Tag Archive for: personalized therapy

What You Should Know About DLBCL Treatment Side Effects

What You Should Know About DLBCL Treatment Side Effects from Patient Empowerment Network on Vimeo.

Once a patient begins diffuse large B-cell lymphoma (DLBCL) treatment, what side effects could they experience? Dr. Kami Maddocks, reviews potential side effects and how they may be managed.

Dr. Kami Maddocks is a hematologist who specializes in treating patients with B-cell malignancies at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Maddocks.

See More From The Pro-Active DLBCL Patient Toolkit

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Understanding DLBCL Treatment Classes

Understanding DLBCL Treatment Classes

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Emerging DLBCL Treatments That Patients Should Know About


Transcript:

Katherine:

What are the side effects that patients can expect with these treatments?  

Dr. Maddocks:

So, when they get the treatment, on the day they get it, there can be an infusion reaction to the rituximab or antibody therapies. So, the first treatment, that treatment is given very slowly and titrated up. If patients have a reaction, we stop it, treat the reaction, and then they’re able to continue therapy but again, that first day, it can take several hours for that one antibody to get in. And then, later, therapies are given at a more rapid pace.   

So, about 70 percent of people who react, it can be really almost anything. Some people get flushing, some people will get a fever, some people –have shortness of breath or their heart rate will go up. 

Katherine:

Okay. All right. Any other side effects? 

Dr. Maddocks:

Yeah. So then chemotherapy is meant to kill cells during the cell cycle. So, cancer cells divide more rapidly, chemotherapy is targeting them, but it also effects good cells in the body, specifically those that divide at a more rapid pace. The biggest risk of chemotherapy is infection.  

So, it effects the good white blood cells that fight infections. It can affect your red cells that carry your iron, gives you your energy. Or your platelets which help you to clot or not bleed when you get caught. So, infection is the biggest risk of chemotherapy. So, usually, with this regimen, that infectious risk is highest within the second week of treatment, that treatment is given every three weeks.  

So, we tell patients they should buy a thermometer, check their temperature, they have to notify their doctor or go to the ER if they have a fever. Besides infection, there’s a small percentage of patients who might need a transfusion. GI toxicity. So, nausea, vomiting, diarrhea, mouth sores, constipation, all of which we have good treatments for. So, we give medication before chemo to try to prevent people from getting sick and then give them medicine to go home with, if they have any nausea. We can alter those medications as time goes on, if they’re having any problems. So, we just need to know about it. Most patients will lose their hair with this regimen.  

It can affect people’s tastes, it can make their skin more sensitive to the sun, and then, less common but potential side effects are it can cause damage to the nerves. Or something we call neuropathy, which most often patients will start with getting numbness or tingling in their fingers and toes, and we can dose adjust if that’s causing some problems.  

And then, there’s a risk to the heart with one of the drugs. So, the heart should pump like this. The heart pump function can go down. So, we always check a patient’s heart pump function before they get their chemo, to make sure that they’re not at higher risk for that to happen.  

Katherine:

So, all of these approaches are used in initial treatment?  

Dr. Maddocks:

Mm-hmm. 

Katherine:

Okay. 

Emerging DLBCL Treatments That Patients Should Know About

Emerging DLBCL Treatments That Patients Should Know About from Patient Empowerment Network on Vimeo.

Are there new diffuse large B-cell lymphoma (DLBCL) treatment options? Dr. Kami Maddocks reviews developing research and approaches and what these advances could mean for patients.

Dr. Kami Maddocks is a hematologist who specializes in treating patients with B-cell malignancies at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Maddocks.

See More From The Pro-Active DLBCL Patient Toolkit

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Transcript:

Katherine:

Have there been any recent developments in how DLBCL is treated?  

Dr. Maddocks:

There had been recent developments. So, the CAR T-cell therapy, there is now three approved options for patients. And so, even patients who maybe are older and not considered candidates for a stem cell transplant because of other medical factors, might be able to get the CAR T-cell therapy. This is now, again, approved in the second line. There are a couple antibody drug conjugates, polatuzumab and loncastuximab, they target proteins called CD-79 and CD-19.  

And the polatuzumab’s the one that probably is going to be available for part of the front-line treatment in the future. There’s the antibody tafasitamab and lenalidomide. These are all approved therapies in the relapse setting. There are also therapies that are being studied and showing promising activity, which we think are probably likely to be approved in the future. There’s something particularly called bi-specific antibodies.  

So, this targets a protein on the tumor cell but also a protein on the T cell. So, remember I said the T cells aren’t functioning. So, this targets the protein on the lymphoma cell but then targets a protein on the T cell to engage it to attack the lymphoma cell. 

Katherine:

Right. Combination approaches?   

Dr. Maddocks:

Yeah. So, there are a number of combination approaches under study a lot of the therapies that I mentioned, like the bi-specific antibodies, the antibody drug conjugates. These are all therapies that – they have side effects – I hate to say they’re well-tolerated – they have side effects but their side effects are such that they can be combined with other agents, that have different toxicities that are combined with each other. And so, there’s a lot of ongoing trials looking at combining these. There’re also oral targeted therapies that target proteins that are known to help the lymphoma cells survive and these are modulator therapies, BTK inhibitors, other inhibitors, that are being evaluated and used in combinations.  

Katherine:

Thanks, Dr. Maddocks. That’s really helpful information. 

Is My DLBCL Treatment Working? What Happens If It Doesn’t Work?

Is My DLBCL Treatment Working? What Happens If It Doesn’t Work? from Patient Empowerment Network on Vimeo.

Diffuse large B-cell lymphoma (DLBCL) expert Dr. Kami Maddocks describes how a treatment’s effectiveness is evaluated and reviews the options available for refractory patients.

Dr. Kami Maddocks is a hematologist who specializes in treating patients with B-cell malignancies at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Maddocks.

See More From The Pro-Active DLBCL Patient Toolkit

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Transcript:

Katherine:

So, how do you know if a treatment is working?  

Dr. Maddocks:

So, as far as evaluating treatment, you get a scan before you start treatments, so we know where all the lymphoma is at. And then, typically, you get some sort of scan in the middle of treatment, and then after, you complete your six cycles of treatment. Or for early stages, sometimes patients will get less than six cycles. So, we get scans to make sure it’s working. So, you can tell by those things, how much has gone, hopefully all of it has gone by the end. Occasionally, patients that had a lot of symptoms to start with, their symptoms will go away, and then they’ll start coming back.  

This is less common, because the majority of patients do respond to chemotherapy. It’s less common to get patients who are what is called refractory, meaning they don’t get any response to therapy. So, occasionally they’ll note symptoms but a lot of times, we’ll see something on that mid-therapy or end of therapy scan, if it’s not going to make it all go away.  

Katherine:

So, if a treatment doesn’t work, what happens then?  

Dr. Maddocks:

If treatment doesn’t work, it depends a little bit – and now it depends a little bit on the timing of that treatment not working. So, it used to be that patients who were eligible for treatment, no matter if it didn’t work right away or if it put them into what we call a remission, so there’s no evidence of disease and then it relapsed, they would have the option of further chemotherapy and then an autologous stem cell transplant. So, a bone marrow transplant where they donate their own cells.  

If they were in a good enough health or if they were not – to do that, you have to donate your own bone marrow cells and as we age, we make less bone marrow cells. So, once you reach a certain age, your body can’t produce enough cells to donate to a transplant. In those patients, we offer them less aggressive chemo options, which were not known to be curable but could put them into remission again, for a while. More recently, there has been some that chimeric antigen receptor T-cell therapy that I mentioned where you actually donate your own T cells. So that’s –. And your lymphoma is of your B cells.  

Your T cells are in another immune cell that should recognize that lymphoma is bad and attack it, and they’re not functioning properly. So, you donate your own T cells, and they’re sent off and reengineered to target a protein on the tumor. Then, you get those cells back, and they’re meant to target the lymphoma and kill the lymphoma cells.  

So, that is now an approved therapy for patients who don’t achieve the remission – so, who’s first chemo doesn’t work or if they relapse within a year of completing chemo. So, that’s a possibility. The chemo and transplants a possibility. Or there’s other approved therapies now, that can be given as second options or third or later options, which have been shown to keep patients in remission for a while.  

Katherine:

Dr. Maddocks, you touched up on this a moment ago, but what are the approaches if a patient relapses? What do you do?   

Dr. Maddocks:

So, you would rework them up if they relapsed. Similar to that, if they relapse within a year and they have access to the CAR-T and they’re healthy for that, then that’ll be an option. The second type of chemotherapy in the transplant. So, you can’t just go straight to a transplant. You have to get a different type of chemotherapy to try to get the disease under control again, before you would go to a transplant.  

Or there’s a number of other targeted therapies that are approved. So, there’s other – I talked about rituximab (Rituxan) is given in the first line, that targets a CD-20 protein, there’s an antibody that targets a CD-19 protein that’s given out in relapse. There’s another antibody drug – there’s actually two antibody drug conjugates. So, an antibody that targets the protein on the cells that are attached to a chemo, that’s given. Or there’s different chemotherapy and then even some oral therapies.  

