Tag Archive for: double hit lymphoma

How Do Different Diffuse Large B-Cell Lymphoma Subtypes Impact Treatment Options?

How Do Different Diffuse Large B-Cell Lymphoma Subtypes Impact Treatment Options? from Patient Empowerment Network on Vimeo.

How are diffuse large B-cell lymphoma (DLBCL) subtypes impacting treatment options? Expert Dr. Nirav Shah from the Medical College of Wisconsin explains key factors that help determine DLBCL subtype and the importance of knowing your subtype for optimal care. 

Dr. Nirav Shah is an Associate Professor at the Medical College of Wisconsin. Learn more about Dr. Shah.

[ACT]IVATION TIP:

“…know your subtype of diffuse large B-cell lymphoma, so you can understand what treatment is best for that variant.”

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Transcript:

Lisa Hatfield:

What are the subtypes of DLBCL, and how does that impact treatment options? 

Dr. Nirav N. Shah:

Yeah, so I think I may have talked about that a little bit earlier. So we call it diffuse large B-cell lymphoma, but it’s really not one disease, there are multiple subtypes, so one thing is a cell of origin, and this sort of says what part of the lymph node does this diffuse large B-cell lymphoma originate from. And so there’s something called the germinal center phenotype. The other one is called the activated B-cell phenotype and prognostically, these sort of behave differently. Currently, we’re treating them the same, but we’re hoping that in the future, we’ll actually have algorithms that are more refined so that they are giving the best treatment for each subtype.

I mentioned earlier that there’s a variant called double-hit lymphoma that we think is particularly aggressive, and for that variant, I would actually consider clinical trials as an option if they’re available to you, but outside of a clinical trial, we do give higher intensity chemotherapy regimens, there’s more than one standard of care in that setting. But, again, important to understand what is your DLBCL type and what are some of these other molecular mutations that might be there that would impact that frontline treatment. So my activation tip for this is to know your subtype of diffuse large B-cell lymphoma, so you can understand what treatment is best for that variant. 


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Understanding High-Risk DLBCL

Understanding High-Risk DLBCL from Patient Empowerment Network on Vimeo.

What is high-risk diffuse large B-cell lymphoma (DLBCL) exactly? Dr. Jane Winter explains progression of the disease, DLBCL subgroups, and treatment approaches that may bring high-risk DLBCL under control.

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 is high-risk DLBCL?   

Dr. Winter:

There are certain aggressive lymphomas that are more high-grade. And in recent years, we’ve identified a subset that has genetic changes in certain genes that lead to a very aggressive type of lymphoma that grows rapidly and is more difficult to cure with standard therapy. And what’s most important about identifying that subset is that it requires that at least most of our evidence is that the standard strategy that I just spoke about briefly in terms of what we use for transformed follicular lymphoma, the standard therapy we use for diffuse large B-cell lymphoma called R-CHOP where the “R” is standing for rituximab. 

Again, that antibody that targets a particular marker on the lymphoma cells, CD20 immunotherapy plus chemotherapy, CHOP chemotherapy which has been around for probably 50 years, this very standard backbone of treatment for diffuse large B-cell lymphoma is not sufficient. We don’t have head-to-head randomized phase three trials showing definitely that the more aggressive strategy is so much better, but most of the evidence is that standard R-CHOP just doesn’t do as well in curing these highly aggressive, and what we call high grade or double hit lymphomas.  

These are lymphomas that have these genetic changes, rearrangements in particular genes MYC and BCL2, and I like to think of it as MYC takes the brakes off of growth. So, it’s sort of the rapidly growing disease, and the BCL2 prevents the cells from dying. So, between that, you have a rapidly growing lymphoma that doesn’t stop. And so, that’s a special subgroup of diffuse large B-cell lymphoma. There are some other subcategories.  

Primary mediastinal, which tends to be a type of aggressive lymphoma that presents generally as a big mediastinal mass in the middle of the chest, usually younger patients, more often women than men, but still many, many men as well. So, high-risk generally for me means that it has a double hit. There’s MYC, M-Y-C, and BCL2 genetic changes. There are some other types, but that’s basically what I think of in terms of high-risk. When we think of garden-variety diffuse large B-cell lymphomas, there are some ways of categorizing patients into four different subcategories in terms of “risk.”   

The first of these was what we call the international prognostic index that was developed in the 70s based on patients who were enrolled on clinical trials. In those days, the diagnoses were probably not exactly what they are today in terms of how we categorize patients, but that is a set of clinical features that there’s a little app online and you can calculate whether a patient is high-risk, intermediate, low, low-intermediate risk. In this system remains fairly helpful, predictive. But, we have refined it significantly in modern times. 

And I have to say, not to toot my own horn, but one of my fellows, Dr. Zhao and I, a number of years ago using a database from the National Comprehensive Cancer Network, and patients who all treated with modern therapy and were diagnosed with modern techniques, we used that data to develop a new, improved international prognostic index. And this helps us better discriminate the four different categories, and it places greater weight on patient age, which is an important predictor, as well as the particular blood test result, the LDH, which is an enzyme that’s helpful in aggressive lymphomas and diffuse large B-cell lymphoma.  

