Tag Archive for: Rituxan

How Is Relapsed or Transformed Follicular Lymphoma Treated?

How Is Relapsed or Transformed Follicular Lymphoma Treated? from Patient Empowerment Network on Vimeo.

Follicular lymphoma (FL) expert Dr. Jane Winter explains relapsed or transformed follicular lymphoma and outlines treatment approaches for these FL types.

Dr. Jane Winter is a hematologist and medical oncologist at Robert H. Lurie Comprehensive Cancer Center at Northwestern University. More information on Dr. Winter here.

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Transcript:

Laura Beth:

Dr. Winter, what happens if a patient’s follicular lymphoma relapses? What is the approach to treatment? 

Dr. Winter:

And so, generally, it’s probably one in five patients whose disease sort of comes back and becomes somewhat problematic requiring repeated therapies where many, many patients have a very kind of indolent course that may require treatment intermittently, but tends to be very amenable to treatment. And then the other point to be made about follicular lymphoma is indeed that a fraction of patients every year will go on to what we call transform. That means their disease acquires and changes biologically or at least a clone of their disease changes and becomes a much more aggressive process similar to a newly diagnosed diffuse large B-cell lymphoma, an aggressive lymphoma.  

And these transformations then require treatment as if they were an aggressive lymphoma. And they also, despite being somewhat frightening because of the sense of changing from a low-grade to a more aggressive process, in very many cases, these are well treated with standard, especially in patients who haven’t had prior therapy for follicular lymphoma, which is rituximab (Rituxan), these patients are well treated with our standard treatment for aggressive lymphoma Rituxan CHOP chemotherapy, and do very well. So, even though that sounds like a frightening occurrence, for the vast majority, it’s very treatable. 

And patients go into remission and stay in remission for the most part, so it’s not as frightening as it might sound. And how many patients and when do they transform? There’s lots of confusing data. Basically, there’s some data that suggests that the majority of patients transform early in the first five years, whereas other data suggests that it’s sort of every year, patients are at risk so that the longer you have follicular lymphoma, perhaps, the greater the risk overall of this kind of change in the biology. But, as I said, for a good significant number of patients, this is relatively easily treated with standard chemotherapy.   

Just another point in terms of potentially curative therapies these days, we’re afraid to use that term in follicular lymphoma because it does have this tendency to sort of keep coming back over time. So, whether any treatment is truly curative remains to be seen. Perhaps a very, very small fraction of patients might be eligible, young patients, for an allogeneic stem cell transplant from someone else. But, this is not commonly pursued these days, as well as a new therapy called CAR T-cell therapy, which is a form of immunotherapy and may indeed be curative.  

But at this point, it’s really too early to make a claim of cure with that strategy. But, a very exciting new immunotherapy as well as some other new immunotherapy is something called “bite cells,” which harness our own immune system, much like the CAR-T cells do. So, lots of new things. So, these are exciting times for us as treating physicians and hematologists, but they are exciting times for patients because we have so much to offer.  

An Expert’s Perspective on Emerging Follicular Lymphoma Research

An Expert’s Perspective on Emerging Follicular Lymphoma Research from Patient Empowerment Network on Vimeo.

What’s the latest on emerging follicular lymphoma research? Dr. Jane Winter shares how follicular lymphoma treatment has advanced and provides an overview of treatment options.

Dr. Jane Winter is a hematologist and medical oncologist at Robert H. Lurie Comprehensive Cancer Center at Northwestern University. More information on Dr. Winter here.

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Follicular Lymphoma: What Treatment Options Are Available?


Transcript:

Laura Beth:

Dr. Winter, is there emerging follicular lymphoma research that you are excited about?   

Dr. Winter:

So, first of all, I think it’s very important to underscore the fact that for a newly diagnosed patient with follicular lymphoma today, survival is measured in decades with an “S,” so, 10, 20-plus years. And that’s based on data that’s already becoming outdated such that it’s the likelihood with some of the newer treatment options is there’s never been a more exciting time, I often say, to be a hematologist because of all the exciting new tools we have to our trade.  