Katherine:

Okay. So, there’s a lot of different options available for people.  

Dr. Maddocks:

Correct. And there’s always clinical trials. So, there’s always the option to find something where we’re studying some of these newer therapies. They’re therapies in combination.  

Understanding DLBCL Treatment Classes

Understanding DLBCL Treatment Classes from Patient Empowerment Network on Vimeo.

Dr. Kami Maddocks reviews diffuse large B-cell lymphoma (DLBCL) treatment approaches, including options for patients who are considered high-risk or who have relapsed. Dr. Maddocks goes on to review which factors are considered when selecting a therapy and the potential for curative treatment.

Dr. Kami Maddocks is a hematologist who specializes in treating patients with B-cell malignancies at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Maddocks.

See More From The Pro-Active DLBCL Patient Toolkit

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Transcript:

Katherine:

Let’s turn to treatment options. Is a person with DLBCL treated right away?  

Dr. Maddocks:

They’re treated pretty quickly after the diagnosis. So, typically, when somebody has a diagnosis, they undergo a number of different tests, including lab work, imaging work, sometimes for their biopsies.  

So, that information is gathered over days to sometimes a few weeks process. Then, when you have all that information, you go over the results, go over the treatment at that time. So, it’s typically treated not within, usually, a day of diagnosis but it’s not something that you spend weeks or months before treating.  

Katherine:

Yeah. What are the different types of treatments available?  

Dr. Maddocks:

So, the diffuse large B-cell lymphoma is treated with chemotherapy and immunotherapy. So, a combination of an immune antibody therapy and chemotherapy. There is a role in some cases for radiation, but never just radiation alone and never just surgery alone. So, there’s always what we call a systemic treatment so, a treatment that goes everywhere. Because this is considered a blood cancer, it’s a cancer of those cells, it can really spread anywhere.  

And so, just cutting it out with surgery or just radiating the area doesn’t treat everything, even if you can’t identify it.  

Katherine:

Can you get specific about some of the treatment classes?   

Dr. Maddocks:

Yeah. So, the most common treatment for diffuse large B-cell lymphoma is a chemo immunotherapy called R-CHOP. So, this is three chemotherapies and antibody therapy that’s direct called rituximab (Rituxan) that’s directed at a protein on the lymphoma cells. And then, a steroid called prednisone, given with the chemo and then for a few days after. There was a study that recently showed an improvement with switching one of those drugs with another immunotherapy that’s an antibody conjugated to a chemo drug. But that’s not yet been approved. There are clinical trials available. So, looking at these treatments that might be new or combining therapies with this standard treatment.  

And then, very occasionally, there are certain features of diffuse large B-cell lymphoma. There are particular few different subtypes that are classified a little bit differently, that are treated within an infusional therapy called Dose Adjusted R-EPOCH.  

Katherine:

What about stem cell therapy? Is that used?  

Dr. Maddock:

Stem cell therapy is used in the relapse setting. So, if a patient doesn’t go into a remission or if they relapse after achieving a remission with their chemotherapy, then stem cell transplant is an option. So, there are actually two different types of stem cell transplant. One from yourself and one from somebody else. In lymphoma, we typically do one from yourself, where you donate your own cell before. But we don’t use that as part of the initial treatment.   

Katherine:

So, if somebody is high risk, Dr. Maddocks, is the approach different for them? 

Dr. Maddocks:

So, it depends. We define high risk in different ways. So, there’s a specific type of lymphoma called double hit lymphoma, where there’s a few chromosomal translocations associated with the lymphoma, that we give a little more aggressive chemo immunotherapy regimen. There are also other subtypes, including a rare type of lymphoma called primary mediastinal B-cell lymphoma. Again, categorized a little bit different but sometimes included as a large cell lymphoma. We also give that treatment for.   

Katherine:

Okay. So, there’s a lot of different options available for people.  

Dr. Maddocks:

Correct. And there’s always clinical trials. So, there’s always the option to find something where we’re studying some of these newer therapies. They’re therapies in combination.   

Katherine:

Is a cure possible?  

Dr. Maddocks:

Yes. A cure is possible. When you look at patients who are treated with initial chemotherapy, we cure somewhere between 60 percent to 70 percent of patients with the initial chemotherapy. If patients’ relapse, depending on their age and their condition, they’re candidates for other therapies.  

And therapy including other chemo and stem cell transplant is potentially curable in some patients. And then, there’s a newer therapy called chimeric antigen receptor T-cell, or CAR T-cell therapy, which also looks like it’s curing a subset of patients who relapse or don’t respond to initial therapy.  

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.

See More from Thrive CLL

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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. 

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

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

What should you consider when choosing acute myeloid leukemia (AML) care and treatment? Dr. Eytan Stein reviews factors that help guide care decisions for AML, discusses the goals of treatment as well as treatment options available, and shares tools for taking an active role in your care.

Dr. Eytan Stein is a hematologist oncologist at Memorial Sloan Kettering Cancer Center and serves as Director of the Program for Drug Development in Leukemia in Division of Hematologic Malignancies. Learn more about Dr. Stein, here.

See More from Thrive AML

Related Resources:

Thriving With AML: What You Should Know About Care and Treatment Resource Guide

Shared Decision-Making, Advice for Partnering With Your AML Team

Which Tests Do You Need Before Deciding on an AML Treatment Path


Transcript:

Katherine Banwell:  

Hello, and welcome. I’m Katherine Banwell, your host for today’s webinar. Today’s program is about how to live and thrive with AML. We’re going to discuss the goals of AML treatment and how you can play 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. Eytan Stein. Dr. Stein, welcome. Would you please introduce yourself?  

Dr. Stein:

Thanks so much. My name is Eytan Stein. I work as an attending physician on the leukemia service at Memorial Sloan Kettering Cancer Center in New York City.  

Katherine Banwell:

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

Dr. Stein:

Thank you for having me.  

Katherine Banwell:

Since this webinar is part of Patient Empowerment Network’s Thrive series, I thought we could start by getting your opinion on what you think it means to thrive with AML. 

Dr. Stein:

Yeah, so thriving with AML I think can mean different things to different people. Thriving with AML can mean when you have the disease, really having the fortitude to get through the treatment that you’re being given because sometimes that can be tough.  

And sometimes, it’s not easy. But the people who are thriving are the ones who are able to discuss with their doctors what their treatment is, what the side effects of that treatment might be, how to minimize those side effects, and how to get through that treatment so that not only do they feel better physically but can feel better emotionally and ultimately, hopefully go into a complete remission. 

Katherine Banwell:

Thank you for that, Dr. Stein. I think that helps guide us as we continue this conversation. Getting appropriate AML care is part of thriving, and when we consider treatment options, it’s important to understand the goal of treatment. So, how would you define treatment goals for patients? 

Dr. Stein:

Yeah, so the treatment goals for patients really come in different forms. I think fundamentally what everyone wants is everyone wants to go into a complete remission and be cured of their disease. And certainly, that’s an overarching goal that we aim to achieve with our treatments. But there are other goals that I think are important too to various patient populations, depending on what stage of life they’re in.  

Are they 85 years old or 90 years old and have lived a long, full life? And their goal might be to improve their blood count so they don’t need transfusions so frequently. And they might be able to go to that grandchild or great-grandchild’s wedding or other life event. There are other patients for whom the goal might be, very discreetly, just to get to that next step in their treatment.   

That next step in their treatment might be a bone marrow transplant. The next step in their treatment might be some more therapy. But I think overall as a doctor, our goal is always to do our best to get our patients into a complete remission and cure them while maintaining the best quality of life for our patients.  

Katherine Banwell:

What do you think is the patient’s role in setting treatment goals? 

Dr. Stein:

Well, it’s really important for the doctor to explore the goals of treatment when they first meet with the patient. I don’t think doctors should assume that all patients come into that first visit with the same goals. And what those goals are, I think, may differ a little bit from patient to patient. And it’s really important for the patient to express overtly what their goals are, what they want to achieve from the treatment. You know, I have some patients who come in to me and say, “My goal is to be cured and be alive for the next 30 years” or 40 years or 50 years.  

And I have some patients that come into treatment, and they say, “You know what, I have had a very, very long life, and I just want the best quality I can have for as long as I can possibly have it.” 

Katherine Banwell:

Yeah, that’s great advice. Thank you. As we move into the discussion about treatment for AML, let’s define a couple of terms that are often mentioned in AML care. What is induction therapy?   

Dr. Stein:

Yeah, so induction chemotherapy refers really to a type of chemotherapy that tends to be quite intensive, so strong chemotherapy that patients receive in the hospital setting. That induction chemotherapy typically requires a hospitalization of three to four weeks, sometimes a little bit longer, as the patient gets their treatment during the first week or so and then they’re recovering from the effects of that treatment during the next three weeks in the hospital.  

Katherine Banwell:

Okay. What is consolidation therapy? 