And, this particular, what we call the NCCN-IPI, you can just put your age and LDH level and so on into this app and you just find it online, NCCN–IPI, and it will put patients into four different subgroups. And this predict outcomes and survival over a five-year period for these patients. It’s not hard and fast, like anything else, within every category. So, if you look at every patient in the low-risk group by the NCCN–IPI, there still are a few patients who will fail therapy, but the majority of patients will do very well.  

And, if you happen to be someone who is 80 years old with a high LDH and you fall into the high-risk patient group, the outcomes are not going to be as good, but that doesn’t mean every patient in that category fails treatment. So, there’s still gonna be some good outcomes. So, it’s helpful. These are guides, and they do help to identify patients who are, what we call, high-risk or high intermediate risk. So, this is another way of looking at predicting outcome apart from looking at whether a patient is what we call a “double hit” lymphoma. So, the double hit, I just want to make one point is that when a pathologist makes a diagnosis of diffuse large B-cell lymphoma, it is absolutely critical that that biopsy, the pathology be sent for a procedure called FISH.  

That stands for fluorescent in situ hybridization, and it’s a technique the pathologist can use, or special labs will use, to pull out, to identify those patients who have this very high-risk subset of lymphoma called the double hit with both a MYC and a BCL2 rearrangement. Whether a MYC and a BCL6 rearrangement falls into this same risk group, we’re deemphasizing that and really, it’s the double MYC and BLC2 group that’s the highest risk.  

An Expert Defines Diffuse Large B-Cell Lymphoma (DLBCL)

An Expert Defines Diffuse Large B-Cell Lymphoma (DLBCL) from Patient Empowerment Network on Vimeo.

What is diffuse large B-cell lymphoma? Dr. Justin Kline defines DLBCL from symptoms to staging and explains how the condition progresses through the body.

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 start by understanding what DLBCL is and how it progresses. How would you define DLBCL?

Dr. Kline:       

Well, diffuse large B-cell lymphoma is a malignancy of a normal counterpart cell called a B-cell, which is part of our immune system. Its job is to make antibodies, to help protect us from various types of infections. Diffuse large B-cell lymphoma, or DLBCL, initiates when normal B-cells acquire changes in their genetic machinery, like any cancer. And DLBCL is the most common form of non-Hodgkin lymphoma. We classify it as aggressive, as an aggressive lymphoma, which means if left untreated it tends to grow pretty quickly.

Katherine:      

How is it typically diagnosed?

Dr. Kline:       

Well, it varies. But like any cancer, a diagnosis requires some sort of a biopsy, either a surgical removal of a lymph node or a needle biopsy of a lymph node or another structure where the tumor seems to be growing.

Katherine:      

How does somebody know if they have DLBCL?

Dr. Kline:       

Well, there are certain symptoms that are more common amongst folks with DLBCL. And they’re not specific to DLBCL, they can be seen in other lymphomas, but they include symptoms like fatigue that’s unrelenting, unintentional weight loss, sometimes fevers, typically at similar times throughout the day, drenching night sweats, swollen lymph nodes, and then certainly pain in any area of the body that comes and doesn’t go. Those are some of the general symptoms.

Katherine:      

And how does the condition progress?

Dr. Kline:       

Well, as I mentioned, DLBCL tends to be an aggressive lymphoma, so sometimes folks will notice enlarged lymph glands that continue to grow and grow and grow. Sometimes they’re painful, sometimes not so much. DLBCL, it can really grow anywhere, so we think of it as a lymphoma and so involving lymph nodes, but DLBCL can grow in any organ, even outside of lymph nodes. And so it sometimes progresses locally, but it also can spread and start to grow in other areas of the body.

Katherine:      

And how is it staged, Dr. Kline?

Dr. Kline:       

Well, there’s a special staging system for all lymphomas that is somewhat similar to what folks might think of with solid tumors like a breast cancer, a lung cancer. But in other ways, it’s different.

The staging tools for DLBCL are really most importantly PET scans and CT scans, really PET scans and in some cases bone marrow exams or bone marrow biopsies. The PET scan is a very sensitive scan that uses radioactive glucose to identify very sensitively where in the body lymphoma might be growing, because lymphoma cells really preferentially prefer to use glucose as their primary energy source. So, they preferentially take up the radioactive glucose that’s given through the vein before the PET scan is taken.

As I mentioned, in some cases, a bone marrow test is also done, although less and less frequently. Which is good, because that’s a more invasive and uncomfortable test. And so folks who have early stage DLBCL that typically involves one lymph node group, like for example, a lymph node in the neck or several lymph node groups on the same side of the breathing muscle, of course you can’t see my breathing muscle here, called the diaphragm.

Those are stage I and stage II DLBCLs. stage III DLBCLs are those that involve lymph nodes on either side of the breathing muscle, so in other words, lymph nodes involved in the neck and then maybe in the groin area, where stage IV DLBCLs are those that involve sites outside of lymph nodes like the liver or the lungs or the bones.

Katherine:                  

What are the subtypes of DLBCL?

Dr. Kline:       

Well, that’s a good and somewhat complicated question. So there, probably most importantly, there’ve been two subsets, if you will, of DLBCL identified, and they really have to do with where along the normal maturation course a B-cell becomes lymphoma or where the DLBCL develops in that normal maturation course. Some DLBCLs arise from what we call germinal center B-cells, which are B-cells that are sort of just seeing their natural antigen or what they’re supposed to recognize.

