolytes and help protect the kidneys. The tumor lysis is typically not a risk after the initial doses of venetoclax.  

So, the first couple weeks is when we typically monitor that, and then once the CLL has been broken down, or as I like to say, once it’s been cooled off a little bit, then you no longer have this risk of tumor lysis and it – it doesn’t require further monitoring. 

Katherine Banwell:

That’s great information, thank you.  

How Are CLL Symptoms Treated?

How Are CLL Symptoms Treated? from Patient Empowerment Network on Vimeo.

Dr. Jean Koff reviews common CLL symptoms and explains why patients should discuss any issues they experience with their healthcare teams.

Dr. Jean Koff is an Assistant Professor in the Department of Hematology and Oncology at Winship Cancer Institute of Emory University. Learn more about Dr. Koff, here.

See More from Thrive CLL

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Transcript:

Katherine Banwell:

One part of thriving with CLL is managing the symptoms of the disease. What are the common symptoms of CLL? 

Dr. Jean Koff:

So, one thing that I see with nearly all of my CLL patients, regardless of where they are in the CLL journey, and regardless of whether they need active medications to manage their CLL, is some degree of fatigue. And this can range from just mild fatigue that patients notice that they need a little bit of a breather in the middle of the day, to needing more sleep at night, to not being able to exercise as much as they’re used to. And that is by far one of the most common symptoms we see. Again, whether or not their disease needs medication to manage it.  

The classic symptoms of CLL that often let us know that it’s time to start medical management are not just this fatigue. But the classic symptoms are  B symptoms. And we describe those as fevers, night sweats, and unintentional weight loss. Those are very common. And then some patients with CLL will also have what we call palpable lymphadenopathy, which is our term for lymph nodes that are enlarged that you can feel. And the most common places to feel these on the body are on the neck, under the arms, and in the groin.  

Katherine Banwell:

Okay. How are symptoms treated? 

Dr. Jean Koff:

So, if your symptoms progress to the point that your doctor thinks you need medication – they’re becoming disruptive to your life, or they are getting worse and worse over time, then there are a variety of medications that we can use in CLL. And this is actually a very exciting field. Right now, the state of the field is that most patients who are starting on their first treatment for CLL will use some sort of oral medication, and that may be accompanied by an IV – what we call monoclonal antibody, or it may not. But one thing that has really changed even since I very first started practicing, is that we no longer commonly use what I would call conventional chemotherapy to treat CLL – even though this was the standard of care just a few years ago. 

Katherine Banwell:

Wow. So, a lot has changed. 

Dr. Jean Koff:

Yes, definitely. 

Thriving With Prostate Cancer: What You Should Know About Care and Treatment

What does it mean to thrive with advanced prostate cancer? Dr. Rana McKay discusses the goals of advanced prostate cancer care, reviews current and emerging treatment options, and shares advice for playing an active role in healthcare decisions.
 
Dr. Rana McKay is a medical oncologist at UC San Diego Health and an associate professor in the Department of Medicine at the UC San Diego School of Medicine. Learn more about Dr. McKay, here.
 
 

Katherine Banwell:    

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to focus on how patients can aim to live and thrive with advanced prostate cancer. We’re going to discuss treatment goals and the role patients can play in making key decisions. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well let’s meet our guests today. Joining me is Dr. Rana McKay. Dr. McKay, welcome. Would you please introduce yourself?

Dr. Rana McKay:     

Of course. Thank you so much for having me. My name is Rana McKay and I’m a GU medical oncologist at the University of California San Diego.  

Katherine Banwell:    

Excellent. Thanks so much for taking time out of your schedule to join us. Since this webinar is part of PEN’s Thrive series, I’d like to ask you from your perspective, what do you think it means to thrive with advanced prostate cancer?

Dr. Rana McKay:        

That’s a very good question and I think that’s what um, a lot of patients want to actually you know, do in their day-to-day existence. I think it means that they are combatting their disease. They’re taking a proactive role in um, you know, uh tackling um, their illness. They um, are uh, attentive to sort of doing the activities of daily living that really bring them joy and satisfaction and happiness and setting up a treatment plan that is a mutually agreed upon treatment plan with their clinician. That they have buy-in on. That their caregivers have buy-in on. That allows them to do the things that they love to do while keeping their cancer at bay.

Katherine Banwell:    

Okay. Thank you for sharing your insights. Before we move onto treatment, I mentioned that this webinar is focused on advanced prostate cancer. What does it mean for prostate cancer to be considered advanced?

Dr. Rana McKay:        

So, generally what that means is that the cancer may have spread outside of the body – outside of prostate to other parts of the body such as the bone or the lymph nodes which is a common location where prostate cancer um, uh, can go. Additionally, it may mean that the cancer may have come back after um, it was initially treated with an intent um, to cure um, a patient. But then you know the PSA demonstrates um, that you know, there’s a rise in the PSA and the cancer is recurrent.

Katherine Banwell:    

As you mentioned uh, appropriate treatment is part of thriving. We’re going to talk about treatment approaches. But first, how would you define treatment goals?

Dr. Rana McKay:       

So, you know when I look at defining treatment goals it’s focusing on what do we wanna achieve from the standpoint of the cancer? Meaning, you know, what are objectives that are associated with patients living longer?

And then what are objectives um and strategies that we can set-up to make sure that patients are living better? So, I think the treatments are basically set-up to basically help you achieve those two goals. What can we do to help you live longer and feel better?

Katherine Banwell:    

Yeah. Well, let’s walk through the types of treatments that are used today to treat advanced prostate cancer. What are the treatment causes and who are they appropriate for? Let’s start with surgery, for instance.

Dr. Rana McKay:       

So, surgery is something that’s utilized uh, early on when people are diagnosed with cancer. It tends to be utilized when the cancer has not necessarily spread to other parts of the body but is still localized within the prostate itself or maybe there’s just some little bit of breakthrough in the capsule. Sometimes it can be used in people who have involvement of the prostate cancer in the lymph nodes. But it’s generally not utilized in people who have cancer that’s spread to other parts of the body.

Katherine Banwell:    

Mm-hmm. What about other treatment classes? What are they?

Dr. Rana McKay: 

So, radiation can also be utilized. Radiation is a treatment modality that can be used for people with localized disease and um, also it can be utilized for people with advanced disease to treat the primary tumor.

Additionally radiation therapy can be used to help treat symptoms um, if there’s a bone lesion causing pain or other areas that are causing discomfort. Sometimes radiation to those areas um, can um, mitigate pain. When I think about the treatment classes for prostate cancer um, they generally break down into several categories. The first um, um, most predominant category is the hormonal therapy category. Hormonal therapies are really the backbone of treatment for men with prostate cancer and they include the more traditional hormonal therapies that really work to just drop testosterone. So, just LRH – L – LRHA agonists and antagonists and also, they include um, newer hormonal therapies in the form of pills that really target um, strategies at also affecting testosterone function and testosterone production. Another class is also the chemotherapy agents. There are two FDA approved chemotherapies for prostate cancer that are life prolonging and um, uh there’s a certain role for uh, chemotherapy for people with advanced disease.

There’s also immunotherapy that can be utilized. Um, there’s a um, uh, vaccine therapy that’s actually one of the first uh, FDA vaccines for any solid tumor that’s proving in prostate cancer that can be utilized. There’s also radio pharmaceuticals.

So, these are specific agents that deliver um, a bits of radiation to specific areas. Whether it be radium 223 which targets the bone or the newest radio pharmaceutical, which was approved called uh, lutecium PSMA that um, basically delivers beta-radiation to little – sites of PSMA expressing cancer cells and the last category that I would highlight is the category of targeted therapy. There are uh, two targeted therapies for prostate cancer for patients who have like genomic alterations. Those include the drugs olaparib and rucaparib. So, as you can see there’s a wide spectrum of drugs that can be utilized to really keep this disease at bay.  

Katherine Banwell:    

Dr. McKay, for these treatment classes, what can patients expect as far as side effects?

Dr. Rana McKay:       

Absolutely. So, I think side effects – discussing side effects is a really important part of the discussion for selecting any one given therapy and in general, I think um, when we talk about the hormonal therapies one of the side effects that people can get is largely fatigue.

But a lot of the symptoms are related to low testosterone. And so, that may mean muscle loss, bone loss, um, you know, uh, hot flashes, um, fatigue, decrease libido, um… So, you those are things to consider with hormonal therapies. With the chemotherapies, I think the big ones we worry about are fatigue, risk of infection, um blood counts dropping a little bit, people getting tired, numbness and tingling in the hands and feet can occur, some swelling in the legs are common side effects for chemotherapy agents. With regards to the um, uh, immunotherapy with the vaccine therapy, it actually tends to be a fairly well tolerated treatment. Maybe some fatigue, rarely some dizziness or some lip – lip sensitivity, numbness with the – the process of kind of collecting the cells. But it actually tends to be fairly well tolerated.

The um, targeted therapies can cause fatigue. They can cause the blood counts to drop and can impact bone marrow function. There can be sometimes GI side effects. Nausea, um, rash, um and then the immune therapy, the pembrolizumab, that is FDA approved sometimes that can cause immune related adverse events which is kind of over activation of the immune system developing you know, what I’d call it as the itises. Colitis or pneumonitis which is inflammation of various organs and symptoms related to wherever that may be.

Katherine Banwell:    

When should a patient consider a clinical trial as a treatment option?

Dr. Rana McKay:        

So, I generally think that a patient should consider a clinical trial at almost every juncture that a – a clinical decision is being made. I think sometimes there’s this misperception that, “Oh. Clinical trials should only be utilized when I don’t have any other options.” Where in fact I would say clinical trials should be an option to discuss every single time a treatment is being changed. Um, because you know the ultimately the goal is to make sure patients are as I said, living longer and living better and um, you know, making sure that clinical trials are an option on the table at every juncture is really a key step in that process.

Katherine Banwell:    

What are the benefits of being part of a clinical trial?

Dr. Rana McKay:       

So, I think there’s a lot of benefits. I think um, you know, uh for patients with advanced disease it may provide access to drugs that they otherwise not necessarily have access to.

Um, so the standard of care therapies you know, we can prescribe those at any juncture. They’re standard of care. But clinical trials um, really offer an opportunity to experiment with a uh, uh another agent um, and doesn’t necessarily take away from the standard of care options.