Dr. Stein:

Ah. So, a patient first gets induction chemotherapy. If they achieve a complete remission, so their disease goes away, that’s great. We know their disease seems to be gone. But we also know that patients relapse. So, if patients relapse, it means their disease wasn’t really gone. It’s just that we couldn’t find it. It was hiding somewhere.  

So, consolidation chemotherapy is chemotherapy that is given after a patient is in complete remission in an effort to kill any residual leukemia cells that may be hiding in the body, that we can’t see in our bone marrow biopsies, in an effort to deepen the remission that we’ve achieved during induction.  

Katherine Banwell:

Okay. Are there any other terms that patients should be familiar with? 

Dr. Stein:

There are. You know, there are a lot of other terms that patients should be familiar with. I’ll just touch on one because it can get complicated. We now have for acute myeloid leukemia, a type of therapy that goes beyond induction and consolidation called maintenance therapy.  

Maintenance therapy is when a patient is done with induction, done with consolidation, and the question is, can you give them something that is easy to take, relatively non-toxic, that they can take for a prolonged period of time, to also help prevent relapse? Maintenance therapy has been really a backbone of the treatment of a different kind of leukemia called acute lymphoblastic leukemia, which happens primarily in children for many years. Maintenance therapy is also now a backbone of therapy for a different kind of blood cancer called multiple myeloma. And very recently, only within the past year to two years, we’ve incorporated maintenance therapy for AML for certain groups of patients.  

Katherine Banwell:

Okay. What are the treatment types available to AML patients? You mentioned chemotherapy. What else is there? 

Dr. Stein:

Yeah, so if I was having this discussion with you, even when I first started my career back in 2013, all I would’ve been talking to you about was induction chemotherapy and maybe a lower-dose chemotherapy called hypomethylating agents.  

I think one thing that really needs to be recognized is that the advances we’ve made for the treatment of acute myeloid leukemia, over the past 10 years, have been just remarkable. We’ve had a number up to nine drug approvals over the past 10 years, and those therapies fall into the following categories.  

We now have therapies outside the strong induction consolidation we talked about. We have therapies such as targeted therapies that target specific gene mutations that are present in patients with acute myeloid leukemia. Those are often oral therapies that patients can take at home. And we have very effective therapies for older patients who usually can’t handle the side effects of induction chemotherapy. That’s the combination of a type of drug called a hypomethylating agent with a very, very powerful targeted drug called a BCL-2 inhibitor.  

One of those drugs, that drug is called venetoclax (Venclexta). That’s the one that’s FDA-approved. And the combination of those hypomethylating agents and venetoclax, has really changed the paradigm for how we treat older patients with acute myeloid leukemia, led to many patients who have been able to live much longer than they would have before this therapy came about.  

You know, there are other therapies that are in development, but I don’t know if we’ll end up talking about that a little bit later. But there are therapies such as immunotherapy, which has gotten a lot of press for other kinds of cancers, like one cancer called the rectal cancer, that aren’t yet approved for acute myeloid leukemia but are being developed for acute myeloid.  

So, the future of acute – the current treatments for acute myeloid leukemia are dramatically better than they were 10 years ago, and I would anticipate that we’re going to continue to see these kind of advances over the next 10 years.  

Katherine Banwell:

And we are going to talk further about that in a couple of minutes. What about stem cell transplant? Who might be right for that? Who might be eligible? 

Dr. Stein:

Yeah, so let’s go back to the discussion a little bit about consolidation chemotherapy. So, when you have a patient that gets induction chemotherapy or gets any therapy – it doesn’t have to be chemotherapy – to put their disease into remission, for a large group of patients, we think that the best way to cure their disease is to do something called a stem cell transplant.  

So, what’s a stem cell transplant. What it is not is like a heart transplant or a liver transplant, which patients often don’t realize.  

So, it’s not a procedure where an organ is being transplanted through a surgical procedure. What it is is it’s acknowledging that the cause of acute myeloid leukemia is that the most primitive cells in the bone marrow, called the stem cells, are the cause of the disease. And the chemotherapies that we give patients to get them into remission don’t always eradicate those bad stem cells.  

So, what we’re able to do once a patient is in remission is we try to get them new stem cells. How do you get a patient new stem cells? Well, you go to a donor, and there’s a donor bank of people who have volunteered to donate stem cells to patients with acute myeloid leukemia. You go to the donor bank, and then you give chemotherapy to the patient to sort of wipe out their bad stem cells, and then you give them new stem cells that will hopefully permanently eradicate the disease.  

What ends up happening is that a large group of patients with acute myeloid leukemia end up being referred for a stem cell transplant. The reason is twofold. You know, it used to be – I keep talking about the past. I’m getting older, and so now I can talk about the past.  

Katherine Banwell:

We’ll talk about the future in a couple of minutes. 

Dr. Stein:

Yeah. So, it used to be that stem cell transplants were really reserved to people less than 65 years old.  

But our advances in our ability to do stem cell transplants has allowed for us to now successfully do stem cell transplants on patients, even into their upper 70s and sometimes even at the age of 80.  

Katherine Banwell:

Wow, okay. That’s great. Where do clinical trials fit in to all of this? 

Dr. Stein:

Ah. So, clinical trials are extraordinarily important for a variety of reasons. Clinical trials are important because the only way we make advances on a societal level in the treatment of acute myeloid leukemia is by patients who are willing to participate in clinical trials. All of the – because these are trials that are testing new therapies with the goal of improving the survival and the quality of life of patients with acute myeloid leukemia. All these drugs I just talked about that have been approved over the past 10 years, they never would’ve been approved if patients hadn’t agreed to participate in clinical trials. So, that’s something that’s number one that’s very important.  

But on a – forget the societal level for a second. On a patient-specific level, a clinical trial can potentially benefit a patient because it offers a patient access to a new, exciting therapy that may really help in improving their outcome of having acute myeloid leukemia.  

Katherine Banwell:

Yeah. You mentioned emerging therapies. What are some of those? 

Dr. Stein:

Oh, there’s so many. So, it’s hard to talk about all of them, but I think there are targeted therapies – I think if you sort of break them up into sort of broad buckets, there are new targeted therapies that are being developed for subsets of patients with acute myeloid leukemia. One of the ones I’ve been working on pretty heavily over the past few years is a kind of drug called a menin inhibitor. This is an oral medication that is given to patients of acute myeloid leukemia who have certain genetic abnormalities, specifically either a mutation in a gene called NPM1, or a what is called a rearrangement in a gene called MLL.  

So, that’s a group of – that menin inhibition seems to be extraordinarily effective in treating patients, at least from the early data, for those specific subtypes of acute leukemia.  

The other therapies that are really getting a lot of play now are the immunotherapies, which I mentioned a second ago. There are immunotherapies that work to – called bispecific immunotherapies where what happens is it works to harness the immune system to kill the cancer cells. You may have heard a lot about CAR T-cell therapy, which is another way of harnessing the immune system and engineering immune cells to target acute myeloid leukemia cells. And the other thing I want to point out is that even if you don’t have a new therapy against a new target, you can imagine now that we’ve got all these 10 new approved drugs.  

But what we’re trying to figure out – one of the things we’re trying to figure out over the past few years has been what’s the best way to give these new drugs? What kind of combinations can you put them in that might make things even better? Maybe you should give two of those drugs first and then give another drug afterwards. And a lot of the research that’s being done now is being done to understand the best sequencing and combinations of drugs with the drugs that we already have approved. 

Katherine Banwell:

Great. All patients are different, of course, and what might work for one person might not be appropriate for another. How do you choose which treatment is right for a patient? 

Dr. Stein:

So, it’s an individualized decision. So, what you’re talking to the patient, as we talked about at the very beginning, is you really need to understand the patient’s goals for treatment. You need to understand the anticipated benefit of the treatment that you’re offering and need to understand the side effects of the treatment. 

So, and that sort of becomes the puzzle that you work with the patient at putting together. That is how well do I expect this treatment to work? What are the potential side effects of the treatment, and what are the patient’s goals? And when you sort of lay all those different pieces out, you then usually come up with something that becomes pretty clear what the best thing to do is.  

So, I’ll give you just a very concrete example of this. Sometimes, we have treatments where the medical data would suggest that they might work as well as one another, right? There’s no clear difference between each of the two treatments. But maybe one of the two treatments requires you to be in the hospital, and one of the treatments allows you to be at home.  

So, that’s an important discussion to have with the patient because some patients, believe it or not, want to be in the hospital, because they’re worried about being at home and having to manage this all themselves. Some patients don’t want to be in the hospital. Some patients want to be at home, because they’re scared of the hospital, or they’re worried the food’s going to be terrible.  

And then, that would be important in helping the patient make the decision for their treatment.  

Katherine Banwell:

Right. You mentioned earlier, Dr. Stein, the difference in ages and how you would treat different people depending on their age. So, when you’re choosing a treatment, you obviously look at age. What else? Things like comorbidities?  