And then there are DLBCLs that arise in more differentiated or more mature B-cells, and those are called activated B-cell type DLBCLs. So, there’s germinal center and activated, the B-cell type DLBCLs. And I don’t know that that’s super important for your listeners to know, but it is important because these two subtypes of DLBCL are driven by largely separate mutations or alterations in the DNA, and they also respond differently to initial treatment. There are other rare subtypes that involve specific mutations and genes like MYC and BCL2, and these are the so-called double-hit lymphomas. They’re officially classified as high-grade lymphomas, but they’re very similar to DLBCLs. There are other rare subtypes of DLBCL, for example, a type that comes on typically in young men and women called primary mediastinal B-cell lymphoma.

But I think for the sake of simplicity, the most common two subtypes are the germinal center derived and then the activated B-cell type of DLBCL.

Katherine:      

All right. That’s good to know, thank you. It helps us understand the disease a little bit better.

Dr. Kline:       

Good.

What Helps Determine a Patient’s DLBCL Treatment Path?

What Helps Determine a Patient’s DLBCL Treatment Path? from Patient Empowerment Network on Vimeo.

Since no two patients are exactly alike, how is DLBCL treatment determined? Dr. Jason Westin explains what factors he considers when determining a patient’s treatment path. 

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:                  

Since no two patients are exactly the same, I imagine then that their treatment approaches are different. So, what do you consider when determining the best treatment option for an individual patient?

Dr. Westin:                 

That’s a very important question. How can we personalize treatments in a way that gets us down to what a single patient needs, not both populations of thousands of patients, but the person sitting across the exam room.

Katherine:                  

Right.

Dr. Westin:                 

For first line DLBCL, someone who’s newly diagnosed, unfortunately the one size fits all of R-CHOP being the standard, or versions of R-CHOP, the new treatment that I mentioned having a slight improvement not yet approved by the FDA, there’s not as much customization or personalization outside of clinical trials as I would like. We’d love to be smarter and to be able to say, “Well, you have the subtype A of large B-cell, therefore you should get subtype therapy A,” or subtype B and you get subtype therapy B. We have more of a one-size-fits-all approach in our frontline treatment outside of clinical trials.

On clinical trials, sometimes patients will have a subtype of large B-cell. We talk about things called the cell of origin. We talk about things called double hit. There are specific subtypes of DLBCL that occasionally a clinical trial will target that subtype and have a therapy that’s supposed to work better in that subtype.

So, that’s another reason to consider clinical trials, is the ability to potentially to customize or personalize your therapy to go more specifically after what’s wrong with your cancer cells as opposed to having something that’s given as a shotgun approach to everyone. And the reason that R-CHOP is around for this long is that it works fairly well across the board in different subtypes. It’s not something that’s completely effective in one and completely ineffective in another.

But, in terms of personalizing therapies, clinical trials are an important thing to be considered. In the relapse space, with patients that have relapsed disease, there we have more potential to customize treatments and often that’s done based upon characteristics of the tumor or the patient’s preferences in terms of frequency of treatments, in terms of potential for side effects. There’s more that can be done if somebody’s already had a treatment and it came back. But clinical trials are a great way to try and customize, or to drill down in terms of specifics about your particular cancer.

Katherine:                  

Can you touch upon treatment side effects?

Dr. Westin:                 

Yes. Treatment side effects, obviously, are very important to our patients in terms of what does their quality of life look like while the therapy’s ongoing to try to get rid of this dread cancer. The side effects really depend upon what treatment we’re talking about. And if we focus on frontline treatments, the initial treatments being R-CHOP based treatments, side effects are chemotherapy side effects. And that includes low blood counts, white blood cells, red blood cells, platelets, risk of infection along with the low white blood cells, and risk of fevers prompting a trip to the emergency department for an evaluation.

Thankfully, that’s rare. Maybe one out of four or one out of five patients would have an infection during treatments. But if it happens, it can be serious. Fatigue, nausea – which is usually very well controlled with medications, but nonetheless has to be something we watch out for. And for many patients, it’s important to note that hair loss can occur from the chemotherapy. And that’s something that it’s easy to say, “Oh, I don’t care about that.” But for many people, when you look in the mirror and you see somebody else looking back at you, somebody that has a different physical appearance than you’re used to, it can be quite distressing.

That’s unfortunately part of many patients’ journey with the therapy for diffuse large B-cell lymphoma. In nonchemotherapy treatments – the targeted ones that I mentioned – these are the antibody drug conjugates, the targeted immune therapies, or in CAR T-cells, side effects can be very different, sometimes much less in terms of the side effects, other times completely different types of side effects. So, it really matters what type of treatment you’re talking about. And this is something you really want to clarify with your physician, with the nurse, with the PA.

“Tell me a lot of details about what I should expect when I’m feeling this. And give me reading materials so I can digest it, think about it, and figure out what questions I need to ask after we first discuss this.”

Katherine:                  

Yeah.

Dr. Westin:                 

The side effects really are an important part of the patient’s journey.

How Does Biomarker Testing Impact DLBCL Treatment Options?

How Does Biomarker Testing Impact DLBCL Treatment Options? from Patient Empowerment Network on Vimeo.

Biomarker test results may help guide diffuse large B-cell lymphoma (DLBCL) treatment options. Expert Dr. Loretta Nastoupil explains how biomarkers are currently used in determining an optimal treatment approach and how research efforts could help create more precise treatments.