So, lots of new treatments. But, even with the old treatments, and I mean rituximab-based treatments, the outcome is excellent. We have new treatments. We have all kinds of new treatments these days for follicular lymphoma such that it’s a veritable buffet of treatment options to choose from. Nonetheless, often times the first treatment is just either a monoclonal antibody, meaning rituximab, an anti-CD20, which is a protein or marker on the surface of the lymphoma cell. This is immunotherapy, been around now for 30 years and approved for 22 years for the treatment of follicular lymphoma as well as other B-cell lymphomas.  

Other therapies that are typically used frontline include rituximab plus chemotherapy, most commonly a drug called bendamustine, which wasn’t always available, was something that was being developed in East Germany that came to the attention of the Europeans and North Americans only after German unification. And, this has become, along with Rituxan, one of the most commonly used first-line treatments for follicular lymphoma. Other options include a combination of Rituxan and an oral medication called lenalidomide (Revlimid), and this is given three weeks in a row out of every four weeks with Rituxan. Again, this anti-CD20 immunotherapy or antibody. 

And, it’s a very effective but requires some monitoring of blood counts and so on, so it is perhaps not as commonly used as Rituxan and bendamustine as a first-line therapy. But, there are so many additional new options that are either approved or coming along for all of our B-cell lymphomas, and they include many new what we call “targeted agents” as well as immunotherapy including a very new therapy called CAR T-cell therapy. But, one thing I just wanted to say, in addition to the very long anticipated survival of newly diagnosed patients today, it’s really only a small fraction of patients who get into trouble with follicular lymphoma, at least in the short term.  

What Do You Need to Know About Follicular Lymphoma?

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

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

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Transcript:

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

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

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

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

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

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

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

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

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

When it is time to treat, options may include: 

  • Radiation therapy 
  • Chemotherapy 
  • Targeted therapy 
  • Immunotherapy 
  • Or cellular therapy, such as CAR T-cell therapy or a bone marrow transplant. 

Your physician may also recommend clinical trial options. 

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

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

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

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.

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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.

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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.

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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.

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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.  

What Are Common Side Effects of DLBCL Treatment?

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

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

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

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Transcript:

Katherine Banwell:

What are common side effects of DLBCL treatment approaches? 

Dr. Matasar:

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

And hair loss is unavoidable with these treatments although temporary.   

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

What Do 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.

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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.

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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.

Which Emerging DLBCL Therapies Are Showing Promise?

Which Emerging DLBCL Therapies Are Showing Promise? from Patient Empowerment Network on Vimeo.

What’s next in diffuse large B-cell lymphoma (DLBCL) treatment? Dr. Justin Kline reviews developing research that could transform the future of DLBCL treatment.

Dr. Justin Kline is the Director of the Lymphoma Program at the University of Chicago Medicine. Learn more about Dr. Kline, here.

See More From The Pro-Active DLBCL Patient Toolkit

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Which Factors Impact DLBCL Treatment Decisions?

Which Factors Impact DLBCL Treatment Decisions?

How Is Diffuse Large B-Cell Lymphoma (DLBCL) Treated?

How Can Patients Access the Latest DLBCL Treatment Options?


Transcript:

Katherine:      

What about emerging therapies, Dr. Kline? What approaches are showing promise?

Dr. Kline:       

Well, I think probably in DLBCL, the biggest breakthrough, I don’t even know that I can call it emerging at this point, because it’s on the market, so to speak.