Dr. Stein:

Yeah, so age, so I’m not ageist. So, it’s more that as people get older – and this is just a fact of life – as everyone gets older, their organs don’t work quite as well anymore, right? Things start breaking down as you get older. So, certain treatments aren’t appropriate for older people because the treatments a younger person, because their organs are working at 100 percent, may be able to handle it, while an older person, where their organs might only be working at 60, 70 percent, the treatment might not be as good of a choice for them. 

So, that’s what I mean. So, as people age, their comorbidities increase. So, we always look at comorbidities, and if you had an 80-year-old that was running marathons, I might think about their treatment differently than an 80-year-old who is not running marathons. But most 80- and 85-year-olds aren’t running marathons, so that’s why we sometimes think about their treatment differently.  

Katherine Banwell:

Yeah. Why is identification of genetic markers essential before choosing treatment?   

Dr. Stein:

Because when you know the genetic markers, you can target the genetic abnormalities, sometimes with specific targeted therapies, with therapies that fit like a key in a specific lock. And those targeted therapies have been shown, in some cases, to improve the survival of the patients, without much cost, without much toxicity. So, I’ll give you an example of this.  

There is a very common genetic abnormality in patients with acute myeloid leukemia called the FLT3 or FLT3 mutation. When you have that mutation, there is a targeted therapy that targets the FLT3 mutation called midostaurin, and it’s been shown in a very large clinical trial that the addition of the targeted FLT3 inhibitor midostaurin in combination with chemotherapy leads to better overall survival than chemotherapy alone.   

So, you need to know that information because you want to give your patient the best chance at beating the disease. And that’s why it’s also important to try to get this information back quickly. You know, no one wants to be sitting around waiting for four weeks to find out if they’ve got a specific mutation. And we’ve gotten better. I think medical centers generally have gotten better at getting this mutational information back to their doctors relatively quickly. 

 Katherine Banwell:

Does every patient get this standard testing? 

Dr. Stein:

It is – does everyone get it? I don’t know. But “Should everyone get it?” is, I think, the important question. Yes, everyone should get this testing.  

 It is incorporated into the NCCN and National Comprehensive Cancer Network and European Leukemia Net guidelines. It is important not only because you can think about targeted therapies, but it is also important for prognostic reasons, meaning that certain mutations lead to a higher risk of relapse, and those mutations in a patient might lead me to recommend a stem cell transplant, which is sort of the most intensive thing we can do to help prevent a relapse, while other mutations, which might be “favorable”, in quotes, they might lead me not to recommend a stem cell transplant.   

So, I think this mutational testing is the standard of care and should be done in every patient with newly diagnosed acute myeloid leukemia.  

Katherine Banwell:

Once treatment has begun, Dr. Stein, how do you know if it’s working? 

Dr. Stein:

So, that’s a good question. So, the good thing about acute myeloid leukemia when it comes to understanding what’s going on, you know, it’s a disease of the bone marrow cells. And we do bone marrow biopsies to see how things are doing. But no one likes a bone marrow biopsy. It can be a somewhat uncomfortable procedure.  

Katherine Banwell:

How often would a patient need to have a biopsy?  

Dr. Stein:

Yeah, so they have bone marrow biopsies at diagnosis, and then they often will have bone marrow biopsies two weeks to a month later.  

And then, if they’re in remission, basically any time you think if you want to check to see if they’re in remission or if you suspect the patient is relapsing. Then, you would do a bone marrow biopsy. But what I was getting at is that but you have blood. And the blood is kind of like the bellwether of what’s going on in the bone marrow.  

So, the analogy I use for my patients is, you know, when you’re driving your car and you have – you know, you don’t open the hood every day to make sure the car is running okay. You know, you’re driving your car, and if your car starts making a funny clinking sound, that’s when you open the hood.   

So, the blood is like the clinking sound. If you see something going wrong in the blood, that’s when you know you’ve gotta open the hood and look under the hood. If the car is running just fine and you don’t see anything wrong in the blood, using the analogy, maybe you don’t need to do a bone marrow biopsy. 

Katherine Banwell:

What if a treatment isn’t working? What if it stops working or if the patient relapses? What do you do then?  

Dr. Stein:

Yeah, so when a patient relapses, which unfortunately happens more than we want it to, it’s important No. 1 to do another bone marrow biopsy and at that point, do that mutational testing again because the mutations that are present at the time of diagnosis are not necessarily going to be present at the time of relapse, and sometimes, a new mutation might occur at the time of relapse. And again, what that mutational profile shows can help determine what the next best treatment for the patient is. There might be standard-of-care therapies. More chemotherapy might be recommended.  

When a patient relapses, I usually – excuse me – try to get them on a clinical trial because that’s the point where I think clinical trial drugs really have potentially major benefit for the patients, to help get them back into remission. 

Katherine Banwell:

Why is it essential for patients to share any issues they may be having with their healthcare team, specifically, sharing their symptoms and side effects?  

Dr. Stein:

Well, it’s important because we want to help you. I mean, I think that’s what it comes down to. All of us, whether it’s your doctor or your nurses or your nurse practitioner or physician’s assistant or anyone who is part of the healthcare system, we went into this business to help people. I mean, we knew what we were getting into when we went into this, and we want to help people. And one of the ways you help people is you help with their symptoms. So, if you’re not feeling well, you call up, and you say, “I’m not feeling well,” we can help you with that. You shouldn’t suffer in silence.  

I sometimes have patients who will say to me, “Oh, I was going to call you, but I didn’t want to bother you.” You’re not bothering us. This is what – it’s not like you’re calling and asking for mortgage advice, right? This is what we do. So, it’s very important to call us because the other thing is that you’re going to be more – it’s more likely that you’ll be able to complete your treatment if we manage the side effects that you’re having rather than just ignoring them.  

Katherine Banwell:

Yeah, that’s great advice. With more oral therapies becoming available, patients now have a role in self-administering their treatment. So, what happens if a patient forgets to take a medication? Does that impact its effectiveness? 

Dr. Stein:

The easy answer to that question is probably not. You know, if you forget to take a medication for three weeks, that’s not a good thing, but if there’s a – you know, this happens all the time, right?   

You’re busy, and you just forget. If you forget to take a medication one night or one day, it almost certainly is not going to make a huge difference. Having said that, you shouldn’t see that as license to not be careful. So, it is important to try. So, set an alarm; put out a pill container do the kinds of things that can help you.   

The other thing, there is a certain what I would call pill fatigue that sets in. Often, patients with AML are taking multiple medications at multiple times a day, and it can be hard. And at my center, we have pharmacists who do a lot of different things, but one of the things they can help with is sort of streamlining patients’ pill burden to make it easier for them to remember and to take the medications when they’re supposed to take them.  

Katherine Banwell:

When a patient does forget to take a dose or even a couple of days’ doses, should they call their healthcare team and let them know? 

Dr. Stein:

Yes, always call. Always call.  

Katherine Banwell:

Okay. I want to make sure we get to some of the audience questions. These were sent to us in advance of the program. Let’s start with this one from Patrick. He writes, “Are there any clinical trials looking at maintenance therapy for the AML patients, especially older patients?” 

Dr. Stein:

Yes, there are a number of clinical trials that are looking at maintenance therapy for older patients with acute myeloid leukemia. Some of those trials are maintenance therapies with targeted agents that are against specific mutations. Some of those trials are clinical trials with more broadly active agents that might be able to be used as maintenance therapy, so yes. Maintenance therapy is something that is really coming to the fore, and I would encourage you to seek out trials that might offer maintenance therapy.

Katherine Banwell:

Aaron sent in this question: “What are the most promising new effective drugs on the verge of being approved by the FDA, and what do they do?” 

Dr. Stein:

Yeah, so I’ll just mention the one I mentioned a second ago, and that’s the class of drugs called menin inhibitors. I wouldn’t quite say they’re on the verge of being approved by the FDA, but I think that they’re very, very powerful drugs that within the next two or three years, they will likely be approved by the FDA if the early clinical trials continue to pan out. And those are drugs that at least in the early experience, seem to be specific for patients with these NPM1 mutations or these MLL rearrangements. And your doctor will know what those are if you ask them, “Do I have an NPM1 mutation, or do I have an MLL rearrangement?” 

Katherine Banwell:

Thank you for that, Dr. Stein. And to our viewers, please continue to send in your questions to question@powerfulpatients.org, and we’ll work to get them answered on future programs.   

What advice do you have for patients to help them feel confident in speaking up and becoming a partner in their own care? 

Dr. Stein:

My advice is, speak up. You just speak up. It’s very important. It’s your – you know, at the end of the day, this is a disease that you are experiencing. Your doctor is there to partner with you and to guide you, but it’s your body. It’s your disease, and you need to be very vocal in what you’re experiencing and advocate for yourself.  

Katherine Banwell:

If a patient has difficulty voicing their questions or concerns, are there members of the support staff who could help?  