I think um, the other thing is you know, I think a lot of patients with advanced prostate cancer, they um, they – want to give back to the community. They want to leave a legacy. They want to contribute to the science. They wanna be a part of that mission to make tomorrow better than today for men with prostate cancer and I think participating in clinical trials can really help achieve that goal. Um, and also benefit the individual as well.

Katherine Banwell:    

What about emerging treatments? Are there any that patients should know about?

Dr. Rana McKay:       

Absolutely. So, there’s a lot of treatments that I think are currently undergoing extensive testing.

There’s um, additional uh, targeted therapies um, for example CDK46 inhibitors that are being tested broadly in the um, um hormone resistant space and the newly diagnosed setting. Um, there’s um, also AKT inhibitors. There are other targeted therapies that are being tested. There’s novel hormonal treatments that target resistant pathways like the antigen receptor degraders. There’s a slew of immunotherapy options um, cell therapy, bi-specific antibodies that are also being tested. So, there’s a lot of really exciting and novel treatments that are looking at overcoming resistance for people with advanced disease.

Katherine Banwell:    

Hm. Do you recommend that men with advanced prostate cancer get the COVID vaccines and the boosters?

Dr. Rana McKay:       

Very good question and in general, I do recommend the vaccines. Especially for patients with advanced disease and those that are on therapy. Um, several studies have demonstrated that patients with cancer are at increased risk of having complications related to COVID and particularly patients that are on active treatment with cancer are at even greater riskSo, um, I would definitely recommend vaccination as a preventative strategy to prevent really complications related to COVID.

Katherine Banwell:    

Mm-hmm. Thanks, Dr. McKay. That’s helpful information. Since prostate cancer affects men differently. Let’s review what factors could impact which treatment is right for their individual disease. How about we start with symptoms?

Dr. Rana McKay: 

So, yeah. I mean absolutely. I think symptoms are definitely something that plays into effect.

Um, sometimes when patients are first diagnosed, they may not have symptoms. But, you know, boney pain. Um, Symptoms of urinary obstruction. You know, there’s specific um, uh, treatments and uh, strategies that we can deploy to help with those kinds of things. Um, you know other factors that I think I – we take into account when we’re making decisions about which agent should any one patient receive is where are there sites of metastases? Um, is there disease just in the bones and lymph nodes or are there other organs involved? Um, what’s the genomic make-up of the tumor? Um, there are certain treatments that we would utilize if someone had a certain specific you know, uh genetic make-up for their tumor. You know, other things that are really important are what kind of drugs has the patient seen before or has that tumor been exposed to? Because that also helps us strategize for what to give them in the future.

Katherine Banwell:    

Do you take into consideration the patient’s comorbidities and their age and overall health? Things like that? 

Dr. Rana McKay: 

Absolutely. Yeah. I think we need to absolute take that in account. I think – I think age is one thing. But I think functional status is um, just as – as important as the actual number itself because people are very different regarding um,  the things that they can do at various uh, age limits and so, that absolutely takes into account weighing the side effects of any given therapy and how that may interact with someone’s existing comorbidities and it may be something that we have to work with a team of other doctors to basically make sure that there is comprehensive, well-rounded care for any one patient.

For example, some therapies may increase the risk of hyper-tension or increase the risk of volume overload and so, if somebody has issues with that already we may have them see a cardiologist so we can make sure that um, you know, we’re kind of addressing the totality of the patient experience. 

Katherine Banwell:    

What do you mean by volume overload?

Dr. Rana McKay: 

Uh, volume overload I mean if they’ve got too much fluid on board. So, maybe if they have heart failure or something like that and we have a therapy that’s gonna cause them to retain fluid. And so then, we would have to work with a cardiologist to make sure that they don’t run into issues.

Katherine Banwell:    

Right. That makes sense. What are the common symptoms of advanced prostate cancer?

Dr. Rana McKay: 

So, um, you know, I would probably say there common symptoms and just because somebody has these symptoms doesn’t mean they have prostate cancer. But fatigue, weight loss, urinary symptoms, trouble urinating, you know, benign prostatic atrophy is one of the most common symptoms or most common conditions in men and um –

Katherine Banwell:    

What does that mean?

Dr. Rana McKay: 

Um, so sort of benign enlargement of the prostate. Um, you know that’s a common phenomenon that happens with age and it can affect somebody’s ability to urinate.

Um, but um you know uh, sometimes with prostate cancer it can also impact somebody’s ability to urinate. Their stream, their flow. Um, they may have rectal discomfort. They may feel tired, boney pains. Usually, I tell patients you know persistent progressive symptoms that are just you know not going away, not getting better. Those need to be looked at by a physician to evaluate further. 

Katherine Banwell:    

Mm-hmm. You mentioned genetic mutations. Should patients advocate for genetic testing if they haven’t had it already?

Dr. Rana McKay: 

Um, it all depends on uh, what kind of uh, where they are in the process. So, for most men who have advanced disease, they should undergo genetic testing of both their tumor, and it is also recommended to do hereditary testing for patients who have advanced disease. Um, and that information may not necessarily be utilized at the exact time that the test is done.

But it may be utilized down the road for treatment options at a later time point. Um…

Katherine Banwell:    

Mm-hmm. Once a man is undergoing treatment for advanced prostate cancer how are they monitored to see if it’s actually working?

Dr. Rana McKay: 

So, a lot of ways. So, one is by just you know, visiting with the patient. Making sure that their symptoms are in check. Making sure that they’re not developing new um, aches or pains that are worrisome. It’s by checking their labs um, in addition to their organ and bone marrow function. We would check their PSA. Um, and PSA isn’t the whole story. But it is one factor that contributes to us determining whether treatment may or may not be working. It’s also doing intermittent scannings. So, um, you know, uh, CT scans of the organs, of the lymph nodes. Bone scan and now we actually have PSMA based imaging which can be integrated to help um, assess uh, where the disease is and um, not yet being utilized to assess whether something is working because we haven’t really defined the criteria there.

But um, it can be utilized as well.

Katherine Banwell:    

Mm-hmm. Dr. McKay, how would you define precision or personalized medicine and how close are we getting to personalized medicine for advanced prostate cancer?

Dr. Rana McKay: 

Yeah. So, what I – how I define it is the right treatment for the right patient at the right time. It’s basically you know, based off of somebody’s genomic profile of their tumor and ideally that genomic profiling is done close to the time that that treatment is being initiated. So, within six months or twelve months of somebody starting a given therapy we understand the genetic make-up of the tumor. The tumor has you know, for example a BRCA1 alteration and we know that olaparib is a drug that can be utilized and has demonstrated efficacy for people that have that mutation and then we would use that agent. So, it’s basically trying to um, personalize therapy based on the genomic information of that tumor.

And um, I think we are getting there. There are actually trials now that are being launched that are bio-marker driven trials with bio-marker selected therapies for patients based on -off of not just DNA but also RNA to help with um, allocating a given therapy.   

Katherine Banwell:    

What do you feel are the common obstacles to care for a man with advanced prostate cancer?

Dr. Rana McKay: 

So, I think that there can be a lot of obstacles with regards to um, you know, comprehensiveness of the care. You know it’s one thing to sort of, “Okay. This is the next therapy to treat you with.” But there’s a lot of side effects that can happen with any one given therapy and ensuring that there is open dialogue between um, uh a man and his – his clinician and caregivers.

You know, I think that that can sometimes be a hurdle. Like that open communication can be so important. It’s not just about picking the next best drug but it’s ensuring that there’s sort of comprehensiveness in care. I think a lot of um, you know, patients they may not necessarily know and they’re really kind of dependent on their clinician to sort of go through the compendia of options that may be available and why one may be better than the other for any one given scenario. So, I think it’s like that shared decision-making, that open dialogue.

Um, you know, I think also thinking about advocacy networks, I think um, you know, I can say things until I’m blue in the face like this is what being on ADT feels like. But I think sometimes actually connecting with another patient whose gone through the same experience who can kind of weigh in from the patient perspective like what it actually feels like, I think is not to say a hurdle. But I think we can do a better job as a medical community of making those networking connections available for patients so they can be a part of a broader community of individuals like them going through the same thing they’re going through.

Katherine Banwell:    

Yeah. It helps to know that there are others going through exactly what you’re going through or similar symptoms. We received a patient question prior to the program. What is the difference between my PSA level and Gleason score?     

Dr. Rana McKay: 

Yeah. So, very good question. So, Gleason score is something that is determined based off a pathologic assessment. So, it’s basically you know, a biopsy is done from the prostate or the – the surgical specimen from the removal of the prostate is looked at under the microscope and a Gleason score is based off what something looks like underneath a microscope and ideally, a Gleason score is given really only for the prostate – for tissue derived from the prostate.

So, if somebody has a bone biopsy for example or a lymph node biopsy, they’re not going to necessarily get a glycine score per se. It’s been – been validated from the prostate itself and ideally, also, an untreated prostate. So, if somebody has you know had radiation therapy and then has a biopsy, the Gleason score there is – there should not necessarily be a notation of what a Gleason score is. It’s really an untreated prostate. Now PSA is prostate specific antigen and it’s a protein that’s made from the prostate gland and it’s found in circulation. PSA doesn’t hurt any – the actual you know, molecule itself is – is innocuous. It doesn’t hurt anything. It’s just a marker of um, sometimes can be a marker of burden of disease in prostate cancer and I think sometimes we as clinicians do you know, you know a disservice to some patients because I think we fixate – we can fixate a lot on PSA.

But PSA is not the whole story and it’s one factor of several factors that we take into account in determining whether someone needs treatment or whether a treatment is working or not working.

Katherine Banwell:    

Why should patients feel confident using their voice in partnering in their care? Do you have any advice?

Dr. Rana McKay: 

Um, I mean it’s – it’s absolutely important for patients to share their perspective and for there to be shared decision making at every single juncture along the way. Even around decisions to not treat. So, you know, I think it’s a lot of um – there’s a lot of grays in prostate cancer and a lot of art in deciding what treatment to do and at what specific time and for any given patient given the values that that patient brings to the table, they may come back with a different decision compared to another patient. So, without the patient you know voicing what their values are it’s impossible to make a treatment decision.

So, it is so critically important to have that open communication with your clinician.

Katherine Banwell:    

So, in addition to that – in conjunction with that, should men diagnosed with advanced prostate cancer consider a second opinion or consulting with a specialist?