Dr. Loretta Nastoupil is Director of the Lymphoma Outcomes Database in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Nastoupil, here.

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Transcript:

Katherine:

What about biomarker testing results?

Dr. Nastoupil:

So, in a perfect world, we would be able to take a patient’s specific tumor, sequence it, and provide a recipe or a solution to solve the problem. And that’s what a biomarker is.

It’s something that’s unique to the patient’s given tumor that then would inform what is the best treatment. So, we’re lacking in some ways a perfect scenario. What we do have, as what I’ve mentioned, some molecular studies where we can look for specific genes or rearrangements in the genes that may help us predict the future.

And in diffuse large B-cell lymphoma, one of the most common examples of this is what we call double hit where we’re looking for two genes – MYC, which is M-Y-C, and either BCL-2 or BCL-6. These are genes that we all have. It’s just the lymphoma has moved these genes into sort of more of a prime real estate location that makes it a little bit more resistant to standard treatments.

So, if you move those genes in that tumor DNA, we call that our rearrangement. And we pick that up based off a FISH study. And if both of those features or all three of those features are there, we call it a double or triple hit.

That’s a potential biomarker that may suggest that particularly R-CHOP or standard treatment may not be the best strategy. There’s some limitations to that conclusion in that that’s not true for every patient. For about 20 percent to 30 percent of patients with double hit features, they’re going to do really well with R-CHOP.

So, that’s why we are lacking in how effective these biomarkers are. And it would be great if we had additional biomarkers that were more precise or could tell us more than just that the standard may not be optimal.

So, that’s where we’re spending a great deal of time and effort in our research efforts just trying to identify biomarkers that may tell us what’s the best approach for a given patient or what we like to call personalized medicine. 

Understanding Diffuse Large B-cell Lymphoma (DLBCL) and Its Subtypes

Understanding Diffuse Large B-cell Lymphoma (DLBCL) and Its Subtypes from Patient Empowerment Network on Vimeo.

What should patients know about diffuse large B-cell lymphoma (DLBCL) and its subtypes? Expert Dr. Loretta Nastoupil defines DLBCL, discusses the subtypes of DLBCL and reviews the potential impact on treatment options.

Dr. Loretta Nastoupil is Director of the Lymphoma Outcomes Database in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Nastoupil, here.

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Transcript:

Katherine:

So, let’s start with a basic question, what is diffuse large B-cell lymphoma or DLBCL?

Dr. Nastoupil:

That’s a really important question. And I spend a lot of time when I first meet patients explaining to them there are a lot of different terms that are thrown around in lymphoma. Particularly, non-Hodgkin lymphoma is a term many patients will hear and even use. And I remind them that that is sort of an umbrella term that describes essentially every lymphoma that’s not Hodgkin lymphoma.

So, it’s really important to recognize that there are unique types of large cell lymphoma. And almost everything that we care about in terms of what the treatment will look like, whether or not we’re aiming to cure someone, or just maintain adequate disease control is primarily focused on the type of lymphoma someone has.

So, diffuse large B-cell lymphoma is the most common lymphoma subtype. Just in terms of its descriptive name, it is a B-cell cancer. And it is comprised of large cells that are essentially effacing or replacing the architecture of a lymph node.

There are different types, which I’m sure we’ll discuss. But, again, diffuse large B-cell lymphoma is our most frequent lymphoma we encounter.

Katherine:

What is B cell? What does that mean?

Dr. Nastoupil:

Sure. So, stepping back a little bit, I think most people when they know or have known someone with cancer, it is described as the organ it originates in. So, breast cancer’s a great example. That usually is breast tissue that is abnormal. It has malignant potential. And if it spreads beyond its capsule and specifically goes to a lymph node or another organ, generally that’s bad news.

Lymphoma is a cancer of the immune system. And there are various types of immune cells. B cells – they mature on and become plasma cells when they’re behaving normally. And their job is to generate antibodies so that we can develop immunity from exposures or infections we’ve had and we’ve recovered from.

So, if you develop a cancer in the B cell, depending what stage of development – if it’s a stem cell, for instance, that can lead to acute leukemia. If it’s an immature B cell, meaning it has not developed into a plasma cell, that’s, generally, where diffuse large B-cell lymphoma arises. So, these cells tend to live or spend most of their time in lymph nodes because they’re trying to mimic the behavior of a normal B cell where they’re waiting there for that exposure to happen.

So, these are generally not cancers that we try to cut out before they spread. They’re not spreading cancers in terms of how we generally think of those, meaning you’re not going to use surgery to treat it. And, oftentimes, there are malignant B cells kind of dispersed throughout the body because if you think about how your immune system should work, it should be able to fight off an infection anywhere and everywhere.

So, I think those are key things to keep in mind because oftentimes patients will have widespread involvement or lymph node involvement or bone involvement, and that’s just the nature of the disease and not necessarily something that is so far progressed we didn’t catch it early enough.

Katherine:

I see. Are there subtypes of DLBCL?

Dr. Nastoupil:

Yes, absolutely. So, again, stepping back, over the last 20 years, we have tried to understand why we’re able to cure about 60 percent of patients. But for the 40 percent that were not cured with standard treatment, their outcomes were generally poor, meaning most of those patients died as a result of their lymphoma.