Dr. Stein:

Most centers have a social worker on staff that can help them out. I highly, highly encourage all of my patients to meet with a therapist or a psychologist that specializes in taking care of patients with cancer. I have become more vocal about this that I see. Really, it’s probably the best thing a patient can do for themselves, and there’s no downside. If you don’t like it, you don’t have to go back. Do one appointment and not go back. But that can be extremely helpful, extremely helpful.  

So, it’s important in both ways. You need to alert your doctor that you might be feeling one way, but I think it’s also on the doctor to sort of take visual cues from the patient when they see them to understand what they might need and to make those kind of recommendations.  

Katherine Banwell:

Yeah. As we close out our conversation, Dr. Stein, I wanted to get your take on the future of AML. What makes you hopeful?  

Dr. Stein:

Oh, so many things make me hopeful. I mean, we understand this disease so much more than we understood it even 10 years ago. There are all sorts of new treatments that are being developed. We’re improving the survival of our patients with the new treatments that have already been approved over the past 10 years. And I really think the golden age of AML treatment is upon us, and I really think that – and some people might think I’m crazy – but I really think that by the time I’m done with this, you know, one day, I’ll get too old, and I’ll decide I need to go retire and spend time with my family. But I think by that time, we’re going to be curing the vast majority of our patients. 

Katherine Banwell:

That’s so positive. It’s great to hear that there’s been so much advancement and that there’s so much hope out there for AML patients. I want to thank you so much for taking the time to join us today, Dr. Stein.  

Dr. Stein:

Okay, thank you. It was really nice to be here.   

Katherine Banwell:

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

Follicular Lymphoma Research and Treatment Updates

Follicular Lymphoma Research and Treatment Updates from Patient Empowerment Network on Vimeo.

Dr. Matthew Matasar shares follicular lymphoma treatment and research highlights from the 2022 American Society of Clinical Oncology (ASCO) meeting.

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:

Cancer researchers recently came together to share findings at the annual American Society of Clinical Oncology meeting also known as ASCO. Are there highlights from the meeting that follicular patients need to know about? 

Dr. Matasar:

The pace of innovation in follicular lymphoma is absolutely breathtaking. And the treatment options that are being explored and coming available to us now are really extraordinary. And they’re extraordinary because they offer this unparalleled possibility of very highly effective and less toxic, fewer less long-term and short-term side effects than prior options may have afforded us.  

This is particularly true in two general areas of investigation. The first is what we call immunotherapy or treatments that are designed to leverage your own immune system’s ability to kill cancer cells. And the second is what we would call targeted therapies, treatments that are designed to attack a specific enzyme, or protein, or pathway that is relied upon by follicular lymphoma cells to survive and to grow.  

Immunotherapy for follicular lymphoma is perhaps the most exciting of everything right now. And there’s a class of agents that are called bispecific antibodies. These are antibodies or proteins that have two specific regions on them, one that binds onto the surface of the follicular lymphoma cell and one that serves as sort of an activator or tractor beam for your own body’s healthy T cells. So, it attaches to the B cell. It drags over and stimulates T cells, and says, “Get them, guys.” And it causes your own body’s T cells to recognize, attack, and kill lymphoma cells for you.  

There’s a number of these agents that are in active clinical development. And we say updates at ASCO this year showing that these agents are very effective at treating follicular lymphoma even when prior chemotherapy agents have been unsuccessful at achieving durable remissions with really very little toxicity particularly after the first month of treatment is under your belt.  

Katherine Banwell:

What are you excited about when it comes to follicular lymphoma research? 

Dr. Matasar:

What I’m excited about is the overall pace of innovation. We have more drugs that are approved in the treatment of this illness in the last five years than in the 20 years that preceded it. And we have more options that we expect to become available over these next three years than were approved in the last five, immunotherapy, targeted therapy, therapies that modified the genetic signatures of the cells, treatments that used living cells and genetically modified those cells to attack your lymphoma, combinations of immunotherapies and targeted therapies.   

The innovation is really extraordinary, and it gives me tremendous hope that over these upcoming years, I’m going to have even more choices to offer my patients with follicular lymphoma, ways to improve their quality of life, the length of their life, and to find better ways to manage this illness.  

Katherine Banwell:

That sounds so promising. 

Why Is It Important for Follicular Lymphoma Patients to Be Empowered?

Why Is It Important for Follicular Lymphoma Patients to Be Empowered? from Patient Empowerment Network on Vimeo.

Lymphoma expert Dr. Matthew Matasar explains why it is important for patients with follicular lymphoma to feel empowered in their care and shares how he empowers his own patients.

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:

How do you empower patients? 

Dr. Matasar:

For me, empowering patients isn’t something that you do. It’s just inherent to the practice of medicine and taking care of people with lymphoma. There’s lots of ways that you can think about this, but one of my standard lines when I’m talking with patients is that I’ll say that this is their climb.  

They’re the mountain climber, and I’m just the sherpa. I’m the one lugging the bags and trying to help point out the paths. But this is their climb, and it’s about them, and it’s never about me.   

Katherine Banwell:

Why is it important to empower patients? 

Dr. Matasar:

It’s inherent. It’s obvious at some level that you have to empower patients because the care of patients, the care of people, is about people. It’s not about the doctor, or the nurse, or the clinical trial, or the drug, or pharma, or the hospital. It’s about you. I can only be as good a doctor as I am at listening to you or to my patient. And this is extremely clear with diseases like follicular lymphoma, which have such tremendous variety in terms of how it affects people, variety in terms of the options that I have to offer as treatments. It’s an extremely individualized and personalized situation.  

So, if it’s not about you, and your goals, and your preferences, and your priorities, then I can’t do my job right.  

Katherine Banwell:

Right. You need as much information as possible from the patient.  

Dr. Matasar:

It’s all about the patient. And the clearer that I understand my patient’s personality, priorities, preferences, family situation, all of that stuff, the better job I’ll be able to do at helping them pick the right path forward.  

What Do DLBCL Patients Need to Know About Treatment and Research?

What Do DLBCL Patients Need to Know About Treatment and Research? from Patient Empowerment Network on Vimeo.

How have diffuse large B-cell lymphoma (DLBCL) treatment options evolved? Lymphoma expert Dr. Matthew Matasar reviews current treatment options for DLBCL and shares his perspective on where research is heading.

Dr. Matthew Matasar is a lymphoma expert at Rutgers Cancer Institute. To learn more about Dr. Matasar, visit here.

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Transcript:

Katherine Banwell:

Dr. Matasar, what are the types of treatments currently available to treat DLBCL? 

Dr. Matasar:

So, DLBCL, or diffuse large B-cell lymphoma, is the most common type of aggressive B-cell non-Hodgkin’s lymphoma in America and really around the world. Aggressive lymphomas are a double-edged sword. They tend to grow quickly over weeks to months, and they tend to make people feel sick if left untreated, but they’re potentially curable in many although not all patients.  

We now have a growing body of treatment options available to maximize the changes of cure and to minimize short and long-term risks in patients diagnosed with aggressive B-cell lymphomas.  

The first recent innovation is a treatment program that seems to improve upon the standard of care treatment called R-CHOP, R-C-H-O-P, which is a combination of chemotherapy and immunotherapies in the treatment of newly diagnosed diffuse large B-cell lymphoma. And this new regimen substitutes out one of those medicines, the O, which is a medicine called Oncovin, or vincristine, with a newer medicine that has a long name called polatuzumab vedotin, or pola for short. And we found in the recent Polarix trial was that by introducing this new pola medicine instead of the older Oncovin treatment, we’re able to lead to longer durations of remission for patients with newly diagnosed large cell lymphoma and is able to do so without any increase in short- or long-term side effects, which makes it a real win in my mind.  

That’s one major innovation. The second is in patients who, unfortunately, have a relapse of their diffuse large B-cell lymphoma or whose disease does not go into remission after first treatments. We now know that patients who have an early relapse or have, what we call, primary refractory disease, meaning it didn’t go away after the first treatment at all, is we now have data using treatments that are calling CAR-T cell, or chimeric antigen receptor modified T-cell therapy. CAR-T cell therapy is a treatment in which we use your own body’s healthy T cells. Some of those are filtered out, and they are genetically re-engineered in way that trains them to attack lymphoma cells and then given back as a living treatment, as a mini-transfusion.  

This CAR T-cell therapy was compared to a standard chemotherapy program that uses high dose therapy with stem-cell rescue or auto transplant, or stem cell transplants, for patients with this high-risk scenario, early relapse or primary refractory disease. 

And what we found is that CAR T-cell therapy with either the treatment called axi-cel (Yescarta) or the treatment called liso-cel (Breyanzi),two different CAR-T therapies, were superior to the traditional chemotherapy and stem-cell transplant approach in these highest risk patients leading to marked improvements in outcomes in these patients and maybe even improving overall survival, which is a very high benchmark at this early time point in these two critical trials. So, improvements in newly diagnosed therapy and improvements for those patients who suffer early relapse or primary refractory disease mark two important advances in the care of patients with DLBCL.  

Katherine Banwell:

What are you excited about when it comes to DLBCL treatment and research?  