Dr. Rana McKay: 

I think it’s always a great idea to get a second opinion. Um, you know, I think that um, you know, it will only empower individuals um, when they seek sort of a second opinion to either confirm um what their physician has already told them and then they have reassurance that they’re on the right path or maybe provide some new um, novel insights that they can take into consideration and just think about how that could be applied to them. So, you know, I think that a second opinion is always really valuable.

I will balance that by saying um, sometimes it can be detrimental if there’s lots of opinions because I will say that coming to a consensus when there’s lots of different specialists that are involved, and everybody makes the soup a little bit differently –

Katherine Banwell:    

Yeah.

Dr. Rana McKay: 

Sometimes that I think that can actually um, hurt patients in being able to actually come to a decision because then they’re like, “I don’t know what decision to make. This person said do this. This person said do that. This person said do that.” Um, and so that can sometimes be um, detrimental. But a second opinion, I do always encourage it. I do always value it. But I always want the patient to bring it back to me so I can share with them and discuss, “Okay. I understand. This is why x said X-Y-Z. This still aligns. This still doesn’t.” They need a quarterback like you know, it’s one thing to sort of get second opinions. But I think every man with prostate cancer should have a quarterback that’s driving their care and advocating for them.

Katherine Banwell:    

Yeah. How can patients find specialists near them?

Dr. Rana McKay: 

So, um, I will say that they are national comprehensive cancer institutes. They’re all across the country in rural areas and not. I think um, you know finding the closest NCI designated comprehensive cancer center close to you is probably a good place to start and identifying who is seeing um patients with genetic urinary malignancies or prostate cancer at that facility is a good place. I think the prostate cancer foundation is an excellent advocacy group for patients with prostate cancer. They have a tremendous amount of resources um, to help connect patients with um, clinicians, and other resources um, in their journey with cancer.

Katherine Banwell:    

How can caregivers best support their loved ones?

Dr. Rana McKay: 

So, I think being present is one of the first things. Um, you know, I think that uh, um, you know, uh, being you know, supportive, being present.

Like you know, attending the doctor – doctor’s visits. It doesn’t necessarily have to be every single doctor visit. But those critical doctor visits where um, you know clinical decisions are being made. I think it’s really important also um, to there may be some hesitancy on the part of patients to sometimes be open or vocal with their clinicians about various aspects of what they may be experiencing at home, or they may be undermining or sort of – I think caregivers can help in sort of giving an outsider’s perspective. “Well, this is how things are going at home,” and “You know this is how things are,” and “These are the things that we value and we’re gonna go on this family trip,” and “This is a big-ticket item for us. So, how can we work around planning a treatment plan that allows us to do that?” So, I think it’s really important.

Katherine Banwell:    

ASCO was held in June. Is there news from the conference that patients should know about?

Dr. Rana McKay:        

Yeah. So, I think some of the biggest therapies in prostate cancer that was one of the newest therapies that was just FDA approved is um, Lutetium PSMA. It’s um, a radioligand therapy that targets specifically PSMA expressing cells. Um It delivers a little bit of beta radiation to those cells. Um, that therapy was approved this past Spring and there highlights at ASCO about the utility of this therapy. Um, and again, there’s a series of novel compounds that are being tested in prostate cancer not yet ready for prime time but a lot of exciting work that’s being done um, to try to get new drugs that work better for our patients.

Katherine Banwell:    

Mm-hmm. Going back to ASCO and new developments, how can patients stay informed about research developments like – like these that happen at ASCO.

Dr. Rana McKay:

So, very – very good. I think there’s a lot of networks for people with prostate cancer. I think one like I mentioned, the prostate cancer foundation it’s a wonderful community. Um, that really focuses on making sure that up to date, you know, uh, evidence-based data is uh, distributed to patients in a manner that is – that makes sense. That’s there’s not a lot of medical jargon and so I think that the PCF is really a wonderful resource. Uh, ASCO itself also has um, you know patient interfacing you know, materials through their website.

American Cancer Society does as well. Um, the American Cancer Society can also be a wonderful resource for patients that are newly diagnosed or going through treatment.

Katherine Banwell:    

Mm. Before we end the program, Dr. McKay, I wanted to ask. Are you hopeful that men can thrive with advanced prostate cancer?

Dr. Rana McKay:       

Oh, I am absolutely hopeful that they can thrive. I mean that is um, the name of the game and I think there’s a lot of um, uh, people who can look to for motivation.

Um, uh, to basically show that despite treatment, despite having advanced disease patients can thrive and continue doing all of the things that they love that give them joy and satisfaction in their lives.

Katherine Banwell:    

It seems like there’s a lot of progress and hope in the field which is good. Dr. McKay thank you so much for taking the time to join us today.

Dr. Rana McKay:       

Of course. My pleasure.

Katherine Banwell:    

And thank you to all of our partners. To learn more about prostate cancer and to get tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks so much for joining us today.

Thriving With CLL: Your Role in Managing Your Care

Thriving with CLL: Your Role in Managing Your Care from Patient Empowerment Network on Vimeo.

 How can patients thrive with chronic lymphocytic leukemia (CLL)? Dr. Jean Koff discusses CLL treatments approaches, strategies for managing disease symptoms and treatment side effects, and shares advice on how patients can be proactive in their care.

Dr. Jean Koff is an Assistant Professor in the Department of Hematology and Oncology at Winship Cancer Institute of Emory University. Learn more about Dr. Koff, here.

Download Resource Guide

See More from Thrive CLL

Related Resources:

Setting CLL Treatment Goals WITH Your Team

Expert Advice for CLL Self-Advocacy

Expert Advice for CLL Self-Advocacy

CLL Treatment Approaches: What Are the Types?

Transcript:

Katherine Banwell:  

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss what it means to thrive with CLL. And how you can play an active role in your care. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access information to follow along during the webinar. At the end of this webinar, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today, in order to help us plan future webinars.  

And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please speak to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Jean Koff. Dr. Koff, welcome! Would you please introduce yourself? 

Dr. Jean Koff:

Hi, I’m Jean Koff. I’m a lymphoma and CLL specialist from Emory University and it’s a pleasure to be with you here today. 

Katherine Banwell:

Thank you for taking the time to join us. We start all of our webinar in our CLL Thrive series with the same question. In your experience, what does it mean to thrive with CLL? 

Dr. Jean Koff:

So, I think thriving with CLL means that a patient is informed about their disease, they are comfortable with the physician who’s helping them navigate their disease and their management plan. And their management plan, whatever that might be, is really allowing them to focus on their life outside of CLL. So, keeping their symptoms to the absolute minimum, their physician keeping them informed about their disease progress, or lack thereof, in terms of keeping the disease at bay so they can focus on all of those things that bring them enjoyment outside of the CLL world. 

Katherine Banwell:

That’s great. Thank you for your perspective. One part of thriving  with CLL is managing the symptoms of the disease. What are the common symptoms of CLL? 

Dr. Jean Koff:

So, one thing that I see with nearly all of my CLL patients, regardless of where they are in the CLL journey, and regardless of whether they need active medications to manage their CLL, is some degree of fatigue. And this can range from just mild fatigue that patients notice that they need a little bit of a breather in the middle of the day, to needing more sleep at night, to not being able to exercise as much as they’re used to. And that is by far one of the most common symptoms we see. Again, whether or not their disease needs medication to manage it. The classic symptoms of CLL that often let us know that it’s time to start medical management, are not just this fatigue. But the classic symptoms are B symptoms. And we describe those as fevers, night sweats, and unintentional weight loss. Those are very common. And then some patients with CLL will also have what we call palpable lymphadenopathy, which is our term for lymph nodes that are enlarged that you can feel. And the most common places to feel these on the body are on the neck, under the arms, and in the groin.  

Katherine Banwell:

Okay. How are symptoms treated? 

Dr. Jean Koff:

So, if your symptoms progress to the point that your doctor thinks you need medication – they’re becoming disruptive to your life, or they are getting worse and worse over time, then there are a variety of medications that we can use in CLL. And this is actually a very exciting field. Right now, the state of the field is that most patients who are starting on their first treatment for CLL will use some sort of oral medication, and that may be accompanied by an IV – what we call monoclonal antibody, or it may not. But one thing that has really changed even since I very first started practicing, is that we no longer commonly use what I would call conventional chemotherapy to treat CLL. Even though this was the standard of care just a few years ago. 

Katherine Banwell:

Wow. So, a lot has changed. 

Dr. Jean Koff:

Yes, definitely. 

Katherine Banwell:

Why is it so important for patients with CLL to speak up and communicate with their healthcare team about some of their symptoms? 

Dr. Jean Koff:

Well, for starters we want you to feel better. That’s our number one job as – as physicians, is we want to get you to feeling to – to where you are feeling like your best self. CLL or not. So, we want to make you feel better. But in CLL your symptoms are actually one of the criteria we consider when we’re thinking about whether or not we need to start a new therapy, or if you’re somebody who’s already on therapy, whether we need to change your therapy. So, it’s actually very important and your CLL doctor should be checking in with you regularly to see if you have new or worsening symptoms that might be due to your CLL.  

Katherine Banwell:

Mm-hmm. It sounds like treatment of the disease is key to controlling your symptoms. So, let’s talk about treatment. Many patients are overwhelmed by the different types and classes of treatment. When is it time to treat CLL, and what are the options?  

Dr. Jean Koff:

So, I boil down the criteria to when you need to treat your CLL to two main categories. One category is that the disease is progressing quickly, and the other category is the disease is causing problems of some kind, or getting ready to cause problems of some kind. Those are some of the broad categories that we think about when it’s time to start treatment for CLL. Now, this – the groups that research CLL have put out various criteria that help guide physicians about when it’s time to start treatment and some of those more specific criteria include items like symptoms. So, symptoms are a very important part of that decision-making process.  

And the same symptoms that we mentioned, the B symptoms, fevers, chills, night sweats, weight loss that’s unintentional, or lymph nodes that you can feel, those would potentially be reasons that your doctor would want to start you on CLL therapy. But the CLL can cause issues even in a patient who’s not necessarily having symptoms. So, one of the most common ways that CLL can cause issues is the CLL cells can cause your other blood cells, the normal blood cells, to be low in number. There are several ways the CLL cells can do this. One of the most common ways is that the CLL cells which are often circulating through your bloodstream can also collect or overrun your bone marrow.   

