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.

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

Factors that Guide a DLBCL Treatment Decision

How Does Your DLBCL Subtype Impact Your Treatment Options?

 
Key Steps Following a DLBCL Diagnosis


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. 

What Are the Stages of DLBCL?

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

Diffuse large B-cell lymphoma (DLBCL) care involves the use of a specific staging system. Expert Dr. Loretta Nastoupil shares insight about the DLBCL staging system and explains what is occurring in the body during each stage.

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.

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

Factors that Guide a DLBCL Treatment Decision

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

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

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


Transcript:

Katherine:

What are the stages of DLBCL?

Dr. Nastoupil:

So, we currently use what’s called the Ann Arbor staging system. And, again, this is very different from the staging applied in solid tumors.

And so, the way we define stage is based off where the tumor is in relationship to the diaphragm. So, if you have the disease just in lymph nodes and it’s all confined to one side of the diaphragm, it’s either going to be stage I or II. And how we distinguish between I or II is just really not are they in close proximity and something that we would fit in one radiation field.

If you have disease that’s above and below the diaphragm, that’s generally at least stage III. stage IV is generally when it’s now outside of the lymph node. So, what we call extranodal location. So, those are generally organs, lung, liver, skin, bone, etcetera.

It can be very complicated in that you could have just one extranodal site. So, say you just have stomach involvement, or you just have one area of the bone. That could be a 1E.

So, it’s important to recognize every patient has a stage. What that means is whether or not we would give a full course of therapy in terms of systemic treatment that goes through the vein or maybe a shortened course in radiation is dependent on that stage. 

What Are the Goals of DLBCL Treatment?

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

A diffuse large B-cell lymphoma (DLBCL) treatment plan may have different goals depending on the patient. Expert Dr. Loretta Nastoupil provides an overview of factors that play into treatment decisions and shares information about current and emerging DLBCL 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.

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

Factors that Guide a DLBCL Treatment Decision

DLBCL Treatment Decisions: What’s Right for You?


Transcript:

Katherine:

Many factors come in to play when making a treatment decision, including a patient’s age and overall health. So, let’s walk through some of these considerations. Let’s start with treatment goals. What does this mean exactly? And what are the goals of treatment for DLBCL?

Dr. Nastoupil:

Great questions. For diffuse large B-cell lymphoma, my goal was that I want to eradicate this disease with one course of therapy. Now one course of therapy, again, may mean six cycles of treatment, or it may mean three to four plus/minus radiation. And that kind of gets back to the discussion we just had with stage. But the goal is to make it go away and never come back. Now, oncologists are eternal optimists.

And I saw this because we would not be oncologists if we weren’t always focused and hoping for the best outcomes for our patients.

Katherine:

Sure.

Dr. Nastoupil:

So, we, generally, when we’re counseling patients tend to keep the focus on what is the chance that I can cure this, and we use words like cure oftentimes. But there’s always those caveats. And those caveats are – we can’t really look into our crystal ball and predict the future for every given patient. So, we use tools to help us risk stratify patients, meaning if we took 100 people like a given person, we could predict the outcome for the majority of those patients.

So, with diffuse large B-cell lymphoma with no high-risk features – so, that gets back to the molecular subtype. Do they have double hit features – yes or no? The stage and something we call IPI, International Prognostic Index, that takes into account some clinical features. As you mentioned, patient specific factors, their age, their stage, some lab values, whether or not they have more than one extranodal variable. Then we can generally predict.

Again, if I have 100 patients with good risk IPI, 80 percent of them are likely to be cured and alive and well five to 10 years later. If I have someone with poor risk features that may not change exactly what I do for that patient, but that may help them and me in terms of should I be pursuing a trial to potentially have access to something that’s better than this standard option? Or how does this impact their planning?

Some people are close to retirement. Some people have specific life goals, such as a wedding or an anniversary that sometimes we use those sorts of calculators to best predict the future to inform some of that treatment. So, those are what we call sort of the characteristics coming into treatment.

There are comorbidities or sort of concomitant medical problems, such as heart disease, sometimes diabetes. But, generally, more often than not, it’s how healthy your heart is because my objective with treatment is to cure this.

Cure generally results from chemotherapy. And we can spend some time talking about why have we not moved away from chemotherapy in this disease? But, generally, that does involve chemo because that’s generally how I can eradicate this tumor.