Dr. Matasar:

What I’m most excited about is our ability to improve outcomes in the highest risk patients. We often talk in academic circles about unmet need, which is just a silly way of saying we really wish we could do better. And there’s unmet need across the line when we think about how we take care of patients with aggressive B-cell lymphoma, newly diagnosed patients, patients who are newly diagnosed who may be older or more frail, who may need specialized treatment approaches, patients who suffer a relapse of this disease one or multiple times.  

We cure many patients with diffuse large B-cell lymphoma, but many is not enough. And we’re not going to rest until we can have uniform and universal success and, unfortunately, we’re not there. But we’re working to get there day after day. The options are expanding. The trials are promising. Novel therapies are very exciting, and I really believe that these next years are going to see profound innovation and improvements in outcomes. That comes with clinical research and with patients being willing to trust doctors to participate in this journey together and doctors being willing to take a chance and offer patients novel therapies when we know that our current treatments are simply inadequate. 

What Should Patients Know About DLBCL Treatment and Research?

What Should Patients Know About DLBCL Treatment and Research? from Patient Empowerment Network on Vimeo.

Why should diffuse large B-cell lymphoma (DLBCL) patients feel empowered to participate in their treatment and care decisions? Dr. Kami Maddocks reviews current DLBCL therapies, discusses developing research in the field, and shares advice encouraging patients to speak up and become active members of their team.

Dr. Kami Maddocks is a hematologist who specializes in treating patients with B-cell malignancies at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Maddocks, here.

Download Guide

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Transcript:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we are going to talk about diffuse large B-cell lymphoma, known as DLBCL and how you can feel empowered to speak up and be a partner 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 health care team about what might be best for you. Well, joining us today is Dr. Kami Maddocks. Dr. Maddocks, welcome. Would you please introduce yourself?

Dr. Maddocks:

Thank you. I’m Kami Maddocks. I’m a lymphoma doctor at the Ohio State University James Comprehensive Cancer Program.

Katherine:

Excellent. Thank you so much for being with us today.

Dr. Maddocks:

Thank you for having me.

Katherine:

Well, since the goal of this webinar is to help our viewers feel empowered in their care, in your opinion, what does it mean to be an empowered patient?

Dr. Maddocks:

I think an empowered patient is invested in their health and in their medical care. This can look like different things for different patients but I think being educated about their disease, being invested in decision making, along with their providers, and then being invested in the outcomes of their treatment and their disease.

Katherine:

What do you feel is the patient’s role in their care?

Dr. Maddocks:

I think it’s important that the patient partners with their care providers and their family, while they’re going through treatment for any condition. So, I think the most important thing is that the patient is comfortable with their care. And I think that includes being educated on their disease process. For some patients, this is going to be doing some of their own research, for some patients, this is going to be really relying and trusting in what their physician and care provider say, and for some patients, this is going to include other information that they seek out after they get the information from their care provider.

Katherine:

How do you empower patients?

Dr. Maddocks:

When I first meet a patient, I schedule a large block of time to spend with the patient, and I like to explain to the patient their new diagnosis. Or, if it’s not a new diagnosis, what I know about their disease, try to understand if they understand what I’m explaining, and what they know before coming to see me.

If there are treatment options, discuss those and go over those and make sure that I ask them to repeat or go over what they understand, from what I’ve explained from that. And then, making sure that they’re comfortable with available options outside of that. So, are there clinical trials available? Should they be seeking second opinions? Where is it best for them to get those second opinions? And then, ensuring that we have open lines of communications, so they have ways to contact me or my office. Making sure that they’re comfortable following up with questions that come in throughout the disease treatment and process. Ensuring that they know to contact us if there are changes or concerns so that we can address things in real time.

Katherine:

Yeah. That’s great advice, Dr. Maddocks. Thank you. Now, let’s learn more about DLBCL. For those who may be newly diagnosed, what is it?

Dr. Maddocks:

Diffuse large B-cell lymphoma is a type of non-Hodgkin’s lymphoma. So, this is considered a blood cancer. Lymphomas are a cancer of the lymphocyte, which is one of the types of blood cells that form your immune system. So, when you think about your nodes, these are part of the cells that help fight different types of infection. So, diffuse large B-cell lymphoma is one of the types of non-Hodgkin’s lymphomas, it’s aggressive, and it is considered an aggressive form of lymphoma. And it’s when you get a cancer of those lymph cells that often involved the lymph nodes but could also involve bone marrow, blood cells, other sites outside of the lymph nodes.

Katherine:

Do we know what causes DLBCL?

Dr. Maddocks:

For the most part, we don’t know what causes diffuse large B-cell lymphoma. So, most of the time, it’s going to arise with patients not having risk factors. We know that age is the most common risk factor with the median diagnosis of a patient in their 60s.

Although, we also know that diffuse large B-cell lymphoma, why it’s more common to be diagnosed later in life, can occur across all the age spectrum. So, you see this in pediatric adolescents, young adults, and older adults. There are some causes. These represent more than minority of cases but certain viruses, including HIV virus, can be associated with the development of lymphoma. Certain other medical conditions, like rheumatologic conditions and some of the treatments for these, can be associated, and then, some chemical exposures. But in general, most of the time, we’re not going to have an identified cause.

Katherine:

What are the symptoms?

Dr. Maddocks:

They can look a little bit different for different patients. So, because this is often a cancer, most of the time there will be lymph node involvement. For some patients, they can actually feel or somebody will see a lymph node that grows. Most of the time, when this occurs, it’s going to be in the neck, under the armpits, or in the groin area.

Patients can start to have symptoms from other sites, of those lymph nodes growing or disease so that they can get pain or shortness of breath. Or they can have what’s called B symptoms. So, B symptoms are inflammatory like symptoms from the lymphoma, and these include weight loss. So, a rapid change in weight for no reason. Night sweats. So, daily night sweats, we call them drenching night sweats. They wake up the patient, they soak their clothes, sometimes they soak the whole bed. And then, fatigue. So, extreme fatigue, not able to do your daily activities. And then, occasional people will have cyclical fevers.

Katherine:

Are there different types of DLBCL?

Dr. Maddocks:

So, in general, diffuse large B-cell lymphoma, there’s one major subtype. You can divide it into different pathological or molecular subtypes.

So, where the cell develops lymphoma during the cell’s development, there are different chromosome abnormalities. So, there are different categorizations but in general, diffuse large B-cell lymphoma itself is considered – it’s treated, often, the same even with these different subtypes. So, there are different subtypes but in general, they’re all considered a form of diffuse large B-cell lymphoma.

Katherine:

They’re under this umbrella of DLBCL.

Dr. Maddocks:

Yeah. Yeah.

Katherine:

Yeah. Do patients usually get diagnosed after they experience some symptoms?

Dr. Maddocks:

So, because this is an aggressive lymphoma, there are a lot of patients that will have symptoms with this, and that’s how they’ll present. Via either noticing the lymph nodes, having the B symptoms, or having pain, or other abnormalities from the lymphoma progressing.

Occasionally, whereas indolent lymphoma is more commonly found of incidentally. Occasionally, that’ll be the case with these, but I would say a fair number of patients have some sort of symptom or something that brings them to medical attention.

Katherine:

How does DLBCL progress?

Dr. Maddocks:

So, they’re different, as far as there’s more aggressive and less aggressive. So, some patients can develop symptoms, really, over days to weeks. Whereas, some patients are more weeks to months.

Katherine:

“Okay. Let’s turn to treatment options. Is a person with DLBCL treated right away?”

Dr. Maddocks:

They’re treated pretty quickly after the diagnosis. So, typically, when somebody has a diagnosis, they undergo a number of different tests, including lab work, imaging work, sometimes for their biopsies.

So, that information is gathered over days to sometimes a few weeks process. Then, when you have all that information, you go over the results, go over the treatment at that time. So, it’s typically treated not within, usually, a day of diagnosis but it’s not something that you spend weeks or months before treating.

Katherine:

Yeah. What are the different types of treatments available?

Dr. Maddocks:

So, the diffuse large B-cell lymphoma is treated with chemotherapy and immunotherapy. So, a combination of an immune antibody therapy and chemotherapy. There is a role in some cases for radiation, but never just radiation alone and never just surgery alone. So, there’s always what we call a systemic treatment. So, a treatment that goes everywhere. Because this is considered a blood cancer, it’s a cancer of those cells, it can really spread anywhere.

And so, just cutting it out with surgery or just radiating the area doesn’t treat everything, even if you can’t identify it.

Katherine:

Can you get specific about some of the treatment classes?

Dr. Maddocks:

Yeah. So, the most common treatment for diffuse large B-cell lymphoma is a chemo immunotherapy called R-CHOP. So, this is three chemotherapies and antibody therapy that’s direct called rituximab (Rituxan) that’s directed at a protein on the lymphoma cells. And then, a steroid called prednisone, given with the chemo and then for a few days after. There was a study that recently showed an improvement with switching one of those drugs with another immunotherapy that’s an antibody conjugated to a chemo drug. But that’s not yet been approved. There are clinical trials available. So, looking at these treatments that might be new or combining therapies with this standard treatment.