And if you think about it, the bone marrow is the factory that makes all of your blood cells. So, when there are too many CLL cells in the bone marrow, they can crowd out the normal blood cells, like red blood cells or platelets. So, when red blood cells or platelets get low beneath certain thresholds, that’s a reason to start CLL therapy. 

Katherine Banwell:

Mm-hmm.   

Dr. Jean Koff:

So, there are a couple other criteria that we think about. CLL cells can collect in other areas, including the spleen. So – and if you remember, the spleen is a lymphoid organ that sits on the left side of your body that is right below the stomach. And so, if CLL cells collect in the spleen, they can cause it to be too big, it can press on the stomach, it can make it so you feel full, even if you haven’t eaten a full meal, that’s something we call early satiety. It can be uncomfortable, causing some abdominal pain. And if the spleen gets really, really big, it can cause it to not be able to do its normal job, which is to filter out the normal blood cells like it does every day. And so, that would be a reason to start therapy as well. And then the last – the last category I would think about is in CLL we have lots of – of CLL cells that are circulating in the blood that we can check with a routine blood count. And the absolute number of CLL cells is not as important as how fast that number is growing. So, your physician will track how fast that number of CLL cells is doubling.  

And if you meet criteria for what we call rapid doubling time, which is usually thought of as less than 12 months but certainly less than six months. So, if your count goes from 30,000 to 60,000 in under six months, then it may be time for you to start thinking about therapy. 

Katherine Banwell:

Right. So, Dr. Koff, would you briefly review the treatment classes? 

Dr. Jean Koff:

So, for first-line treatment, we have two main treatment classes that we think about at this time. The first is – is called BTK inhibitors which is Bruton tyrosine kinase inhibitors. And these are oral medications, so medications that you take by mouth, and the most well-studied of these is called ibrutinib, we typically prescribe ibrutinib by itself. There are other BTK inhibitors we are also now using in this space, one of them is called acalabrutinib and that is often given with an IV monoclonal antibody called Obinutuzumab.   

The other main class of drugs that we consider for first-line treatment of CLL is the BCL-2 Inhibitors. Right now there’s only one BCL-2 Inhibitor that’s approved for CLL and front-line and it’s called venetoclax. Usually, this drug is also given in the front-line with an anti-CD20 monoclonal antibody. So, the venetoclax itself is a pill you take. And the monoclonal antibody is an – either an IV or a subcutaneous injection.  

Katherine Banwell:

Where do clinical trials fit into CLL treatment? 

Dr. Jean Koff:

So, clinical trials are part of the reason, a big part of the reason that we’ve been able to make so much progress in how we treat CLL over the past few years. Clinical trials are how we figure out what treatments work for CLL, how patients feel on them, what sort of adverse events or side effects they have on individual treatments, and which treatments do better for keeping CLL symptoms under control, keeping the disease under control, and allowing patients to live longer and have a higher quality of life with their disease.  

Katherine Banwell:

Are there any other options available for CLL patients? 

Dr. Jean Koff:

So, there are other options. A clinical trial, if that is available to you as a patient is nearly always a good thing to consider if you have CLL. Because the vast majority of patients will not be cured by CL – by their treatment for CLL. Meaning that the – even though the treatments we have usually work for a very long time in most patients, ultimately the CLL will at some point, perhaps years down the road, progress and need another therapy. For that reason, we know we can do better. And we are hoping that the next clinical trial is going to lead to the discovery of a new agent or a new combinations – new combinations of agents that will allow patients to live longer with a better quality of life with CLL.   

Katherine Banwell:

Mm-hmm. 

Dr. Jean Koff:

So, that’s always a good option to consider. 

Katherine Banwell:

Mm-hmm. What are the common side effects of treatments, and how are they managed? 

Dr. Jean Koff:

So, each of the different classes of agents has a different profile of side effects. The BTK inhibitors, the first class that I mentioned with ibrutinib and acalabrutinib, are usually very well tolerated. The most common side effects that we tend to see are things that the patients can feel or see, but also things that we can see on the labs when we’re monitoring patients. So, sometimes you can see a lower platelet counts or lower cell counts with ibrutinib. That’s something that you may not notice, but your doctor’s going to notice on the – the blood counts when you come to the office. Sometimes ibrutinib can cause a rash or GI upset, this is usually easily managed with supportive care from your physician.  

And then some more – some more common effects of the BTK inhibitors include joint pain and headache. And again, many physicians, because we’ve been using BTK inhibitors for a long time, have a good regimen for treating these side effects. More uncommon side effects of BTK inhibitors, particularly ibrutinib that we look out for would be abnormal heart rhythms and some tendency for bleeding. But these are relatively uncommon and with newer BTK inhibitors, we’re seeing lower rates of these side effects.  

So, in terms of venetoclax side effects we have a little bit of a different profile. This agent is much more likely to cause lower cell counts, especially in a white blood cell count known as neutrophil count, and so your doctor will be monitoring you for that. In terms of patient side effects that you can feel, it can cause a rash, it can cause some GI upset. These are usually relatively easily managed but we want you as the patient if you’re on venetoclax to talk to your doctor about these side effects so that they can help you feel better and help you manage those. In terms of the anti-CV20 monoclonal antibodies, which we use a couple in CLL more frequently, they have very similar side effect profiles.   

So, one is rituximab, and one is obinutuzumab. Obinutuzumab is usually used in combination with venetoclax in front-line CLL.  

Like I mentioned before, this is an infusion and most of the side effects that we think about and most commonly see in these anti-CV20s are side effects that patients have during the infusion. And these are referred to as infusion reaction. And these are relatively common, around 30 percent in these anti-CV20 monoclonal antibodies. So, what is an infusion center react – er sorry, what does an infusion reaction look like? This looks sort of like an allergic reaction.  

Katherine Banwell:

Hm.  

Dr. Jean Koff:

So, your nurses in the infusion center are going to be monitoring you very carefully once you start the infusion, and they’re going to start it at a low dose, very slowly. But the side effects they’re monitoring for, they’re looking for changes in your heart rate or blood pressure. You may start to feel hot or cold or sweaty, you may have chills. Sometimes patients can have swelling in their throat or their tongue. And what will happen is because these are fairly common, is we’re still able to give the anti-CV20, but what we do is the nurse will stop the infusion, they may give you some medications that calm down that infusion reaction. So, medications 

 like antihistamines –  

Katherine Banwell:

Mm-hmm. 

Dr. Jean Koff:

Or steroids that help tamp down that immune response, and then they start the anti-CV20 infusion at a lower rate. The vast majority of patients will be able to receive an anti-CV20 antibody even if they have an infusion reaction. They may just need a little bit more of those immune-tamping down medications like antihistamines and steroids. And then the last thing to consider, which I think we’ve mentioned, especially in the venetoclax-containing regimens, is the Tumor lysis syndrome. And so, that is a side effect like we mentioned is kind of like the venetoclax working really, really, really well, of the tumor breaking down too quickly.  

And so, patients who have Tumor lysis, if they’re at high-risk, hopefully they’re already being monitored very closely with frequent lab draws, and they may receive medications that – that diminish the risk of adverse events happening because your electrolytes are out balance, for instance, your potassium is too high, or your calcium is too low. Because your doctors are monitoring you closely, they can give you medications that can help balance out those – those electrolytes and help protect the kidneys. The Tumor lysis is typically not a risk after the initial doses of venetoclax.  

So, the first couple weeks is when we typically monitor that, and then once the CLL has been broken down, or as I like to say, once it’s been cooled off a little bit, then you no longer have this risk of Tumor lysis and it – it doesn’t require further monitoring.  

Katherine Banwell:

That’s great information, thank you. What is the patient’s role in deciding on a treatment plan? 

Dr. Jean Koff:

So, it’s very important that the patient be involved in deciding on a treatment plan. Especially in first-line. Because we have these two excellent classes of agents, the BTK inhibitors and the venetoclax- containing regimens. Both of them have been shown to have very good what we call efficacy in CLL, meaning that they’re able to control the disease, patient’s symptoms largely at bay for long periods of time. You know, we’re talking an average of years that – that patients are on these therapies. And they each, like I said have different side effect profiles.  

And they’re given in slightly different ways. And so, right now we don’t have data from our clinical trials comparing a BTK inhibitor regimen to a venetoclax-containing regimen in CLL patients to tell us one is better than the other. And so, for that reason, a lot of the decision-making about which therapy is going to be better for you, or which therapy you would prefer, lies with the CLL patient rather than with the doctor. And the things that I ask my patients to consider, there are a couple different things. One is the side effect profile. So, patients may be more or less comfortable with certain side effects of one drug compared to another. Or there may be something in the patient’s medical history that puts them more at risk for a certain side effect than another. 

The other major player in this decision-making process is how these drugs are given. So, with ibrutinib, the ibrutinib is given as a pill that you take once a day, and you take it indefinitely. Meaning you take that pill once a day for as long as it’s doing what it’s supposed to do, which is keeping your CLL under control, and as long as the patient is tolerating it well. Meaning you’re not having a lot of uncomfortable side effects from the ibrutinib. So, I have patients who have been on ibrutinib for years and years and years and years.  

The venetoclax-containing regimen for patients who are getting their first-line treatment in CLL is different. It is designed as a – what we call time-limited therapy. And so, this regimen is given in – over about 12 months, 12 or 13 months, and then stopped. As long as the patient has had a good response. The other thing to consider with the venetoclax regimen, it’s not just the pill. You do take a pill every day, but you also get a – an infusion for about six months of the monoclonal antibody. Meaning that you’ll have to come into the infusion center and get an infu – an IV infusion of this drug called Obinutuzumab. The last consideration with the venetoclax regimen that differs in how it’s administered, is the venetoclax often works so well that it can break down the CLL cells a little bit too quickly.  

And so, for patients who have a very, very high white count, or large lymph nodes due to their CLL, there is a risk of something we call Tumor lysis syndrome, which refers to the process where the tumor cells break down very, very quickly, and they produce molecules that are released into the bloodstream that can be dangerous if they get too high or too low. And so, sometimes, in some patients we have to monitor for the Tumor lysis syndrome by checking labs fairly frequently after we start the venetoclax. And for some patients that means they have to stay overnight for a night or two in the hospital for lab monitoring.  