And we’ve approached all of them the same. So, that would imply to us that there’s something inherently different about the large cell lymphoma cases that don’t respond to standard treatment. So, an attempt to try and define who those patients are before we initiate treatment, as technology has evolved, we’ve interrogated some of those biopsy samples to try and understand is there an underlying biologic rationale as to why some patients would have very, very disparate outcomes?

So, what we’ve learned is there are genes that are differentiated between different subtypes of large cell lymphoma. And we’ve described those subtypes based off those gene expression patterns. So, there is a germinal center type of large cell lymphoma. There’s a non-germinal center or activated B-cell type.

And then it gets much more complicated meaning there’s probably far more than just two subtypes. Right now, we’re describing at least five different subtypes. I think what’s important for patients to know is that we view this in terms of being able to predict who’s not going to have the typical course. And if we can define who they are, we might pursue something different, including potentially a clinical trial.

So, the subtypes I care the most about right now in terms of defining are the double hit or double expressors, those with other features that might lend itself to targeted therapy.

So, this is an evolving field and will continue I’m sure – that will have more subtypes defined over time. 

An Expert Review of DLBCL Research and Treatment Advances

An Expert Review of DLBCL Research and Treatment Advances from Patient Empowerment Network on Vimeo.

What’s the latest in diffuse large B-cell lymphoma (DLBCL) treatment advances? Expert Dr. Robert Dean provides an update about emerging DLBCL research and explains recent treatment approvals for relapsed DLBCL patients.

Dr. Robert Dean is a hematologist/medical oncologist at Taussig Cancer Institute at the Cleveland Clinic. Learn more about Dr. Dean, here.

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Transcript:

Katherine:

Is there emerging DLBCL research that you feel patients should know about?

Dr. Dean:

I would say, “yes.” One of the things that has really been striking for me in the last few years alone in caring for patients with large B-cell lymphoma is how we’ve gone from a more surface-level understanding as we’ve been talking about what some of the differences are between different cases of large B-cell lymphoma to being able to get a better readout of why the lymphomas sometimes behave the way they do.

I want to be careful to make sure that patients who might be listening to this understand that we still don’t have a crystal ball. We can’t review their biopsy, look at their scans, and tell you, “I know that if you get R-CHOP you’re going to be cured.” Or if they’re a high-risk situation we can’t look into a crystal ball and tell them, “I know that R-CHOP won’t work for you, and you should do this tougher, more intensive treatment.”

We still see a lot of outcomes that we can’t necessarily predict from those other kinds of tools. They just give us a better sense of what the odds are for people as we’re at the start trying to make decisions about what to do. Another element that has really been striking has been the introduction of engineered T-cell immune therapy, which has provided an option for cure for some patients that otherwise we wouldn’t have had an option, and worked for about half the patients that go through it overall.

What’s coming down the road in clinical trials that are still ongoing is information that’ll help us decide if that approach to treatment should move to being second in line instead of a stem cell transplant for some patients, and they’re even doing studies looking at whether, for very high-risk patients, adding a CAR T-cell treatment onto the end of initial chemotherapy leaves them better off in the long run.

So, those are questions that will take some time to answer with ongoing studies, but I think are really exciting because they’re taking advantage of some of these newer treatment approaches that we know are helping some patients when their first attempts at treatment didn’t work and seeing if they might leave them better off if we use them earlier in the process.

There are other studies ongoing looking at seeing if we can improve upon the results that we get with treatments like R-CHOP as the first pass at treatment. Many such studies have been done and have not shown any benefit by adding this drug or that to the standard R-CHOP treatment, but there have been a few new drugs approved for treating people with large B-cell lymphoma after it’s relapsed in the last few years. For example, one called polatuzumab vedotin. Another combination of the drug lenalidomide and a new antibody-based drug called tafasitamab.

And then there’s another drug called loncastuximab. So, there’re studies going on with all of those looking at whether they offer more benefits to patients if we use them earlier in the game. 

Key Steps Following a DLBCL Diagnosis

Key Steps Following a DLBCL Diagnosis from Patient Empowerment Network on Vimeo.

What are key steps to take after a diffuse large B-cell lymphoma (DLBCL) diagnosis? Expert Dr. Robert Dean shares advice for newly diagnosed DLBCL patients to access optimal care.

Dr. Robert Dean is a hematologist/medical oncologist at Taussig Cancer Institute at the Cleveland Clinic. Learn more about Dr. Dean, here

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Transcript:

Katherine:

Yeah, of course. What three key pieces of advice would you have for a patient who’s just been diagnosed with DLBCL?

Dr. Dean:

The first, I would say, is always consider getting a second opinion. I would say that’s true for a patient who’s receiving care with a local oncologist who sees and treats all forms of cancer and who’s very close to home. But I would say that’s true for someone who comes and sees me as an oncologist who treats only lymphoma patients. You should never worry about hurting your doctor’s feelings by going and talking to someone else to get another perspective on their case. The second is that they should make sure that their biopsy has been checked for the other tissue-based predicting factors that we talked about earlier that can help give a better idea of whether their chances of cure are higher or possibly lower with standard R-CHOP treatment.

And if they’re in a higher-risk group that might have a lower chance of cure with R-CHOP, then they should ask, “should I be receiving a different kind of treatment?” And then, the third thing I would say is, they should always ask, “is there a clinical trial that’s a good fit for my situation. And if there isn’t one here, is there one somewhere else that’s worth me considering even if it might mean me traveling somewhere?”