But there are certain situations where that chemo may not be beneficial to a given a patient. It usually has to do with how healthy their heart function is at baseline. So, again, we look at all of these factors. What is their risk with the disease? What is their risk from the toxicity of treatment? And am I able to achieve that goal, which is to eradicate the disease?

Katherine:

Well, let’s talk about chemotherapy. Why is that still part of the regimen in a treatment plan?

Dr. Nastoupil:

Yes, I’m going to borrow an analogy that one of my colleagues Jason Westin uses all the time. The CHOP chemotherapy that is the backbone of our treatment for diffuse large B-cell lymphoma was developed in 1976.

There is no other technology that we would commonly use in our day to day. You wouldn’t still be driving your car you had in 1976. Clearly, our methods of communication in regards to phones have changed dramatically. So, why are we still using chemotherapy that was developed in 1976?

Katherine:

True.

Dr. Nastoupil:

Well, it’s not for lack of trying. Over the last four or five decades, we have been trying to improve upon this. And it works. It works for at least 60 percent of patients. When we tack on targeted therapy, such as immune

therapy where we use an antibody that will stick to the surface of a marker on that lymphoma cell and then use the immune system to do some of the heavy lifting, we can probably improve those cure rates from 60 percent to potentially as high as 80 percent. That’s really been the only substantial improvement we’ve made.

Now, there is one caveat. So, just recently, we heard a press release of the POLARIX study, which is the first trial in the last four decades that could potentially replace R-CHOP as the standard of care.

We don’t have the full results yet. It’s essentially utilizing a drug called polatuzumab, which is an antibody drug conjugate. It’s essentially chemo on a stick. But we’re delivering chemo specifically to (CD)79b, which is a target on B cell lymphomas and modifying the CHOPs. We’re not getting rid of chemo altogether. We’re dropping one of the chemotherapy agents and replacing it with this targeted agent. So, it’s essentially CHOP plus rituximab and polatuzumab might be the new standard.

But, again, that’s based off many, many efforts to try and replace CHOP. And we’re making slow incremental improvements, but we’re still keeping the therapies that tend to work. 

Essential Testing Following a DLBCL Diagnosis

Essential Testing Following a DLBCL Diagnosis from Patient Empowerment Network on Vimeo.

Following a diffuse large B-cell lymphoma (DLBCL) diagnosis, essential testing should follow. Expert Dr. Loretta Nastoupil explains DLBCL tests that help determine prognosis and guide treatment options for each patient.

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.

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

Key Steps Following a DLBCL Diagnosis

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

Expert Advice for Newly Diagnosed DLBCL Patients

Expert Advice for Newly Diagnosed DLBCL Patients


Transcript:

Katherine:

Let’s look into testing for a moment. What tests are essential when making a diagnosis?

Dr. Nastoupil:

So, at the beginning, we clearly have to have tissue. I always say, “Tissue is the issue.” So, we may have features that are suggestive of lymphoma. And even sometimes radiologists will describe a CT scan or an X-ray and say, “This looks very suspicious for lymphoma.” But unless we actually have a biopsy that confirms lymphoma, we won’t go as far as to render a diagnosis in the absence of a biopsy.

Now our biopsy approaches have evolved over the last few years. The gold standard or what I would consider to be the best approach currently is to actually have an incisional biopsy meaning we find a lymph node that looks suspicious.

And we either remove the entire lymph node or a large section of that lymph node to render a diagnosis because there are various things we need to do to that lymph node.

So, generally, we do what’s called immunohistochemistry staining. So, we stain either surface markers of those cells or markers within the cell because cancer is defined as having an abnormal clone or a population of cells that all have the same features. And they’re able to survive even if the host is not thriving.

So, that’s, essentially, what we’re trying to define. Are there cells in this lymph node that are all the same? And what features do they share in common? And then we will also do something called flow cytometry where we’ll take these cells and essentially sort them according to those surface markers. And that will also tell us – is this a B-cell clone, a T-cell clone, and what features would distinguish one lymphoma from another?

And the last thing that we need tissue for are what we call molecular studies, where we may learn about either genes that are rearranged or mutated within those cells that, again, may help us further classify the lymphoma and, again, group them into higher or potentially lower risk groups.

Katherine:

What do the results of these tests tell us about prognosis and treatment choices?

Dr. Nastoupil:

So, again, everything kind of hinges on what type of lymphoma we’re facing. So, for instance, diffuse large B-cell lymphoma is what we call an aggressive lymphoma. So, what does that mean? It can grow very quickly. It can take over the patient in terms of resources. So, generally, patients will have weight loss and sometimes even constitutional symptoms or B symptoms, such as night sweats and fevers, fatigue.