So, for some of my patients that I talk to about venetoclax, they say I want to stay out of the hospital, I just want to take a pill, I’m fine taking a pill, I’ll go with the BTK inhibitors. For other patients, they say I don’t want to be on a pill every single day, I will go through this year of therapy, I’m comfortable with that, and I’m happy that I’ll be able to take a break from therapy after one year. So, that ends up being a large factor in many of the conversations I have with my patients about which therapeutic approach we’re going to use in front-line therapy. 

Katherine Banwell:

Hm. Dr. Koff, we received a patient question prior to the program. If I’ve had FCR for my first treatment, does that prevent me from having – or having to take an oral drug later on? 

Dr. Jean Koff:

Absolutely not. So, the very first clinical trials that we did studying these regiments, especially the BTK inhibitors, were performed in patients who had received conventional chemotherapy like FCR. And what we saw is that patients who had received conventional chemotherapies and had – and needed retreatment of their CLL responded very, very well to agents like ibrutinib. And ibrutinib was able to control their disease, control their CLL, without them needing additional therapy for a long time. And that was actually the original indication for ibrutinib, was patients who had what we call relapsed CLL, often after these conventional therapies.   

Katherine Banwell:

Hm. Let’s turn to medication management. Excuse me. With oral medications available to treat CLL, patients now have the role of self-administering with their treatment program. How does this work exactly? 

Dr. Jean Koff:

So, just as you would receive a prescription from one of your doctors to manage your high blood pressure with a bottle of pills, you would also receive a special prescription from the doctor who is managing your CLL, a prescription for one of these oral agents. Either the BTK inhibitors or a venetoclax. And you would be – you would have the instructions on the pill bottle, just as you would you know another prescription and you would take the medication by mouth, every day, as instructed. 

Katherine Banwell:

Okay. What happens if a patient forgets to take their medication? Does it impact efficacy? 

Dr. Jean Koff:

So, forgetting a dose for one day, or having to skip a dose for another reason, or even a few days, shouldn’t have a major impact on controlling the CLL. And that’s true for two reasons. One, you’re going to start taking your medication again, you know fairly soon after you miss that dose. The next day. Or – or in a few days. But also, the – what we call the half-lives of these drugs are relatively long, and so you have some activity of the drug in your system in its ability to control the CLL, even though you haven’t taken the dose that you missed that day. In fact, sometimes we have to hold CLL medications.   

Maybe you’re getting a procedure, some sort of surgical procedure, and you might be at an increased risk of bleeding just in the day or two before and after that surgical procedure, so we would actually recommend that you hold a BTK inhibitor, if that was what you were receiving for your CLL, and then resume it once your risk of bleed had gone down a few days after the surgery.  

Katherine Banwell:

Hm. 

Dr. Jean Koff:

We do recommend that if you are going to miss a dose of your medication that you let your clinical team know, just so they can instruct you on how to resume your dose if you haven’t already gotten instructions from them about that. 

Katherine Banwell:

Okay. That’s really helpful information. What strategies are there to keep on schedule and remember to take the medication on time and regularly?  

Dr. Jean Koff:

So, I think these strategies are good whether you have CLL or some other type of disorder that you’re taking medication for. My patients often use labeled pill boxes with days of the week and a.m. and p.m., so that you know whether you took your pill that day and what time of day you took it. And so, setting that out for the week can be very helpful in organizing and making sure that you can check back and remind yourself whether or not you took your pill. 

Katherine Banwell:

How are patients monitored during treatment? 

Dr. Jean Koff:

So, your doctor is going to monitor you more closely when you first start a medication. So, I typically monitor my patients within one or two weeks of them starting an oral drug. One to make sure that they’re feeling okay on it, that they’re not having any side effects when they first start, but also to check lab values and make sure that the – the oral medication isn’t causing any problems with their blood counts or with other labs. Then, once we’ve established that they’re doing well on the medication, maybe they’ve come in every couple weeks for a month or six weeks, we start to space out those visits.  

I usually see my patients who are on active therapy about every three to six months to check and see whether they’re feeling okay, whether they’re having any side effects from the medicines, like I said to check their labs, make sure the medications aren’t causing any lab abnormalities. And also in the longer term, to make sure that their CLL is under good control on – on the medications. Because that’s one of our main goals is to keep the CLL under good control.  

Katherine Banwell:

We received another patient question prior to the program. Has there been any progress in helping CLL patients get a better reaction from COVID vaccines? 

Dr. Jean Koff:

That is a great question, and that is one that is near and dear to my heart and my colleagues at – at Emory. You raise a really good point, which is that CLL patients have altered immune systems just by virtue of their CLL. The CLL cells exert their influence on other immune cells and can cause your immune system not to respond to infections or immunizations the way it normally would. That’s without any medication in the mix. Now, when we look at patients who are on medications like the ones we’ve been talking about, the BTK inhibitors, venetoclax, but especially the monoclonal antibodies that react against CD20, we see that those patients really do not have an optimal response to vaccines, especially the COVID vaccine. 

Meaning, that patients who receive the COVID vaccine while they’re on that therapy, or even within twelve months of receiving a monoclonal antibody, often don’t mount the same strong immune response as somebody who’s not on those therapies. So, luckily, we – we don’t have to just depend on the vaccines. I still recommend that my patients get vaccinated, because it is safe and it might impart a little bit of efficacy, and it’s certainly more effective than not getting the vaccine. But we also have other approaches to increasing your protection against COVID, including the – the injection called Evusheld, which can help protect patients specifically whose immune systems are not completely normal and are not expected to mount a strong response to COVID vaccines.  

So, that is definitely a discussion to have with your doctor about how your medications impact your protection from COVID, from vaccines, and whether there are other medications that might be used to help increase your protection.  

Katherine Banwell:

That’s great advice. Dr. Koff I’d like to get your thoughts on where we stand with progress with helping people live longer and truly thrive with CLL. What would you like to leave the audience with? 

Dr. Jean Koff:

So, I think that one thing to remember with CLL is over the past few years we’ve seen an explosion in how we manage the disease because we have newer agents and therapeutic combinations that are helping people control their CLL for much longer than was possible 10 or 15 years ago. We still have a long way to go because ideally, we want every patient to be able to control their CLL and thrive with CLL for as long as possible. And, right now like I said before, we are not curing patients yet. Meaning that we don’t have a therapy that can get rid of the CLL, make it go away, and keep it away forever.  

That’s where clinical trials come in. That’s where we are able to make progress, is we’re able to study what therapies work, what therapies don’t, how they perform against each other, how they make patients feel, and what sort of side effects might be associated with them. And so, that’s really the next step, is continuing the work that has already been done in clinical trials and exploring these new therapeutical approaches. 

Katherine Banwell:

Dr. Koff, thank you so much for taking the time to join us today.   

Dr. Jean Koff:

Thank you for having me. 

Katherine Banwell:

And thank you to all of our collaborators. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs. To learn more about CLL and to access tools to help you become a more proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks so much for being with us today. 

Clinical Trials As a CLL Treatment Option: What You Should Know

Clinical Trials As a CLL Treatment Option: What You Should Know from Patient Empowerment Network on Vimeo.

 Should you consider participating in a CLL clinical trial? In this webinar, Dr. Adam Kittai provides an overview of the clinical trial process and addresses common misconceptions. Dr. Kittai shares an update on the latest advances in CLL research and discusses key advice for patients considering 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.

Download Guide

See More from CLL Clinical Trials 201

Related Resources:

What Helps Determine a CLL Patient’s Treatment Options

Setting CLL Treatment Goals WITH Your Team

Expert Advice for CLL Self-Advocacy

Transcript:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss the latest research advances in chronic lymphocytic leukemia and discuss the role of clinical trials in patient care. Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access information to follow along during the webinar. At the end of this program, you’ll receive a link a link to a program survey. This will allow you to provide feedback about your experience today and it will help us plan future webinars.  

Finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your health care team about what might be best for you. Okay, let’s meet our guest today. Joining me is Dr. Adam Kittai. Doctor, welcome. Would you please introduce yourself?  

Dr. Kittai:

Thanks for having me. My name is Dr. Kittai, I’m an Assistant Professor at the Ohio State University, and I specialize in research and clinical research in Chronic Lymphocytic Leukemia.   

Katherine:

Great. Thank you so much for taking the time to join us today.  

Dr. Kittai:

Happy to be here.  

Katherine:

I understand that CLL researchers met recently at the annual American Society of Clinical Oncology meeting, also known as ASCO, to share their research. Are there highlights from the meeting that patients should know about?  

Dr. Kittai:

Yeah, so this time of year, there are two main conferences actually that are very important to the CLL groups at large, as well as the oncology community. So, there’s ASCO and then there’s EHA, the European Hematology Association. And in general, there was a lot of exciting things at both of these conferences. 

In CLL, we have two main treatments that we’re really focused on. One is called the BTK inhibitors, which is ibrutinib, acalabrutinib, and zanubrutinib that you may have heard about. And the other treatment regimen is called venetoclax, and that’s usually paired with something called obinutuzumab. So, right now we’re either using the BTK inhibitors or the venetoclax as our frontline therapies. And typically, when patients progress on either one of those treatments – their disease gets worse – we switch to the other one. 

And so, what I’m getting to be that right now, that paradigm of starting with one therapy – the BTK inhibitors or the venetoclax – and then switching to the other, or vice versa, is being challenged. How that’s being challenged is combining the two medications together to see if combining them together is better than giving them sequentially. So, I think this is the primary research that’s being looked at in the world of CLL and we got some updates to show that the combination of the BTK inhibitors, plus the venetoclax, is looking quite good. It’s looking like it’s inducing deep remissions in some of our patients.  

Some of the challenges here though that we still need to figure out is that a lot of these combinations are leading to more toxicity. So, ultimately, I think we’re going to have a discussion about who is the appropriate patient for the combination, as opposed to giving it sequentially. 

There’s also a lot more research going on, looking at what we call randomized trials, which we’ll get to in a second, to determine if the combination is better than giving it sequentially. Right now, we just have what we call single-arm studies that kind of show safety and how well the trial works. But really, the definitive clinical trials – and once again, we’ll get to this a little bit later – are going to be randomized study where we randomize patients to the combination versus the sequential therapy to determine if doing it together is better than doing it sequentially.  