Katherine:

Right.

Dr. Dean:

There’re always a lot of clinical trials around. And if there’s a good clinical trial that’s a fit for someone’s medical situation, and I would say, if it’s pretty close to the care that they need already and is asking an additional question and possibly providing an additional element to the treatment that may be helpful and that will help us learn something along the way, then in my mind that’s the best-case scenario. 

Relapsed DLBCL Treatment: What Are the Options?

Relapsed DLBCL Treatment: What Are the Options? from Patient Empowerment Network on Vimeo.

What are the treatment options for relapsed diffuse large B-cell lymphoma (DLBCL)? Expert Dr. Robert Dean explains approaches for relapsed DLBCL patients and considerations that may alter the treatment course. 

Dr. Robert Dean is a hematologist/medical oncologist at Taussig Cancer Institute at the Cleveland Clinic. Learn more about Dr. Dean, here.

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Transcript:

Katherine:

Are treatment considerations different for patients with relapsed disease?

Dr. Dean:

I’d say that they’re similar in a lot of ways. The first is, in my mind, again, is the patient that I’m seeing somebody who could potentially tolerate treatment that would be given with the goal of trying to cure their lymphoma on a second try?

Some patients with relapsed large B-cell lymphoma can be cured with the most common standard second-line approach, which is to get them back into remission with some standard chemotherapy, and then to follow that with a very intensive course of high-dose chemotherapy as a one-time treatment that’s given with a stem cell transplant using the patient’s own preserved healthy bone marrow stem cells. That treatment’s effective in about half of patients that can undergo it and you need to be pretty fit medically and in an overall physical sense to be able to get through that treatment okay and have a good healthy recovery afterward.

So, it’s not for everyone, but it is doable in a lot of patients. The other questions or considerations that I think are important are if a patient is sort of on the border in terms of their overall health and their willingness to undergo really rigorous intensive treatment as a second try.

We have to look, in a balanced way, at what their goals are as an individual and what it’s going to take for them to try to reach those goals. I don’t easily back away from recommending to someone that I think has a shot at cure that they should go for it if they’re medically in reasonable shape to try for that. But there’re some people who, after their initial course of treatment, decide that they don’t want to pursue intensive treatment anymore and would rather go with a lower-intensity approach that might not have the potential for cure, but that wouldn’t be as demanding of them physically or logistically.

The logistics are another factor for some patients because most patients with large B-cell lymphoma can get treated with a standard treatment approach like R-CHOP as their initial treatment at someplace that’s easily accessible to them where they live.

But the advanced treatments that are used to try to cure patients with relapsed large cell lymphoma, like a stem cell transplant, or like engineered CAR T-cell therapy, are only offered at large hospital-based cancer centers. And for some people, signing up to go and undergo that kind of treatment, to go through a long hospital stay, to be far away from family and home for a long time like that, and then have a longer recovery afterward, is something that they aren’t always comfortable with and really need some coaching through to figure out how all that aligns with their goals.

Most people, in my experience, are willing to go through what they have to if we think, and if they feel like, they’ve got a decent shot at getting cured on a second try. But that’s part of the discussion that we have when we’re talking about what their options are because there are less intensive approaches available.

They just don’t carry that same potential for cure.

Factors That Guide a DLBCL Treatment Decision

Factors That Guide a DLBCL Treatment Decision from Patient Empowerment Network on Vimeo.

What factors impact diffuse large B-cell lymphoma (DLBCL) treatment decisions? Expert Dr. Robert Dean shares key considerations, such as a patient’s health and risk factors, in determining DLBCL treatment options.

Dr. Robert Dean is a hematologist/medical oncologist at Taussig Cancer Institute at the Cleveland Clinic. Learn more about Dr. Dean, here.

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Transcript:

Katherine:

What are the main factors you take into consideration before a treatment approach is decided on?

Dr. Dean:

From the perspective of the biology of the lymphoma itself, it’s making sure that the tissue samples have been worked up in a thorough enough way to give us the information that we’ve already been discussing, especially to rule out or to identify when there’s a double-hit kind of chromosomal change in the lymphoma cells because for most patients that abnormality does call for a different approach from the usual R-CHOP treatment.

And not all treatment centers are equipped to give those more intensive treatments. So, someone who’s got a standard and, what I would consider to be a lower-risk case of large B-cell lymphoma, could be served very well receiving standard outpatient R-CHOP chemotherapy under the care of a local oncologist who’s taking care of patients in their community.

But someone who’s got a higher-risk situation, like a double-hit large cell lymphoma, would probably be better served to at least be seen in consultation by someone who’s got more specialized expertise in treating higher-risk lymphoma patients at a referral center. Beyond that, you have to also take into account a number of patient factors. Because diffuse large B-cell lymphoma is potentially curable with standard treatments, even the high-risk cases that’s true.

The first question that I always ask myself when I’m evaluating a new patient is, “is there anything about this person’s health that would make it impossible or highly risky for them to tolerate the standard treatments that we use to try to cure our patients?” If they’re a candidate for curative-intent treatment, then we decide what the most appropriate treatment would be from there.