In the absence of treatment, it is universally fatal. Now, that timeline can vary from one person to another. But, generally, within a year, if we don’t treat large cell lymphoma, generally, that’s not survivable.

But as I’ve also mentioned for at least 60 percent of patients and potentially even more, we can cure it with standard treatment. There are other types of lymphoma, such as indolent B-cell lymphomas where actually the goal is not cure, but patients may actually have a normal life expectancy meaning they will face multiple treatment courses over their lifetime. But at the end of the day, they should live just as long as someone their same age and sex who doesn’t have lymphoma.

So, again, that’s going to be a vastly different treatment course and outcome. So, sometimes, when you’re sitting in the waiting room and you’re sharing your journey with others, you have to keep in mind that you may all be using the same term, Non Hodgkin lymphoma. But our expectations in terms of treatments and outcomes might be vastly different. 

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.

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

What Are the Subtypes of DLBCL?

How Does Your DLBCL Subtype Impact Your Treatment Options?

Expert Advice for Newly Diagnosed DLBCL Patients

Expert Advice for Newly Diagnosed DLBCL Patients


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.

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

 

 

 
 

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

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

DLBCL Patient First Office Visit

Should DLBCL Patients Consider a Second Opinion?


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.

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

How Does Your DLBCL Subtype Impact Your Treatment Options?

 

 
Is COVID-19 Vaccination Safe and Effective for DLBCL Patients

 

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.

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

How Does Your DLBCL Subtype Impact Your Treatment Options?

 

 

 

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.

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

What Are the Subtypes of DLBCL?

DLBCL Treatment Decisions: What’s Right for You?


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.

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

DLBCL Treatment Decisions: What’s Right for You?

How Does Your DLBCL Subtype Impact Your Treatment Options?

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


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. 

DLBCL Treatment Decisions: What’s Right For You Resource Guide

Download Guide

PEN-144_DLBCL_ResourceGuide_F

Download Guide

DLBCL Treatment Decisions: What’s Right for You?

DLBCL Treatment Decisions: What’s Right for You? from Patient Empowerment Network on Vimeo.

When considering therapy for diffuse large b-cell lymphoma (DLBCL), what determines the best treatment for YOU? Lymphoma expert Dr. Loretta Nastoupil shares key decision-making factors, emerging research, and tools for partnering with your healthcare team.

Dr. Loretta Nastoupil is the Director of the Lymphoma Outcomes Database and Section Chief of New Drug Development in the Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Nastoupil here.

Download Program Guide

See More From The Pro-Active DLBCL Patient Toolkit


Related Programs:

DLBCL Patient First Office Visit


Transcript:

Katherine:

All right. Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re going to discuss how you can be proactive in your DLBCL care and work with your healthcare team to find the best treatment path for you.

Before we meet our guest, let’s review a few important details. The reminder email you received about this program contains a link to program materials. If you haven’t already, click that link to access information to follow along during this webinar.

At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars.

Finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please, refer to your healthcare team about what might be best for you.

All right. Let’s find out who we’re talking to today. Joining me is Dr. Loretta Nastoupil. Thank you so much for coming on the show with us. Would you please introduce yourself?

Dr. Nastoupil:

Sure. Thanks, Katherine. I’m Loretta Nastoupil. I’m in the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center. I’ve been here since 2013, and I currently lead our new drug development team in our lymphoma section.

Katherine:

Thank you so much for taking time out of your busy schedule to join us. 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.

Katherine:

Let’s look into testing for a moment. What tests are essential when making a diagnosis?

Dr. Nastoupil:

So, at the beginning, we clearly have to have tissue. I always say, “Tissue is the issue.” So, we may have features that are suggestive of lymphoma. And even sometimes radiologists will describe a CT scan or an x-ray and say, “This looks very suspicious for lymphoma.” But unless we actually have a biopsy that confirms lymphoma, we won’t go as far as to render a diagnosis in the absence of a biopsy.

Now our biopsy approaches have evolved over the last few years. The gold standard or what I would consider to be the best approach currently is to actually have an incisional biopsy meaning we find a lymph node that looks suspicious.

And we either remove the entire lymph node or a large section of that lymph node to render a diagnosis because there’s various things we need to do to that lymph node.

So, generally, we do what’s called immunohistochemistry staining. So, we stain either surface markers of those cells or markers within the cell because cancer is defined as having an abnormal clone or a population of cells that all have the same features. And they’re able to survive even if the host is not thriving.