So, I would say that this new treatment paradigm of combining our two main treatments up front is looking quite good. We’re worried about some of the toxicities when we combine these medications, and we’re still not quite sure if combining them is the right approach, if it actually is superior to giving them sequentially. So, I think that’s the name in research right now for CLL, whether or not combination therapy is better than sequential therapy. The jury is still out, but some of the new data we saw was exciting. 

Katherine:

So, how can patients stay up to date on research like this as it develops? 

Dr. Kittai:

Yeah, great question. So, for one, you can talk to your physician. A lot of the physicians will go to either ASCO or the European Hematology Association and be able to come back with some of this data to share with their patients. And then also, there’s a lot of smaller conferences that local oncologists will go to get highlights from these particular conferences, where they also will come back to the patient to let them know some of this highlighted research. I think that’s probably the easiest way for patients to get access to this research. And Google’s our friend, right? And so, a lot of things are available on Google if you know where to look for them. 

Katherine:

Right. So, a key part in moving forward with CLL research is clinical trials, right? So, for people who may not know the term, what is a clinical trial? 

Dr. Kittai:

Yeah. So, a clinical trial is an experiment where patients are enrolled to receive a treatment that is either new or new in a new setting – so, an old treatment in a new setting – and we’re looking to see whether or not the treatment leads to improved outcomes for our patients.  

Katherine:

Why would a CLL patient consider participating in a trial? What’s the benefit for them? 

Dr. Kittai:

Yeah, great question again. The benefit of a clinical trial is two-fold. One is that by participating in a clinical trial, we are collecting data to determine what’s best for patients moving forward. [00:07:06] So, in a way, by participating in a trial, you’re contributing to the benefit of CLL patients in the future to help us determine what’s best for everybody moving forward. That’s one reason to go on a clinical trial. Another reason to go onto clinical trials is that it allows for access to therapies that may not be available otherwise, which may work better than what we already have and may be safer.  

Katherine:

Right. So, I’d like to walk through a few common questions that patients have about clinical trials. And here’s a concern we received from a patient prior to the webinar. “I’m nervous that I will receive a placebo if I join a clinical trial.” So, first of all, would you define a placebo?  

Dr. Kittai:

Sure. A placebo is usually a sugar pill or something that has no effect. That’s what a placebo is.  

Katherine:

And is it true then, would a patient possibly get a placebo in a CLL clinical trial? 

Dr. Kittai:

Not typically. So, in terms of clinical trials for CLL, we have a lot of treatments that are effective and safe in CLL. And so, we don’t typically design trials where you’re not getting some kind of active therapy. It would be extremely rare, and I don’t know of any trials currently that involve patients getting a placebo for CLL. Because it wouldn’t be ethical for us to enroll a patient on a trial where they would get a placebo instead of active therapy. 

Katherine:

Right. That makes sense. Here’s another question from an audience member, and I think this is probably a common concern for patients. “Is a clinical trial only something I should consider if there are no other options?” 

Dr. Kittai:

So, in my opinion, you should always consider a clinical trial, even if there are other options. And it’s because of those two reasons that I mentioned earlier. Number one, it benefits the CLL community as a whole to participate in the trial so that way doctors and researchers can collect data to improve outcomes for patients with CLL. And also, even though our drugs currently work really well, we don’t know how well they’ll last for, right? So, they still don’t know for certain how long our current drugs are going to work for in the future.  

And we’re always trying to do better. We’re always trying to create some sort of treatment, some sort of treatment paradigm that might be safer, as well as work better, and either of those goals is approvable. All of our drugs come with toxicity, right? And even though they’re really safe and they work really well, we’re hoping to develop something that is even safer and works even better.  

Katherine:

Yeah. It sounds, then, like trials can be considered throughout a patient’s life with CLL. What concerns do you hear from your patients?  

Dr. Kittai:

Yeah, so I think the primary concern I hear about a trial and the difference between going on a trial and standard of care, is that typically for a trial, it does require a little bit more from the patient. Meaning that there’s usually more visits – whether it is to monitor the effect of the new medication or new medication combination on the patient, whether or not it’s affecting their laboratory values or how they’re feeling.  

Or there might be parts of the trial that require invasive procedures. So, for instance, many trials will require bone marrow biopsies where a standard of care won’t. And the reason why the collection of those bone marrow biopsies is important for the trial is to better get an idea of how the treatment is working on a patient’s body.  

So, I think those are the two primary concerns I hear from the patient. Number one, it typically is a bigger time commitment with more visits to the doctor because we have to closely monitor the patients while they’re on trial. And number two is sometimes the trial involves procedures that otherwise wouldn’t be indicated for standard of care.  

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.  

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.  

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.  

Katherine:

Okay. 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.  

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, excuse me. 

Katherine:

That’s really good information to have.  

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.  

Katherine:

Yeah. I’m glad you brought that up. As we wrap up the program, Dr. Kittai, I’d like to get your final thoughts. What message do you want to leave the audience with related to clinical trial participation?  

Dr. Kittai:

Yeah. So, I would say that in the last ten years, there’s been a revolution in the way we treat CLL, and we wouldn’t have gotten here without clinical trials. So, the reason why we have the BTK inhibitors – the ibrutinib, acalabrutinib, and zanubrutinib – and the reason why we have the BCL-2 Inhibitor venetoclax, and the reason why these have changed the way that we treat CLL making our patients live longer with better safety profiles is because of clinical trials. And so, I am a firm believer that if we can enroll a patient onto a clinical trial that’s appropriate, who might benefit from the trial, then they should enroll in the clinical trial if possible.  

So, I strongly encourage everybody to enroll onto clinical trials, to get access to, you know, groundbreaking new therapies. And once again, I want to highlight that the point of a clinical trial is to improve safety or to improve efficacy and that’s why we develop clinical trials and that’s the hope by running it.  

Katherine:

Okay, that’s great advice. Dr. Kittai, thank you so much for joining us today. It’s been a pleasure.  

Dr. Kittai:

Yeah, it’s been a pleasure to you. Happy to be here. 

Katherine:

Thank you.  

And thank you to all of our partners. If you would like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this webinar. It will help us as we plan programs in the future.  

To learn more about CLL and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today. 

Signs It Is Time to Treat Your CLL

Signs It Is Time to Treat Your CLL from Patient Empowerment Network on Vimeo.

When is it time to treat your chronic lymphocytic leukemia (CLL)? Dr. Catherine Coombs reviews the criteria doctors consider when deciding whether it is time to begin therapy. 

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

See More from Thrive CLL

Related Resources:

What Helps Determine a CLL Patient’s Treatment Options?

Expert Advice for CLL Self-Advocacy

Refractory vs Relapsed CLL: What’s the Difference?

Transcript:

Katherine:

When is it time to treat? What factors do you look at? 

Dr. Coombs:

There’s pretty well-established guidelines for when treatment is indicated. The international workshop for CLL has these published guidelines, so it’s something you could Google. Off the top of my head, the main reasons that I do treatment, which are included in these guidelines, are one, if the patient has low blood counts due to the CLL, so that could be anemia or low platelets. Two, if they have bulky lymph nodes. They actually define bulky as 10 centimeters. So, that’s pretty big.  

Or, if the lymph nodes are being symptomatic in some way, they’re bothering the patient, they don’t have to be that big. Three, if the patient has bulky spleen enlargement or if it’s causing symptoms. The spleen is next to the stomach. So, say some patients may not be able to eat a full meal, that’s another reason we could do treatment.   

Another reason is if the CLL is causing constitutional symptoms. Sometimes these are black and white. One is unintentional weight loss of 10 percent or more of the body weight. The one that’s not always black and white is fatigue. Patients can have fatigue from the CLL, but I’ve found often fatigue can be due to other causes. So, that’s something I consider an important job of mine is to make sure we don’t jump into CLL treatment if say, there’s some other cause for the tiredness, such as, say the thyroid’s off, or there’s a huge amount of stress due to some other factor outside of the CLL.  

Then, some other constitutional symptoms are CLL can cause fever or drenching night sweats. Those two it’s important to make sure that there’s not a concurrent infection because infections can also cause those symptoms. The last indication is patients with CLL can develop autoimmune cytopenias. That’s when the immune system attacks some component of the blood cells. Most commonly that’s an autoimmune anemia or autoimmune thrombocytopenia. That’s the term for low platelets.  

Usually, we can treat that with steroids or occasionally CD-20 by itself like rituximab to calm down the immune system. However, if those immune-based therapies fail the patient, then we could consider treating the CLL to help fix that problem.  

Thriving With CLL: What You Should Know About Care and Treatment

Thriving With CLL: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

What does it mean to thrive with chronic lymphocytic leukemia (CLL)? CLL expert Dr. Catherine Coombs discusses the goals of CLL care, reviews current treatment options, and shares tools for taking an active role in decisions.

Dr. Catherine Coombs is an Assistant Professor of Medicine in the Division of Hematology at The UNC Lineberger Comprehensive Cancer Center. Learn more about Dr. Coombs here.

See More from Thrive CLL

Download Program Guide


Related Resources:

Thriving with CLL Resource Guide

What Are the Goals of CLL Treatment

What Are the Goals of CLL Treatment?

An Overview of CLL Treatment Types

Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re focusing on how to live and thrive with CLL. We’re going to discuss CLL treatment goals, and how you can plan an active role in your care.  

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Catherine Coombs. Dr. Coombs, welcome! Would you please introduce yourself? 

Dr. Coombs:

My name is Catherine Coombs. I am an assistant professor of medicine at the University of North Carolina. My main patient practice is CLL and SLL patients, which make up probably about 80 percent of the patients I see. I do see a couple other types of leukemia and precursor states as well.  

Katherine:

Thank you so much for taking the time out of your schedule to join us today; we appreciate it.  

Dr. Coombs:

No problem. My pleasure.  

Katherine:

Since this webinar is part of PEN’s Thrive series, I thought we could start with getting your opinion on what you think it means to thrive with CLL? 

Dr. Coombs:

I’d say the first thing that comes to mind when I hear thriving in CLL is my goal for all my patients, which is to live their lives and enjoy their lives, and to not let CLL take over their lives in any way. But it’s of course important to be knowledgeable and educated about how the disease can impact one’s life. But I think there is a lot of education that can also go with that to help individuals continue to enjoy their lives and do most of the activities they like within reason.  

Katherine:

This helps us guide us through the conversation, so thank you for that. Appropriate treatment obviously is part of thriving. Before we get into the specifics of CLL treatment approaches, how would you define treatment goals?  