And then, very occasionally, there are certain features of diffuse large B-cell lymphoma. There are particular few different subtypes that are classified a little bit differently, that are treated within an infusional therapy called Dose Adjusted R-EPOCH.

Katherine:

What about stem cell therapy? Is that used?

Dr. Maddocks:

Stem cell therapy is used in the relapse setting. So, if a patient doesn’t go into a remission or if they relapse after achieving a remission with their chemotherapy, then stem cell transplant is an option. So, there are actually two different types of stem cell transplant. One from yourself and one from somebody else. In lymphoma, we typically do one from yourself, where you donate your own cell before. But we don’t use that as part of the initial treatment.

Katherine:

So, if somebody is high risk, Dr. Maddocks, is the approach different for them?

Dr. Maddocks:

So, it depends. We define high risk in different ways. So, there’s a specific type of lymphoma called double hit lymphoma, where there’s a few chromosomal translocations associated with the lymphoma, that we give a little more aggressive chemo immunotherapy regimen. There are also other subtypes, including a rare type of lymphoma called primary mediastinal B-cell lymphoma. Again, categorized a little bit different but sometimes included as a large cell lymphoma. We also give that treatment for.

Katherine:

Is a cure possible?

Dr. Maddocks:

Yes. A cure is possible. When you look at patients who are treated with initial chemotherapy, we cure somewhere between 60 percent to 70 percent of patients with the initial chemotherapy. If patients’ relapse, depending on their age and their condition, they’re candidates for other therapies.

And therapy including other chemo and stem cell transplant is potentially curable in some patients. And then, there’s a newer therapy called chimeric antigen receptor T-cell, or CAR T-cell therapy, which also looks like it’s curing a subset of patients who relapse or don’t respond to initial therapy.

Katherine:

Okay. What are the side effects that patients can expect with these treatments?

Dr. Maddocks:

So, when they get the treatment, on the day they get it, there can be an infusion reaction to the rituximab or antibody therapies. So, the first treatment, that treatment is given very slowly and titrated up. If patients have a reaction, we stop it, treat the reaction, and then they’re able to continue therapy but again, that first day, it can take several hours for that one antibody to get in. And then, later, therapies are given at a more rapid pace.

So, about 70 percent of people who react, it can be really almost anything. Some people get flushing, some people will get a fever, some people have shortness of breath or their heart rate will go up.

Katherine:

Okay. All right. Any other side effects?

Dr. Maddocks:

Yeah. So then chemotherapy is meant to kill cells during the cell cycle. So, cancer cells divide more rapidly, chemotherapy is targeting them, but it also effects good cells in the body, specifically those that divide at a more rapid pace. The biggest risk of chemotherapy is infection.

So, it effects the good white blood cells that fight infections. It can affect your red cells that carry your iron, gives you your energy. Or your platelets which help you to clot or not bleed when you get caught. So, infection is the biggest risk of chemotherapy. So, usually, with this regimen, that infectious risk is highest within the second week of treatment, that treatment is given every three weeks.

So, we tell patients they should buy a thermometer, check their temperature, they have to notify their doctor or go to the ER if they have a fever. Besides infection, there’s a small percentage of patients who might need a transfusion. GI toxicity. So, nausea, vomiting, diarrhea, mouth sores, constipation, all of which we have good treatments for. So, we give medication before chemo to try to prevent people from getting sick and then give them medicine to go home with, if they have any nausea. We can alter those medications as time goes on, if they’re having any problems. So, we just need to know about it. Most patients will lose their hair with this regimen.

It can affect people’s tastes, it can make their skin more sensitive to the sun, and then, less common but potential side effects are it can cause damage to the nerves. Or something we call neuropathy, which most often patients will start with getting numbness or tingling in their fingers and toes, and we can dose adjust if that’s causing some problems.

And then, there’s a risk to the heart with one of the drugs. So, the heart should pump like this. The heart pump function can go down. So, we always check a patient’s heart pump function before they get their chemo, to make sure that they’re not at higher risk for that to happen.

Katherine:

So, all of these approaches are used in initial treatment?

Dr. Maddocks:

Mm-hmm.

Katherine:

Okay. So, how do you know if a treatment is working?

Dr. Maddocks:

So, as far as evaluating treatment, you get a scan before you start treatments, so we know where all the lymphoma is at. And then, typically, you get some sort of scan in the middle of treatment, and then after, you complete your six cycles of treatment. Or for early stages, sometimes patients will get less than six cycles. So, we get scans to make sure it’s working. So, you can tell by those things, how much has gone, hopefully all of it has gone by the end. Occasionally, patients that had a lot of symptoms to start with, their symptoms will go away, and then they’ll start coming back.

This is less common, because the majority of patients do respond to chemotherapy. It’s less common to get patients who are what is called refractory, meaning they don’t get any response to therapy. So, occasionally they’ll note symptoms but a lot of times, we’ll see something on that mid-therapy or end of therapy scan, if it’s not going to make it all go away.

Katherine:

Yeah. So, if a treatment doesn’t work, what happens then?

Dr. Maddocks:

If treatment doesn’t work, it depends a little bit – and now it depends a little bit on the timing of that treatment not working. So, it used to be that patients who were eligible for treatment, no matter if it didn’t work right away or if it put them into what we call a remission, so there’s no evidence of disease and then it relapsed, they would have the option of further chemotherapy and then an autologous stem cell transplant. So, a bone marrow transplant where they donate their own cells.

If they were in a good enough health or if they were not – to do that, you have to donate your own bone marrow cells and as we age, we make less bone marrow cells. So, once you reach a certain age, your body can’t produce enough cells to donate to a transplant. In those patients, we offer them less aggressive chemo options, which were not known to be curable but could put them into remission again, for a while. More recently, there has been some that chimeric antigen receptor T-cell therapy that I mentioned where you actually donate your own T cells. So that’s –And your lymphoma is of your B cells.

Your T cells are in another immune cell that should recognize that lymphoma is bad and attack it, and they’re not functioning properly. So, you donate your own T cells and they’re sent off and reengineered to target a protein on the tumor. Then, you get those cells back and they’re meant to target the lymphoma and kill the lymphoma cells.

So, that is now an approved therapy for patients who don’t achieve the remission – so, who’s first chemo doesn’t work or if they relapse within a year of completing chemo. So, that’s a possibility. The chemo and transplants a possibility. Or there’s other approved therapies now, that can be given as second options or third or later options, which have been shown to keep patients in remission for a while.

Katherine:

Dr. Maddocks, you touched up on this a moment ago but what are the approaches if a patient relapses? What do you do?

Dr. Maddocks:

So, you would rework them up if they relapsed. Similar to that, if they relapse within a year and they have access to the CAR-T and they’re healthy for that, then that’ll be an option. The second type of chemotherapy in the transplant. So, you can’t just go straight to a transplant. You have to get a different type of chemotherapy to try to get the disease under control again, before you would go to a transplant.

Or there’s a number of other targeted therapies that are approved. So, there’s other – I talked about rituximab is given in the first line, that targets a CD-20 protein, there’s an antibody that targets a CD-19 protein that’s given out in relapse. There’s another antibody drug – there’s actually two antibody drug conjugates. So, an antibody that targets the protein on the cells that are attached to a chemo, that’s given. Or there’s different chemotherapy and then even some oral therapies.

Katherine:

Okay. So, there’s a lot of different options available for people.

Dr. Maddocks:

Correct. And there’s always clinical trials. So, there’s always the option to find something where we’re studying some of these newer therapies. They’re therapies in combination.

Katherine:

Well, that leads us right into emerging options and I’d like to talk about that. Have there been any recent developments in how DLBCL is treated?

Dr. Maddocks:

There had been recent developments. So, the CAR T-cell therapy, there is now three approved options for patients. And so, even patients who maybe are older and not considered candidates for a stem cell transplant because of other medical factors, might be able to get the CAR T-cell therapy. This is now, again, approved in the second line. There are a couple antibody drug conjugates, polatuzumab (Polivy) and loncastuximab (Lonca, Zylonta), they target proteins called CD-79 and CD-19.

And the polatuzumab’s the one that probably is going to be available for part of the front-line treatment in the future. There’s the antibody tafasitamab (Monjuvi) and lenalidomide (Revlimid). These are all approved therapies in the relapse setting. There are also therapies that are being studied and showing promising activity, which we think are probably likely to be approved in the future. There’s something particularly called bi-specific antibodies.

So, this targets a protein on the tumor cell but also a protein on the T cell. So, remember I said the T cells aren’t functioning. So, this targets the protein on the lymphoma cell but then targets a protein on the T cell to engage it to attack the lymphoma cell.

Katherine:

Right. Combination approaches?