But I think it’s important to talk about, again, is CAR T-cell therapy, and this is a type of immune therapy where a person’s own immune cells called T-cells are taken from his or her bloodstream. And then using a special type of a virus, those T-cells are manipulated or engineered, that sounds better, to express on their surface something called a chimeric antigen receptor, which is somewhere between an antibody and a normal T-cell receptor. But anyhow, this chimeric antigen receptor confers or allows the T-cell to recognize a protein that’s expressed on the surface of B-cells, cancerous or otherwise, called CD19. And when that chimeric antigen or CAR antigen, excuse me, that CAR receptor expressing T-cell sees a lymphoma cell, it engages it and kills it, a pretty clever idea which has been in the works for decades now.

But CAR T-cell therapy has now been approved for not only DLBCL but many other types of non-Hodgkin lymphoma. And I think in the past decade, far and away, that’s the biggest breakthrough. There are other types of immunotherapy, probably most notably a type called bispecific immunotherapy, which is a pretty clever type of immune therapy where these specially engineered antibodies that are capable of binding or sticking to not only a person’s T-cell, a T-cell that’s already in his or her body, and a B-cell, a lymphoma cell that’s right next to that T-cell, sort of holds them together, and the part that binds the T-cell actually activates it, triggers it to kill the B-cell. And so there are a number of companies that have those bispecific therapies that are in development. I suspect a couple will be approved by the FDA, I would guess, in 2022.

These bispecific immunotherapies have been very effective, again, in DLBCL that’s come back, relapsed or refractory, as well as in other lymphomas. They do have some side effects that are similar to what we see in folks with CAR T-cell therapy. I won’t belabor what those are, but they are also very effective. There’ve been a number of drugs that, either immunotherapies or other types of therapies, that target that same CD19 protein on diffuse large B-cell lymphoma cells that have recently been approved by the FDA, either alone or in combination. Targeted therapies are always exciting. Although as compared with other lymphomas, these targeted therapies, many of which are oral, which are pills, have not been particularly effective in relapsed DLBCL.

So, I think that among the most exciting therapies are those that take advantage of our own immune systems to recognize and kill the lymphoma cells.

How Is Relapsed/Refractory DLBCL Treated?

How Is Relapsed/Refractory DLBCL Treated? from Patient Empowerment Network on Vimeo.

What options are available if a diffuse large B-cell lymphoma (DLBCL) patient doesn’t respond to treatment or relapses? Dr. Justin Kline discusses potential next steps in treatment for DLBCL patients with relapsed or refractory disease. 

Dr. Justin Kline is the Director of the Lymphoma Program at the University of Chicago Medicine. Learn more about Dr. Kline, here.

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Transcript:

Katherine:      

Let’s talk about if someone doesn’t respond to initial treatment or they relapse. Let’s start by defining some terms for the audience. What does it mean to be refractory?

Dr. Kline:       

So, refractory is a term that’s used to describe a situation where a person has received treatment but that treatment hasn’t worked as well as we have expected. And the most – probably the most important scenario is after initial treatment.

Most people, for example, who receive R-CHOP, somewhere between 80 and 85 percent will have a completely negative PET scan after treatment. That’s remission. If the PET scan is not negative and you do a biopsy and it shows that there’s still lymphoma there, that’s what’s called primary refractory. In other words, the person’s lymphoma was refractory to initial or primary treatment. And in clinical trials that are testing agents, drugs or immunotherapies in folks who’ve had multiple treatments, usually refractory is used to define someone who has either not responded or has had a very, very short response to whatever the last treatment they had was.

Katherine:                  

How does relapse then differ from refractory?

Dr. Kline:       

So, right, so relapse suggests that the lymphoma at some point was in a remission, right?

And so for example, a person gets six treatments of R-CHOP, has a PET scan at the end, the PET scan is clean. We say you’re in remission. Eight months later, the person develops a newly enlarged lymph node, and a biopsy shows that the lymphoma has come back, right? That’s what we would call a relapse. There was a period of remission, whereas refractory usually means there was never a period of remission to begin with.

Katherine:                  

Got it. How typical is it for a patient to relapse?