The second question is, as we talked about before, is R-CHOP a reasonable standard approach for that patient, or do they have other risk factors that would suggest that you’d need to do something different, such as rituximab and EPOCH treatment or another more intensive regimen for a double-hit case? There’s a subgroup of patients who have large cell lymphoma that arises in the testicle in men and those patients are at increased risk for having the lymphoma show up later as a recurrence in the nervous system. There are studies that suggest that if you add some elements to the treatment to try to prevent that, that it may reduce that risk.

Katherine:

Okay.

Dr. Dean:

And then I think the last thing I would say is, with any patient I consider, are they eligible for a clinical trial that’s looking at a novel approach to treating large cell lymphoma and, if there is a clinical trial that they’d be eligible for, is that a good fit for their situation?

We know that our best treatment approaches that we currently have for standard of care right now still don’t prevent relapses in some patients and we want to continue to be able to offer our patients better treatment approaches and the only way that we can do that is by testing new ideas in clinical trials. So, I always ask myself, “Is this patient eligible for a trial, and do we have a trial or do I know of a trial that would be a good fit for them?” 

How Does Your DLBCL Subtype Impact Your Treatment Options?

How Does Your DLBCL Subtype Impact Your Treatment Options? from Patient Empowerment Network on Vimeo.

How does a patient’s diffuse large B-cell lymphoma (DLBCL) subtype impact their treatment options? Expert Dr. Robert Dean explains the most widely used DLBCL treatment approach as well as options for highly aggressive subtypes.

Dr. Robert Dean is a hematologist/medical oncologist at Taussig Cancer Institute at the Cleveland Clinic. Learn more about Dr. Dean, here.

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Transcript:

Katherine:

So, how does a patient’s subtype impact their treatment options?

Dr. Dean:

It’s getting there slowly. Right now, the most widely used initial treatment for patients with diffuse large B-cell lymphoma is still the monoclonal antibody rituximab (Rituxan) and the combination chemotherapy regimen called CHOP, or R-CHOP as it’s called for short all together. And for patients with lymphomas that are not the so-called double-hit type, at least in our center, R-CHOP is still the standard, most commonly used approach to treat those cases. For the double-hit cases, studies have shown that their results with R-CHOP treatment are significantly worse than what you see with the cases that are not double-hit lymphomas.

And because of that, a lot of lymphoma treatment programs have looked to other approaches to treatment that are a little more intensive, similar to what we use for highly aggressive lymphomas, such as Burkitt lymphoma, to see if we can do better for those patients. And the one that we most commonly use here at our center for the double-hit lymphoma cases is a regimen that’s called R-EPOCH, where you take the drugs that are in the R-CHOP, add an extra chemotherapy medicine, and give them in a different manner that provides a more prolonged exposure to the chemotherapy drugs with each round of treatment and also provides for some tailoring of the chemotherapy doses from one round of treatment to the next.

There aren’t any great controlled trials yet that prove that stronger treatment regimens like R-EPOCH are better for the double-hit cases of large cell lymphoma than the tried-and-true R-CHOP regimen that’s used for most other situations.

But there are what we call uncontrolled studies or retrospective studies that have looked at patients treated with those higher intensity regimens, and they at least suggest that patients treated with those approaches look like they do better than what you would have expected with the R-CHOP approach. And then there are a few less common subtypes of large cell lymphoma that are more specific and are treated in more unique ways.

For example, large B-cell lymphoma can arise in the brain only in rare cases and when that occurs it’s treated using an approach that’s really geared toward ensuring that you’re giving chemotherapy drugs that can effectively get into the brain tissue and attack the lymphoma cells there. Once in a while, you see someone who’s got both of those situations going on at once, lymphoma growing in the lymph node system or other places in the body outside of the nervous system, and lymphoma growing in the nervous system at the same time, and you need to make adjustments in how you treat those cases, too. 

What Are the Subtypes of DLBCL?

What Are the Subtypes of DLBCL? from Patient Empowerment Network on Vimeo.

What are the subtypes of diffuse large B-cell lymphoma (DLBCL)? Expert Dr. Robert Dean provides an overview of DLBCL subtypes and how treatments and outcomes can vary by a patient’s individual disease.

Dr. Robert Dean is a hematologist/medical oncologist at Taussig Cancer Institute at the Cleveland Clinic. Learn more about Dr. Dean, here.

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Transcript:

Katherine:

Dr. Dean, welcome. Would you please introduce yourself?

Dr. Dean:

Certainly, and thank you for having me. My name’s Rob Dean, and I’m a hematologist and medical oncologist and a staff physician at the Cleveland Clinic Taussig Cancer Institute.

Katherine:

Excellent. Thank you. Let’s start with looking at understanding and treating DLBCL. What are the subtypes of DLBCL?

Dr. Dean:

The classification of diffuse large B-cell lymphoma has gotten a little more complicated as our understanding of it has gotten deeper. Once upon a time going back maybe 15, 20 years an awful lot of cases were sort of lumped together under the broad label of diffuse large B-cell lymphoma and we always understood in the field that some patients did very well and were cured with the standard treatments of the time and that those treatments didn’t work as well for some patients.

And it’s taken years to get to a somewhat deeper understanding of what the underlying differences are in those cases that help to explain why our treatment outcomes differ for different patients, and I would say that’s feeding forward into trying to identify better treatment options for the patients who are in higher-risk groups. So, one way of understanding the heterogeneity in diffuse large B-cell lymphoma, the differences between cases, is to think about the way in which the normal cells of the immune system that turn into this kind of cancer develop. If you think about the old Time-Life Magazine illustration of the evolution of man where you see the series of figures drawn from left to right going from sort of more primitive, kind of a –

Katherine:

Ape-like.