Dr. Maddocks:

Yeah. So, there are a number of combination approaches under study a lot of the therapies that I mentioned, like the bi-specific antibodies, the antibody drug conjugates. These are all therapies that – they have side effects – I hate to say they’re well-tolerated – they have side effects but their side effects are such that they can be combined with other agents, that have different toxicities that are combined with each other. And so, there’s a lot of ongoing trials looking at combining these. There’re also oral targeted therapies that target proteins that are known to help the lymphoma cells survive and these are modulator therapies, BTK inhibitors, other inhibitors, that are being evaluated and used in combinations.

Katherine:

Thanks, Dr. Maddocks. That’s really helpful information. So, now that we understand more about DLBCL and how it’s treated, let’s talk about self-advocacy and how patients can engage in their own care. Why is it so important for patients to have a voice in their decisions?

Dr. Maddocks:

Well, I always tell my patients that they are the person most invested in their selves and their outcomes. As a care team, we certainly are invested in them and we want them to do well but they’re the one that knows their body, they know what’s going on, they’re the one that has to, essentially, live with all these outcomes. So, they have to be invested in what’s going on, they have to be invested in making sure that they know their care team is informed of things because we only see them in different periods of time and we’re not with them all the time to know what’s going on.

Katherine:

Right. It’s not always easy for patients to speak up. So, I’d like to debunk some common misconceptions that patients have, that may be holding them back. First one is, “I’m bothering my doctor with all my questions.” Is that true?

Dr. Maddocks:

That is not true at all. So, the best thing is an informed patient. So, I want to answer all their questions. “What is the disease or diagnosis?” “What are the treatment options?” “What do we know now?” “What are we learning?” I need to know what’s going on. I always tell my patients that I can’t help them with what I don’t know. So, if somebody shows up, they get once cycle of treatment and they show up for a second cycle and they’ve had all these problems and never called or notified me, first of all, we weren’t able to help them. There’s a lot of things we can do to help them and if we don’t know what’s going on, we can’t help.

And second, that might impact that second treatment, whereas knowing and knowing that sooner, we can plan to make changes.

Katherine:

Yeah. That’s really good advice. Here’s another one. “My doctor’s feelings will get hurt if I get a second opinion.”

Dr. Maddocks:

Not at all. So, I always encourage patients that they should get a second opinion, third opinion, whatever they need. Number one, I think it’s important that a patient feels comfortable with their diagnosis and their treatment

plan because I really think that things go better if they understand that and they’re comfortable. If they’re always doubting what’s going on, it’s really hard to develop that trusting relationship. And I think it’s very important that a patient has a trusting relationship with their care team.

I think most of the time, when you get a second opinion, you’re probably going to hear or get the same advice. And so, that helps a patient to feel comfortable. Sometimes, there may be clinical trials out there that your doctor didn’t know about, that are options, and a doctor’s always going to be happy if there’s something out there available, that might make the patient outcome better, that they didn’t know about.

And lastly, I would say there are a lot of doctors who treat all types of cancer and there are some doctors that specialize in certain types of cancer. And so, if you were seeing a doctor who treats multiple different kinds, but want to see a doctor who specializes in a particular kind, they may be aware of a recent trial or a recent development that your doctor doesn’t know. Not because there’s anything wrong with that doctor, it’s just that there is so much data to keep up with these days, in cancer, that a specialist might be able to provide a point of view that somebody else doesn’t know.

Katherine:

Yeah. Another question or comment is, “There isn’t anything that could be done about my symptoms or treatment side effects. So, why should I even say anything?”

Dr. Maddocks:

That’s a great question but the thing is, a lot of times there are things. So, the one thing is, some of the treatments we use for some of our cancers, including lymphoma, have been around for a really long time. But some of the things that have changed, are our supportive care or our ability to treat patient side effects. So, I think that it’s always important that patients let us know if they’re having side effects because maybe nausea – so, we give medication to prevent that.

Usually, I send patients home with two different types of nausea medication. But if that’s not helping, I have more than two in my toolbox, I just don’t know to prescribe them if the typical things aren’t helping. So, a lot of times, there are things that we can do. Sometimes you have to tweak the dosing of the chemo, but really, the only way you can help with symptom management is if you know somebody’s having symptoms.

Katherine:

Right. So, when somebody starts to have side effects from the treatment, should they contact their care team right away?

Dr. Maddocks:

Yes. They should contact their care team right away. There are certain side effects, like having a fever during chemo, where they really need to go to the emergency room to be evaluated, to make sure it’s nothing. Because an infection can be very serious when you’re getting chemotherapy. Other side effects that are less emergent but, yes. Most of the time there’s a patient number that patients can call, where they can seek, like a nurse help line, where they can seek assistance, and that call can be escalated depending on the symptoms and what needs to be helped.

But I think, again, it’s important that we know what’s going on so we can help patients. And then, if something needs to be further investigated – because occasionally there will be something that’ll make us think, “Oh, we really need to evaluate this patient because what if it’s more than what it seems?”

Katherine:

Right. Are there any other misconceptions that you hear about from patients?

Dr. Maddocks:

I think, just in general, thinking about the patient taking care of themselves. So, a lot of times there can be resources that patients have questions on. Things like exercise. Things like nutrition. Things in the environment that they can be exposed to. Just different things. I think it’s always important that you ask your care team if there’s any question because they’re going to best be able to tell you versus just assuming something.

There’s a lot of good information that patients can get from educational sites. There’s a lot of good information on the internet but there’s also a lot of bad information, or inaccurate information on the internet. So, I think it’s great for patients to use resources and educate themselves but I think that it’s always good to confirm with your care team. Myths versus facts.

Katherine:

Yeah. Yeah. That’s really important. Do you recommend that patients continue getting vaccines? For COVID, for flu?

Dr. Maddocks:

Yes. So, particularly, when you look at lymphomas, this is a cancer of the immune system. The cancer can make your immune system compromise the treatment. While you’re getting treated makes your immune system compromised. And even for a period after treatment, your immune system can be compromised. So, it’s important to protect yourselves against infection. Sometimes the efficacy of vaccines in the middle of treatment might not be as good as not being on treatment.

But that said, there’s no data that the vaccines are harmful. You do have to be careful about live vaccines when you’re under treatment, and you should ask your doctor about not the typical vaccines, of course. But I think that it’s very important to take every step that patients can, to try to prevent themselves from battling something in addition to them already undergoing treatments, their body’s already going through a lot.

And so, anything that we can do or they can do to help prevent them from dealing with more than they already are, I think is important.

Katherine:

To close, what would you like to leave the audience with? Do you think that people can feel hopeful about the tools available to treat DLBCL?

Dr. Maddocks:

Yeah. I think, if you look at the progress we’ve made in the last five years, the last drug approved was rituximab in the early 2000s, and now in the last five years, we have had numerous therapies approved. Now it looks like we’re changing front-line therapy and numerous therapies that relapse. So, there’s a lot of – these are all promising therapies, some of them potentially curing patients that we weren’t able to cure before.

And so, they’re more available to patients. There’s a lot of promising drugs in clinical trials. And so, I think it’s hard to deal with a diagnosis but there are options for patients, both initially and at relapse, and I think seeking out what’s available, both to you and in clinical trials, is important to helping further improve outcomes.

Katherine:

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

Dr. Maddocks:

Thank you so much. It’s been a pleasure.

Katherine:

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

Tips for Managing Your Oral CLL Treatment Schedule

Tips for Managing Your Oral CLL Treatment Schedule from Patient Empowerment Network on Vimeo.

Patients taking an oral CLL therapy have a responsibility in managing their own care. Dr. Jean Koff, a CLL expert from Winship Cancer Institute of Emory University, discusses the importance of staying on schedule with medications and shares advice for being consistent.

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.

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Transcript:

Katherine Banwell:

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.   

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.  

Can a CLL Patient’s Response to the COVID Vaccine Be Boosted?

Can a CLL Patient’s Response to the COVID Vaccine Be Boosted? from Patient Empowerment Network on Vimeo.

Is there a way to boost COVID vaccine response in patients with CLL? Dr. Jean Koff explains ongoing progress being made to protect CLL patients from COVID.

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.

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Transcript:

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 (Venclexta), 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 12 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 tixagevimab co-packaged with cilgavimab (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.  

What is YOUR Role in Choosing a CLL Treatment Approach?

What Is YOUR Role in Choosing a CLL Treatment Approach? from Patient Empowerment Network on Vimeo.

Dr. Jean Koff shares her perspective on the role of patient when deciding on a CLL treatment approach and reviews key factors that should be considered.

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.

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Transcript:

Katherine Banwell:

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 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 (Imbruvica), 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 r egimen, 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.  

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.

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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.  

What Are the Current CLL Treatment Options?

What Are the Current CLL Treatment Options? from Patient Empowerment Network on Vimeo.

When is it time to treat CLL, and what are the current options? Dr. Jean Koff, from the Winship Cancer Institute of Emory University, reviews available CLL treatment approaches and discusses patient-specific factors that she considers when choosing therapy.

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.

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Transcript:

Katherine Banwell:

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 (Imbruvica), 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  (Calquence), and that is often given with an IV monoclonal antibody called obinutuzumab (Gazyva).   

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 (Venclexta). 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 combination – 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.