Dr. Coombs:

The first thing to jump into prior to going into treatment goals is asking the question, “Is treatment even needed?” CLL, in contrast to pretty much most other cancers, is not one of the cancers that needs to be treated immediately.  

At least in 2022, there’s no proven benefit to early treatment. That is being questioned now that we have drugs that are much better tolerated. There are some nice clinical trials asking that question again, “Is early treatment beneficial?” At least what we know now is that is not the case. As it turns out, probably up to a third of patients with CLL never need treatment in their lifetime. That means that the disease progresses along usually at a slow pace, and individuals die from something else: any number of other potential causes of death.  

The other two-thirds plus do need treatment at some point in their lifetime. The goals of treatment kind of depend on the patient. There’s not a one-size-fits-all approach in my view. I think it depends on what is most important to the patient.  

I’ll give two drastic examples just to show how goals can be different. CLL often is a disease of older individuals. The average age of diagnosis is usually around 70 or so. But many patients have the disease for a few years, if not longer, prior to needing therapy. So, one example patient could be an 85-year-old individual who has had the disease for a decade and finally needs treatment. The goals of that patient may be to control disease, but he or she may not be worried about going into a deep remission, and may be very, totally willing to be on a drug. And definitely in order to control the disease, alleviate disease-related symptoms, but perhaps not get into a deep remission.  

The other patient, just to take it to another far extreme, I work in an academic medical center; I see some very young patients which is not the norm in CLL, but it does happen.  

Say it’s a 40-year-old patient. His or her goals may be very different. They may not like the idea of being on an oral therapy indefinitely or until progression. So, the goals for that patient may be different. They may say, “Gosh, I’d like to do something a bit more intense to be able to be off of therapy.”  

So, I think in the end there’s no one-size-fits-all approach. It generally, for my clinic, comes down to a discussion with the patient talking about what their goals are: is it more important to be off therapy for some period of time and they’re willing to sacrifice a bit more intensive of a schedule? Or are they more appealing to be on a regimen that they’re on indefinitely provided that it still provides disease control and alleviation of the disease-related symptoms.  

Katherine:

That leads me to my next question, which is what is the patient’s role in setting care goals? 

Dr. Coombs:

I think they should have a huge role; it should be a shared decision between the patient and their cancer doctor. I think at least as of now, there’s not one proven best therapy. We have a number of therapies that work extremely well. But they differ quite a bit with respect to the schedule, the possible side effects profile, and sometimes in the cost, depending upon the patient’s insurance. 

Knowing that there’s not a superior therapy, I think the best approach would be to discuss all of the therapies that are highly effective, and then compare and contrast what those therapies may look like for the patient and then make a shared decision.  

Katherine:

I have a follow-up question to what we were talking about a moment ago. What would you say to a patient who has a lot of anxiety about having to wait for treatment? 

Dr. Coombs:

The first thing I would say is that anxiety is normal. More often patients are anxious than not because it’s really hard to be told you have a leukemia and that we’re not going to do anything about it. I think that’s really hard to hear. The way that I try to counsel people is that my role as the doctor is to do no harm. If you have a leukemia and there’s no proven way to make you live longer by giving therapy early on, if you’re in that early stage of CLL where you’re asymptomatic, by offering therapy, all I could do is make you worse.  

I could give you a new side effect, I could add a new cost burden – Until I have data to prove that that’s going to make your life longer, which we do not have yet (maybe that will be different five to 10 years from now, but we do not have that yet), I could only hurt you. So, that’s not what I want to do. I want to have you live and thrive.  

The better thing to do, based on what we know now and what we know our therapies can and can’t do is to do the watchful waiting. But the anxiety is normal. Depending on how severe the anxiety is, I have had patients meet with – at least at UNC we have something called the Cancer Center Support Program, which is a group of psychiatrists, psychologists, therapists that can help talk over what it means to have a cancer diagnosis and not necessarily need therapy.  

Then I also provide education on the other health issues that can come up as part of being a CLL patient even on that watchful waiting program. The thing that we talk about the most is the increased risk for infections, which in the era of the COVID pandemic is a major concern. Luckily, we have a lot of ways to decrease the health risk for COVID, whether it’s due to the administration of vaccines, or monoclonal antibodies, which I think we’ll talk about more later.  

There’re a lot of ways that people can live with it. I do think the anxiety is normal. At least in my own practice, I’ve found that most of the time the anxiety lessens with time. Because it becomes a part of who you are. It doesn’t have to be all of who you are: people can live their lives largely the way they did before with a bit of extra knowledge about things that can come up in the future but may never come up at all.  

Katherine:

Let’s walk through the types of treatments that are used today to treat CLL.  

Dr. Coombs:

So, for the non-watch and wait category, that means we are now thinking about therapy. Most of the time that involves a targeted agent.  

We largely are using a lot less in the way of cytotoxic chemotherapy. Not to say there isn’t a role for it, but in my own practice, it’s not something that I have been using in the past several years because it’s highly toxic. It is effective, but it can lead to some long-term toxicities. And it’s also not quite as effective as these new targeted agents. So, those fall into two major classes.  

The first class is a class of drugs called BTK inhibitors. That stands for brutons tyrosine kinase. That’s an important target in the CLL cells, specifically. The CLL cells are a type of B-cell. So, BTK is important for the signaling of both normal and cancerous B-cells. When we use drugs to block that protein, that impairs the CLL cells’ ability to multiply. Then we ultimately are able to control the disease with prolonged administration of one of these drugs.  

There are two FDA-approved BTK inhibitors. The first FDA-approved agent is a drug called ibrutinib. And then the newer agent is called acalabrutinib. There’s another drug that you may have heard of called zanubrutinib. That is not technically yet FDA-approved for CLL, but it is occasionally used given that it is FDA-approved for other lymphomas, and it is within the national cancer center network guidelines for CLL treatment.  

The big benefit of these drugs is they work phenomenally well at controlling the CLL. I would say the major downside is that they do have to be taken indefinitely. So, patients ask, “Am I going to be on it forever?” Well, it depends on what you mean by forever. We generally keep patients on these drugs as long as No. 1 they’re tolerating them, so no bad side effects, and then No. 2 as long as the CLL is staying under control.  

So, for that 85-year-old patient that I gave as an example, forever may be until the rest of their life. Because they can work for six, seven, eight plus years; so, they’re highly effective. Some patients may go on them and then die from something else years down the road. For the younger patients, or patients who progress faster, we would then put them on something else whenever the drug stopped working, provided that they didn’t have a significant side effect to the drug class. So, that’s a big first class.   

The second large subset of therapies is a drug called venetoclax, which we typically combine with an anti-CD20 drug. The one that we use for patients who are getting their first treatment is called obinutuzumab. Venetoclax is a BCL-2 Inhibitor that inhibits this pathway within CLL cells. It’s not unique to CLL cells, but the CLL cells are particularly dependent upon it called apoptosis.  

So, when they get exposed to this drug, the CLL cells just die; they can’t continue living, they die off. So, venetoclax works really exquisitely well at killing off CLL cells. Probably works better when it’s paired with this drug obinutuzumab. That’s how it was approved in the frontline setting: those two drugs together. The big risk of that therapy, essentially, it’s kind of a weird risk, when the CLL cells die too quickly that can cause some problems in the human body because one has to metabolize all the debris left over from these dead cancer cells. The medical term we use for that is Tumor Lysis Syndrome. 

That can actually be fatal if not done in a safe way. Fortunately, when we do it as per the recommendations by the manufacturer, we’ve not had any adverse severe problems from it. It ends up being that the patient has to come in weekly every five weeks to do a slow ramp-up of the drug to kind of slowly kill off the cancer cells so that the body isn’t overwhelmed by the contents of these dead cancer cells.  

The big advantage of this regimen is that because it kills the CLL so well, people can get into very deep remissions. So, instead of being a therapy that people are on indefinitely, it’s designed as a one-year therapy when given as the first therapy. So, it’s one year and then they’re done. People after that are in remission, they’re not on any treatment. They may feel like they don’t have CLL.  

Most of the time the CLL does come back. It depends on does the patient come back for something else? Which does happen when people are older. But it appears that it keeps people in remission for several years. The median, which is how long it takes for half of patients to have their disease come back, the median progression for survival has not yet been reached for the trial that was done using this therapy.  

So, that’s at least three, four plus years that we’ve been able to follow people. So, very attractive in that you’re done and then you just wait for the disease to come back but largely feel good in the interim.  

Katherine:

When is it time to treat? What factors do you look at? 

Dr. Coombs:

There’s pretty well-established guidelines for when treatment is indicated. The international workshop for CLL has these published guidelines, so it’s something you could google. Off the top of my head, the main reasons that I do treatment, which are included in these guidelines, are 1.) If the patient has low blood counts due to the CLL, so that could be anemia or low platelets. 2.) If they have bulky lymph nodes. They actually define bulky as 10 cm. So, that’s pretty big.  

Or, if the lymph nodes are being symptomatic in some way, they’re bothering the patient, they don’t have to be that big. 3.) If the patient has bulky spleen enlargement or if it’s causing symptoms. The spleen is next to the stomach. So, say some patients may not be able to eat a full meal, that’s another reason we could do treatment.  

Another reason is if the CLL is causing constitutional symptoms. Sometimes these are black and white. One is unintentional weight loss of 10 percent or more of the body weight. The one that’s not always black and white is fatigue. Patients can have fatigue from the CLL, but I’ve found often fatigue can be due to other causes. So, that’s something I consider an important job of mine is to make sure we don’t jump into CLL treatment if say, there’s some other cause for the tiredness, such as, say the thyroid’s off or there’s a huge amount of stress due to some other factor outside of the CLL.  

Then, some other constitutional symptoms are CLL can cause fever or drenching night sweats. Those two it’s important to make sure that there’s not a concurrent infection because infections can also cause those symptoms. The last indication is patients with CLL can develop autoimmune cytopenias. That’s when the immune system attacks some component of the blood cells. Most commonly that’s an autoimmune anemia or autoimmune thrombocytopenia. That’s the term for low platelets.  

Usually, we can treat that with steroids or occasionally CD-20 by itself like rituximab to calm down the immune system. However, if those immune-based therapies fail the patient, then we could consider treating the CLL to help fix that problem.  