Dr. Kline:       

Well, again, if you look at all comers, if you treated 100 people with DLBCL, most, probably 70 to 75 percent, would go into remission. About 10 or 15 percent would have primary refractory disease and another 10 or 15 percent would have a remission that would end at some point and they would have a relapse. So, it’s not terribly common.

The problem is that once the lymphoma has either demonstrated that it’s refractory to treatment or it’s come back, it’s relapsed, it’s a little bit more difficult to cure the lymphoma at that point.

Katherine:      

How are patients treated then if they’ve relapsed or refractory?

Dr. Kline:       

Well, so for somebody who’s had primary refractory lymphoma or has a lymphoma that’s relapsed after initial therapy, again, say for the sake of argument with R-CHOP, for many, many years, the next line of treatment if you will was to administer what we call salvage chemotherapy, and this is different chemotherapy from the original R-CHOP, that’s meant to put the lymphoma back into remission. In other worse, to salvage a remission. And for folks whose lymphomas were sensitive or responded, shrunk down to that salvage chemotherapy, we would consolidate that remission.

We would make it deeper using high dose chemotherapy and an autologous or a cell, stem cell transplant. And that’s been the standard of care for younger patients for decades.

That paradigm has been challenged, particularly in refractory patients or those who have very early relapses after R-CHOP, by two important clinical trials that have demonstrated superiority of a type of immunotherapy, a cellular immunotherapy called CAR T-cell therapy, which seems to be more effective even than stem cell transplantation in that population of folks.

Which Factors Impact DLBCL Treatment Decisions?

Which Factors Impact DLBCL Treatment Decisions? from Patient Empowerment Network on Vimeo.

When making a decision about diffuse large B-cell lymphoma (DLBCL) treatment, what should you consider? Dr. Justin Kline reviews key patient factors that impact therapy decisions, including comorbidities and treatment side effects.

Dr. Justin Kline is the Director of the Lymphoma Program at the University of Chicago Medicine. Learn more about Dr. Kline, here.

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How Is Relapsed/Refractory DLBCL Treated?


Transcript:

Katherine:      

Other than a newly diagnosed patient’s stage of DLBCL and their age, what other factors would impact a treatment decision?

Dr. Kline:       

Yeah. So, that’s a good question, so you named I think the biggest two, the most important two. Although I have to say that even people in their – oftentimes in their 80s are prescribed full dose therapy. The goal of our treatment, especially in newly diagnosed patients, is to cure the lymphoma, and so we tend to be aggressive. But outside of age, other things we consider are other health problems. Does the person have a healthy heart, healthy kidneys? How many other medical problems does the person have? How fit is the person? How sick is the person or symptomatic is the person from his or her lymphoma? And sometimes we take into consideration all those factors and we say, well, it’s still worth it to try to deliver the most intensive therapy that we can.

Other times we say, you know what? I think the risk of doing such is probably not worth the potential benefit, and so sometimes we’ll recommend dose reductions, reduce the doses of some of the medicines and the R-CHOP cocktail if that’s what we’re going to do, and occasionally, if the person has too many other things going on, we may talk about more palliative treatments, in other words, gentler treatments that may extend a person’s survival while hopefully maintaining a really good quality of life.

Katherine:                 

Yeah. What kind of side effects should patients expect?

Dr. Kline:       

Well, that’s a conversation I’ve had many, many, many times over the years. And specifically to the R-CHOP cocktail, just because that’s the one that’s used most commonly, I tell people that the most common things are symptoms like fatigue, occasionally nausea, sometimes vomiting, although the medications we have to prevent those things are very good these days.

Constipation is not uncommon, hair loss, mouth sores. I think probably the most important thing is to recognize that the chemotherapy will suppress or reduce the immune system, and so we’re always worried about people catching infections when they’re on chemotherapy, because sometimes they can be serious. And then I talk about rare symptoms that are a big deal. Sometimes the chemotherapy can damage organs like the heart. It’s uncommon, but it happens sometimes. And chemotherapy, while we need to give it to cure the lymphoma, can sometimes cause secondary blood cancers like leukemias years down the road. The risk is low, but again, these are I think serious things that people, even if they’re rare, people need to know about them before they start.