Dr. Dean:

– ape-like figure to a progressively more modern-looking human standing upright and walking on just their legs. The way that these immune cells, which are the antibody-making B cells of the immune system, develop from a more primitive cell, you can think of it in similar terms. And we understand that cases of diffuse large B-cell lymphoma most commonly arise from a couple of points in that process of maturation that these cells are passing through as they go from the most primitive form that they take to their most mature functional form in the end.

So, one of those subgroups is something called the germinal-centered B-cell. And that involves the part of the maturation process where these immune cells have left the bone marrow, passed into a lymph node, and are interacting with other immune cells as part of their education and development process.

When the cells mutate at that stage of their development and turn into diffuse large B-cell lymphoma, the cure rate for patients with large cell lymphomas coming from that stage of immune cell development tends to be a little higher with standard treatments. When the lymphoma cells arise from an immune cell that has passed beyond that point in the maturation process to what is referred to as an activated B-cell, then the cure rates with standard treatment historically have been a little lower.

And so, you can look at markers on the lymphoma cells, or the activation of different genes in the lymphoma cells, to try to determine whether they came from an immune cell that was in one or the other of those points in its maturation process. And we know that that correlates with outcomes. So, that’s one of the main breakdowns that have become possible in understanding sort of what’s going on under the hood in diffuse large B-cell lymphoma and why do we see different outcomes in different patients.

Katherine:

Right.

Dr. Dean:

The other major change comes from understanding that for cases of large B-cell lymphoma there are common chromosomal changes that result in turning on specific genes. And if some of those genes are present in the right combination, that can create a much more rapidly growing and more chemotherapy-resistant form of large B-cell lymphoma. The two genes that are most commonly involved in that kind of a change are something called BCL-2 which, when it’s turned on abnormally, helps protect the lymphoma cells from being killed or being sort of triggered into dying by chemotherapy medicine.

And another gene that’s called MYC, or M-Y-C is how that’s spelled, and what that gene does is it tends to cause the cells to proliferate more rapidly.

It turns on other pro-survival figures and controls a pretty broad range of different programs that drive the cells to grow more quickly. So, when you’ve got both of those changes at the same time that’s sometimes referred to as a “double-hit lymphoma.” And large cell lymphomas with that double-hit kind of chromosome change have been shown in studies to have a significantly lower cure rate with our most commonly used standard treatment for this form of lymphoma, what we call R-CHOP.

So, being able to recognize those changes in cases of large B-cell lymphoma is important nowadays, both in terms of being able to share prognostic information with patients, to be able to tell them what we think the likelihood of not just getting into remission but eventually being cured will be. And also, for some situations, considering whether a treatment other than the standard R-CHOP regimen might be a better option. 

What Is Diffuse Large B-cell Lymphoma (DLBCL)?

What Is Diffuse Large B-cell Lymphoma (DLBCL)? from Patient Empowerment Network on Vimeo.

What is diffuse large B-cell lymphoma (DLBCL) exactly? Dr. Jean Koff shares information about this specific type of lymphoma and explains why subtypes of DLBCL are important in determining optimal therapy.

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

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Transcript:

Katherine Banwell:

Hello, I’m Katherine Banwell, your host for today’s program. Joining me is Dr. Jean Koff. Dr. Koff, would you introduce yourself?

Dr. Koff:

Hi, I’m Dr. Jean Koff. I’m a lymphoma specialist and clinical researcher at Winship Cancer Institute of Emory University.

Katherine Banwell:

Great. Thank you for joining us. Well, let’s start with a definition. What is diffuse large B-cell lymphoma?

Dr. Koff:

So, we may want to back up and actually define what lymphoma is, because that may be unfamiliar to patients who are just getting a new diagnosis. So, lymphoma is a pretty general term, but it refers to a cancer that arises from white blood cells called lymphocytes. And normally these lymphocytes are part of your immune system. Normally they help to fight infections and even tumors. But sometimes in some patients often for reasons we don’t fully understand these lymphocytes, these white blood cells, part of your normal immune system can grow out of control to the point that they become a cancer. And when they do that, that’s called a lymphoma.

So, diffuse large B-cell lymphoma or DLBCL, is the most common, aggressive form of lymphoma. And we call it aggressive because it tends to grow quickly, and it tends to cause problems quickly.

Katherine Banwell:

Are there subtypes?

Dr. Koff:

There are and there are several different ways that you can subdivide DLBCL. One of the most common ways that DLBCL researchers and clinicians think about it is breaking it up into ABC and GCB subtypes. And what these subtypes are, are reflections of how the tumor expresses different genes and that makes it potentially susceptible to different types of therapy. Although we’re still trying to figure out the best way to target these different subtypes. You can also divide DLBCL up by other genes that it may express.

Patients may be familiar with the term double hit lymphoma that refers to a large cell lymphoma that has re-arrangements of certain genes, mainly MYC and either BCL-2 or BCL-6.

And then, there are other definitions that we can apply to DLBCL based on where the lymphoma arises. So, as you can see, there are lots of nuances into subdividing, this disease. There are lots of different varieties, and there are lots of subtleties. But one of the main breakdowns is between ABC and GCB.