So, that’s, essentially, what we’re trying to define. Are there cells in this lymph node that are all the same? And what features do they share in common? And then we will also do something called flow cytometry where we’ll take these cells and essentially sort them according to those surface markers. And that will also tell us – is this a B-cell clone, a T-cell clone, and what features would distinguish one lymphoma from another?

And the last thing that we need tissue for are what we call molecular studies, where we may learn about either genes that are rearranged or mutated within those cells that, again, may help us further classify the lymphoma and, again, group them into higher or potentially lower risk groups.

Katherine:

What do the results of these tests tell us about prognosis and treatment choices?

Dr. Nastoupil:

So, again, everything kind of hinges on what type of lymphoma we’re facing. So, for instance, diffuse large B-cell lymphoma is what we call an aggressive lymphoma. So, what does that mean? It can grow very quickly. It can take over the patient in terms of resources. So, generally, patients will have weight loss and sometimes even constitutional symptoms or B symptoms, such as night sweats and fevers, fatigue.

In the absence of treatment, it is universally fatal. Now, that timeline can vary from one person to another. But, generally, within a year, if we don’t treat large cell lymphoma, generally, that’s not survivable.

But as I’ve also mentioned for at least 60 percent of patients and potentially even more, we can cure it with standard treatment. There are other types of lymphoma, such as indolent B-cell lymphomas where actually the goal is not cure, but patients may actually have a normal life expectancy meaning they will face multiple treatment courses over their lifetime. But at the end of the day, they should live just as long as someone their same age and sex who doesn’t have lymphoma.

So, again, that’s gonna be a vastly different treatment course and outcome. So, sometimes, when you’re sitting in the waiting room and you’re sharing your journey with others, you have to keep in mind that you may all be using the same term, non-Hodgkin lymphoma. But our expectations in terms of to and outcomes might be vastly different.

Katherine:

From person to person. What are the stages of DLBCL?

Dr. Nastoupil:

So, we currently use what’s called the Ann Arbor staging system. And, again, this is very different from the staging applied in solid tumors.

And so, the way we define stage is based off where the tumor is in relationship to the diaphragm. So, if you have the disease just in lymph nodes and it’s all confined to one side of the diaphragm, it’s either gonna be stage one or two. And how we distinguish between one or two is just really not are they in close proximity and something that we would fit in one radiation field.

If you have disease that’s above and below the diaphragm, that’s generally at least Stage 3. Stage 4 is generally when it’s now outside of the lymph node. So, what we call extranodal location. So, those are generally organs, lung, liver, skin, bone, etcetera.

It can be very complicated in that you could have just one extranodal site. So, say you just have stomach involvement, or you just have one area of the bone. That could be a 1E.

So, it’s important to recognize every patient has a stage. What that means is whether or not we would give a full course of therapy in terms of systemic treatment that goes through the vein or maybe a shortened course in radiation is dependent on that stage.

Katherine:

Now that we understand a bit more about DLBCL and how it’s staged, let’s move on to treatment options. Many factors come in to play when making a treatment decision, including a patient’s age and overall health. So, let’s walk through some of these considerations. Let’s start with treatment goals. What does this mean exactly? And what are the goals of treatment for DLBCL?

Dr. Nastoupil:

Great questions. For diffuse large B-cell lymphoma, my goal was that I want to eradicate this disease with one course of therapy. Now one course of therapy, again, may mean six cycles of treatment, or it may mean three to four plus/minus radiation. And that kind of gets back to the discussion we just had with stage. But the goal is to make it go away and never come back. Now, oncologists are eternal optimists.

And I saw this because we would not be oncologists if we weren’t always focused and hoping for the best outcomes for our patients.

Katherine:

Sure.

Dr. Nastoupil:

So, we, generally, when we’re counseling patients tend to keep the focus on what is the chance that I can cure this, and we use words like cure oftentimes. But there’s always those caveats. And those caveats are – we can’t really look into our crystal ball and predict the future for every given patient. So, we use tools to help us risk stratify patients, meaning if we took 100 people like a given person, we could predict the outcome for the majority of those patients.

So, with diffuse large B-cell lymphoma with no high-risk features – so, that gets back to the molecular subtype. Do they have double hit features – yes or no? The stage and something we call IPI, International Prognostic Index, that takes into account some clinical features. As you mentioned, patient specific factors, their age, their stage, some lab values, whether or not they have more than one extranodal variable. Then we can generally predict.