How Is DLBCL Treated?

How Is Diffuse Large B-Cell Lymphoma (DLBCL) Treated? from Patient Empowerment Network on Vimeo.

Dr. Justin Kline explains what patients need to know about current DLBCL treatment, including R-CHOP, stem cell therapy, and clinical trials.

Dr. Justin Kline is the Director of the Lymphoma Program at the University of Chicago Medicine. Learn more about Dr. Kline, here.

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Transcript:

Katherine:      

From what I understand, treatment really should start right away. So, what types of treatment are currently available to someone newly diagnosed with DLBCL?

Dr. Kline:       

Sure, so for about 20 plus years now, the standard of care for most patients with DLBCL, regardless of whether it’s a germinal center or an activated B-cell type DLBCL, is a combination of what we call chemo immunotherapy, the acronym for which is R-CHOP, and each of those letters stands for a different medication. The R stands for rituximab, which is an antibody that coats the surface of lymphomatous B cells and sort of signals the immune system to come and kill those cells.

The C is cyclophosphamide, the H is hydroxy doxorubicin, and the O is Oncovin. These are each classical chemotherapy drugs, and they each work through a different mechanism to help kill lymphoma sells. And the P is a steroid pill called prednisone, so it’s a little bit complicated, but the reason that we use cocktails of medicines to treat lymphomas is that it really works to prevent the lymphoma cells from gaining the upper hand, from developing resistance to a single type of treatment.

Katherine:      

Right.

Dr. Kline:       

Now, I should say that for certain DLBCLs, particularly those double hit lymphomas that we talked about, sometimes we use a more intensive cocktail called dose-adjusted R-EPOCH. It has largely the same medications with an additional chemotherapy called etoposide.

The difference is that R-CHOP is given – all the drugs are given intravenously, with the exception of prednisone, over a single day. The dose-adjusted R-EPOCH is given over an infusion over the course of about five days. The other point I might make is that there was a recent large clinical study that compared R-CHOP to a new regimen called polatuzumab R-CHP. So, basically the O in R-CHOP was removed and substituted for this new drug called polatuzumab vedotin, and although many, many combinations similar to R-CHOP have been compared to R-CHOP over the past 20 years and failed, this regimen, polatuzumab R-CHP in the study called the POLARIX study actually was shown to improve what we call progression-free survival by about six percent. So, it may become a new standard of care for treating DLBCL, which is exciting, because we haven’t had one in over 20 years.

Katherine:                  

Right. That’s good news.

Dr. Kline:       

Long answer to a short question, sorry about that. Yes, it is good news.

Katherine:      

That is good news. What about stem cell transplants?

Dr. Kline:       

Good question. So, for newly diagnosed patients, in this era, we rarely if ever are recommending stem cell transplant or stem cell transplantation as part of initial therapy. There are rare circumstances, but for the vast majority of patients who are, people who are diagnosed with DLBCL, it’s not recommended.

Katherine:      

Where do clinical trials fit in?

Dr. Kline:       

It’s a really good question. I practice at an academic medical center, and so one of our missions is to advance therapy and make it better. There’s no way to do that without performing clinical trials, so I think for – clinical trials aren’t for everyone. As a matter of fact, most people with lymphoma are not treated in the context of clinical trials.

But certainly I think they are important to consider, and number one, it’s possible that the particular person might be involved with the clinical trial that is very successful and actually improves their outcome. I always tell people that I see that being involved with the clinical trial is also, to some extent, an altruistic endeavor. You’re helping your doctors learn more about how to treat a type of cancer, hopefully better, maybe not, you know? So, there is some altruism that goes into clinical trials as well. So, I do think that most people who are able should consider having a second opinion. Doesn’t have to be at an academic medical center, but at least with another doctor, where clinical trial options can be discussed.