Katherine:

We received an audience question prior to the program. They asked, “What does it mean to be refractory, and how is that different from relapsing?” 

Dr. Coombs:

I actually just had a conversation about this. I’m not sure that’s formally defined. I have heard one definition suggested is – I think everyone agrees refractory means you did not respond to your last therapy. That’s actually really bad. Most of our therapies work in almost everyone. So, refractory is a term that is generally accepted means no response. So, whatever therapy you’re on, the CLL did not get better, it got worse. That’s refractory.  

Another definition that I’ve heard based on this recent discussion is if you had a short remission duration, such as six months or shorter. Most of the therapies we use should work for quite a while, usually on the order of years. So, some people also consider refractory a short remission duration, six months or shorter.  

Relapse is probably the more common scenario. That’s a patient who has had some type of therapy, but they had a decent response, but that response wore off, more on a normal pace. Again, not on the order of months, but usually on the order of years.   

Katherine:

There’s not necessarily a one-size-fits-all approach to treating CLL, so how do you decide which treatment is right for a patient?  

Dr. Coombs:

I always look at their underlying disease biology. There’s a couple really important tests that I send for all of my CLL patients by the time that they need therapy. The first is to see what their underlying cytogenetics and molecular findings are. There are certain good findings, and then certain bad findings.  

One of the bad findings is having a deletion in the 17th chromosome in the short arm of that chromosome. The chromosomes are the big pieces of DNA within everyone’s cells. There are findings that are common in CLL: a 17p deletion is a poor prognostic feature. There’s a separate test where we can actually identify mutations in a gene called TP53. And these behave largely the same as 17p deletions, so I always check for both. It’s two different tests.  

Often times patients have both of these findings: a 17p deletion and a TP53 mutation. But sometimes you can have the mutation without the deletion and vise versa. That is one finding that’s important when talking about different therapies. The other really important prognostic test is the IGHV gene mutation status. This is another specialized sequencing test. It looks to see if the patient’s heavy chain, if their immunoglobulin protein has undergone something called somatic hypermutation or not.  

It’s actually good to be mutated. What we know about people who are mutated is that they typically have better responses to most therapies and their disease typically is one that grows slower. So, I use those factors and then I have a conversation with the patient. The two main treatment classes that I spoke about – so the BTK Inhibitors, those work actually really well and even the people with these bad prognostic features. So, people with the 17p deletion, people with the TP53 mutation, they can have disease control for six plus years on a BTK inhibitor, which is really good.   

That was not the case a decade ago when we didn’t have these drugs. That’s something that’s been hugely beneficial for our patients. The venetoclax/obinutuzumab regimen, that still works when people have the 17p or the TP53, but it probably doesn’t work as well.  

I’d mentioned the median time for disease to come back hadn’t been reached yet. It had been reached for that poor risk subset. The expectation for people with that poorest marker is that the median PFS, progression-free survival. So, again, when after someone starts therapy, when the disease then progresses is 49 months. It kind of gives me a rough estimate of, “Gosh, these are your therapy options and based on your underlying biologic factors unique to your disease, this is what you can expect out of therapy A or therapy B.”  

The mutated or unmutated IGHV, similarly, those BTK inhibitors work extremely well, even in people with the bad unmutated finding. I think those are always an option. The other treatment is an option, but the people with that bad finding do have a shorter time until they progress of just under five years.  

Katherine:

Dr. Coombs, why should patients feel confident in speaking up and being a partner in their care? Do you have any advice for helping them find their voice? 

Dr. Coombs:

Great question. I think a patient is their own best advocate. We as their physicians always try to advocate for them, but we often don’t know what their wishes and desires are. I think through speaking to what’s important to you, that can help me know a little more about what path we should take. There’s not always one right path.  

I’ve talked about these two great treatment options we have. I had one patient who loved fishing and he just didn’t want to be in the infusion center. That’s the person that should go on the oral drug, where he doesn’t have to come to and from as often. 

If you tell us about your goals and your desires, that helps us also be your top advocate because then we have a little more background for what’s important to you. I think that’s my main thought. We’re here for you, but we need to know what you value the most. We don’t always know that.  

Katherine:

When should a patient consider a second opinion or a consultation with a specialist? 

Dr. Coombs:

I never discourage a second option. I’m a CLL specialist, but I’ve had patients ask for a second opinion. I’m always enthusiastic about it. If a patient feels that they need another set of eyes on their case. I’ve learned some things from some of my patients who have seen specialists in different areas of the country or locally. We have Duke down the street. Sometimes different providers just have different perspectives.  

Or, sometimes the patient just needs to hear something again if it doesn’t sound right to them. I’ve had patients for example who are one watchful waiting who really just had trouble believing. “I have leukemia, and you’re really telling me to do nothing.” But then they hear it from someone else and it just helps it sink in. I’d say the answer is anytime. Anytime you think you need another set of eyes on the case.  

But I would say especially for people in the community. I do think there’s a lot of value in seeing a CLL specialist once if it’s something that you’re interested in and your insurance pays. I think the community docs have one of the hardest jobs, and I don’t think I could do it. There are so many different cancers that they have to know about. I think, if anything, I have the easy job; I have one tiny slice of the pie that I know a ton about. Not to say they don’t do great jobs; I’m actually phenomenally impressed with most of the community.  

However, they have so much to know, often you can maybe get a little more of a unique view on CLL by seeing a CLL expert. If that’s in your interest. But certainly not mandatory, especially if your goal is to stay away from doctors.  

Katherine:

COVID is of course another factor that impacts a patient’s ability to fully thrive with CLL in today’s world. Many CLL patients are concerned about the effectiveness of the COVID vaccines and their ability to make enough antibodies to fight the virus. So, what do we know about how effective the COVID vaccines are for people with CLL? 

Dr. Coombs:

The COVID vaccines – we were fortunate in being able to build on some earlier research. Even prior to being able to look at the data for COVID vaccines, there have been studies looking at vaccines in general in CLL. That’s actually been a long-term established issue, which is that based on earlier studies we knew most vaccines were not as efficacious in individuals with CLL compared to people without.  

That’s due to this underlying immune deficiency. Since then, they’ve done studies looking at COVID specifically, and we have found lower rates of production of antibodies in individuals with CLL compared to regular, non-CLL controls. There have been a few different studies looking at this. I think the things that have been seen universally is that the CLL patients that are the most severely affected are those that are actively on therapy or have had recent anti-CD20. The CD20 drugs really wipe out the ability to make antibodies probably for a year, if not up to two years.  

The other drug class that can really hamper the ability to make antibodies are these BTK inhibitors. Then, venetoclax to some extent, it’s often paired with the CD20, so it’s hard to tease out the effect. But it likely hampers the ability to make antibodies as well, but just not as much as the CD20, which it’s often given concurrently with.  

CLL patients who have never had therapy can make a decent amount of antibodies, but still quite a bit less than an age-matched control. So, someone also your age without CLL. That was a lot of data based on the original two vaccine series. The Leukemia Lymphoma Society did a study that I actually referred a lot of my patients to, where they collected samples, looked at antibody levels, and they found that giving the booster did seroconvert a good amount of patients who were negative that then became positive for antibodies.  

That’s one of the reasons I’ve really encouraged the booster. This is now talking about the third shot. Now there’s this whole separate discussion about doing a fourth shot. I think the data’s a little too early to say it’s definitely helpful. But I think it’s certainly unlikely harmful. The vaccines don’t quite work as well. I feel very strongly they’re not harmful.  

Not to say any shot can’t cause some issue occasionally. But I think that’s very, very rare. I always encourage my patients to get the vaccine, but I separately say, “Gosh, I wouldn’t use this as an end-all cure because it may not work at its 100 percent efficacy level due to the underlying CLL, and worse when you’re under treatment.” 

Katherine:

We had another audience member send in a related question: “I’ve heard there is a treatment to help boost COVID antibodies. What is it and how can I get access to it?” 

Dr. Coombs:

I was going to bring that up actually, then I figured there was probably another question coming. I’m hugely enthusiastic about the drug that this person is speaking about. It’s called Evusheld. E-V-U-S-H-E-L-D. It got this emergency use authorization designation in December of 2021, so it’s pretty new. The idea behind this drug is that “Gosh, we know that not everyone is going to mount an effective immune response to vaccines, based on their own immune system, inability to make good levels of antibodies.”  

So, it’s two antibodies that were manufactured as this drug. So, it’s a drug that’s actually two different antibodies. It ends up being in two different vials, so you get two shots. It provides really remarkable protection against COVID. They’re long-acting antibodies, so they last for six months.   

The publication from the study that led to this being released showed an approximately 80 percent reduction in COVID for the people who got the shot as opposed to the people who got the placebo.  

Katherine:

It sounds like patients could ask their doctors about where they might be able to access this? 

Dr. Coombs:

Yeah. I think the best person to ask would be your CLL doctor. Because the drug, unless things have changed recently, it’s largely being focused for immunosuppressed individuals. Primary care doctors may not necessarily know a lot about it, but most oncologists are the ones who should have access to it. So, I would say ask your CLL doctor. If you’re in a smaller site that doesn’t have it, they may know in your geographic region where it could be gotten. 

Katherine:

As we close out this conversation, Dr. Coombs, I wanted to hear why you feel patients should be hopeful about the potential to thrive with CLL? 

Dr. Coombs:

There’s just so many reasons to be hopeful. CLL, I’d say more than – obviously it’s the cancer I’m focused on, but I think more than almost any other cancer has had advances that have really changed the lives of our patients in the last decade. And that’s only going to get better.  

We have therapies that work phenomenally well and can get you into remission, get the CLL under control, and let you just live your life as you wish; almost as though the CLL is not there. Though, it is in the background and your doctor can counsel you on special precautions needed. The drugs we have are phenomenal, but we only use them when we need them. Again, we don’t want to give you something you don’t need. But when you need it, the options we have are really phenomenal and they work well.  

They have some side effects, but I’d say they’re much better than the side effects of the older fashion drugs we used to use a decade-plus ago. The disease is there, we have better ways to control it, and I think there’s plenty of reasons to live your life, enjoy your life, thrive. We’ll take care of the CLL with all these tools in our toolbox when we need to.  

Katherine:

Dr. Coombs, thank you so much for joining us today.  

Dr. Coombs:

It’s been my pleasure, thank you.  

Katherine:

And thank you to all of our partners. To learn more about CLL and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us