An Expert Overview of DLBCL Treatment Approaches

An Expert Overview of DLBCL Treatment Approaches from Patient Empowerment Network on Vimeo.

How is Diffuse Large B-Cell Lymphoma (DLBCL) treated? Dr. Jason Westin provides an overview of current DLBCL approaches.

Dr. Jason Westin is the Director of Lymphoma Clinical Research in the Department of Lymphoma/Myeloma in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Westin, here.

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Transcript:

Katherine:                  

So, once it’s time to treat, then of course it’s time to think about treatment options. So, let’s walk through the types of therapy that are used today in DLBCL treatment. First of all, let’s talk about chemotherapy.

Dr. Westin:                 

Yeah. So, unfortunately, chemotherapy is still the – cornered the realm when it comes to DLBCL therapy, especially in the frontline setting. So, if a patient is newly diagnosed, no prior history of DLBCL, biopsy comes back and describes that’s what we’re looking at, the standard treatment, which has been around for about 40-plus years, is a combination of chemotherapy called CHOP, each letter representing a different medication. The antibody immunotherapy Rituxan, or rituximab, was added about 20 years ago.

So, the standard treatment for the past 20 years has been R-CHOP. And this has been tried and true. It’s been tested many, many times to try and improve this or to beat this. And R-CHOP has been less toxic than other alternatives or as good as other alternatives through many, many, many trials.

Now, late last year, in 2021, there was finally a randomized Phase III trial that showed, in addition of a targeted therapy in place of one of the chemotherapy drugs, had a slightly better progression free survival at two years. The targeted therapy here is a drug called polatuzumab. Polatuzumab is an FDA-approved therapy for large B-cell lymphoma patients in the US. Currently, as of the time we’re taping this, it’s approved for patients with relapsed disease. It’s not yet approved, based on this Phase III trial, but that may change in the coming months.

The improvement was modest. Around six percent of patients differing in terms of those who had progressed versus those who had not progressed in two years. So, not an earthquake, but R-CHOP or variations of R-CHOP are still a standard treatment for patients, outside of a clinical trial, of newly diagnosed diffuse large B-cell lymphoma.

Katherine:                  

And what about CAR T-cell therapy?

Dr. Westin:                 

The other treatment classes, the targeted therapies include CAR T-cell, or other antibody drug conjugates, immunotherapies, bispecific [antibodies] – there is a lot going on in new drugs and new drug development for DLBCL.

As of today, most of those therapies that are approved are looked at in patients that have already had a frontline chemotherapy approach and the cancer has come back. So, those are approved. But they’re either approved for patients in second line therapy – after having had one line, cancer comes back and now we’re in second line – or in third line therapy, two previous treatments and now we’re in third line treatment. There’s a lot of clinical trials, and I think we’ll talk maybe about clinical trials in a bit, that are exploring use of these targeted therapies, including CAR T-cells, including bispecific antibodies, including other targeted therapies as a potential for a frontline treatment.

But outside of a clinical trial, R-CHOP or versions of R-CHOP are still the standard today.

Katherine:                  

And what about stem cell transplant?

Dr. Westin:                 

Stem cell transplant’s been a second line therapy option, and it’s been the standard second line therapy for about 25 years. We’ll see this change in the coming years. There have recently been three randomized clinical trials comparing stem cell transplant versus CAR T-cell. All three of those reported out some information in late 2021, with two of them having final results, one of them having an interim report. And one of the final reports, one the interim reports, showed a significant improvement in chance of staying in remission in all the outcomes that were measured for CAR T-cell beating stem cell transplant.

So, we’re waiting to see how the health authorities view these clinical trials, if CAR T-cell potentially moves into second line treatment for a majority of patients instead of stem cell transplant. So, stem cell transplant’s been there, it’s tried and true. It has cured a significant portion of patients. However, CAR T-cells potentially are better and may be moving in the second line within the next year.