Again, if I have 100 patients with good risk IPI, 80 percent of them are likely to be cured and alive and well five to 10 years later. If I have someone with poor risk features that may not change exactly what I do for that patient, but that may help them and me in terms of should I be pursuing a trial to potentially have access to something that’s better than this standard option? Or how does this impact their planning?

Some people are close to retirement. Some people have specific life goals, such as a wedding or an anniversary that sometimes we use those sorts of calculators to best predict the future to inform some of that treatment. So, those are what we call sort of the characteristics coming into treatment.

There are comorbidities or sort of concomitant medical problems, such as heart disease, sometimes diabetes. But, generally, more often than not, it’s how healthy your heart is because my objective with treatment is to cure this.

Cure generally results from chemotherapy. And we can spend some time talking about why have we not moved away from chemotherapy in this disease? But, generally, that does involve chemo because that’s generally how I can eradicate this tumor.

But there are certain situations where that chemo may not be beneficial to a given a patient. It usually has to do with how healthy their heart function is at baseline. So, again, we look at all of these factors. What is their risk with the disease? What is their risk from the toxicity of treatment? And am I able to achieve that goal, which is to eradicate the disease?

Katherine: Well, let’s talk about chemotherapy. Why is that still part of the regimen in a treatment plan?

Dr. Nastoupil:

Yes, I’m gonna borrow an analogy that one of my colleagues Jason Westin uses all the time. The CHOP chemotherapy that is the backbone of our treatment for diffuse large B-cell lymphoma was developed in 1976.

There is no other technology that we would commonly use in our day to day. You wouldn’t still be driving your car you had in 1976. Clearly, our methods of communication in regards to phones have changed dramatically. So, why are we still using chemotherapy that was developed in 1976?

Katherine:

True.

Dr. Nastoupil:

Well, it’s not for lack of trying. Over the last four or five decades, we have been trying to improve upon this. And it works. It works for at least 60 percent of patients. When we tack on targeted therapy, such as immune therapy where we use an antibody that will stick to the surface of a marker on that lymphoma cell and then use the immune system to do some of the heavy lifting, we can probably improve those cure rates from 60 percent to potentially as high as 80 percent. That’s really been the only substantial improvement we’ve made.

Now, there is one caveat. So, just recently, we heard a press release of the POLARIX study, which is the first trial in the last four decades that could potentially replace R-CHOP as the standard of care.

We don’t have the full results yet. It’s essentially utilizing a drug called polatuzumab, which is an antibody drug conjugate. It’s essentially chemo on a stick. But we’re delivering chemo specifically to (CD)79b, which is a target on B cell lymphomas and modifying the CHOPs. We’re not getting rid of chemo altogether. We’re dropping one of the chemotherapy agents and replacing it with this targeted agent. So, it’s essentially CHP plus rituximab and polatuzumab might be the new standard.

But, again, that’s based off many, many efforts to try and replace CHOP. And we’re making slow incremental improvements, but we’re still keeping the therapies that tend to work.

Katherine:

And that makes sense. 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 BCL2 or BCL6. 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 gonna 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.

Katherine:

Exactly. Does treatment typically start right away?

Dr. Nastoupil:

Hopefully. So, what I mean by that is everyone has to have a diagnosis. And a common story that I hear is that patients generally know when they’re not doing well. They may not be able to pinpoint I have lymphoma.

But they usually will see a primary care doctor or depending on the location of a lymph node if it’s palpable. Oftentimes, men when they’re shaving will pick up a lymph node in the neck. Or women if they’re having a mammogram will pick up a lymph node in the axillae or under the arm. So, that may lead to further investigation based off the location of a lymph node.

Or it may just be those constitutional symptoms where people aren’t feeling well, and a primary care doctor is their first stop. Lymphoma is rare. So, usually it’s a diagnosis of exclusion or something that we eventually get around to. That is important, but it’s not that important.

So, what I mean by that is I hope patients don’t have any guilt or regret if they’ve been sitting on symptoms for a while or even if their primary care doctor missed signs and symptoms of lymphoma because, again, it’s not very specific. There are a lot of things that can cause similar presentations.

But once we have imaging that is suggestive of lymphoma and then we have a diagnosis that’s rendered, again, followed by a biopsy, generally, then it is important that they seek care.

And they get that care in a timely fashion. What’s kind of interesting is the longer time from diagnosis to the initiation of treatment in diffuse large B-cell lymphoma is usually associated with a better prognosis. So, that’s sort of counterintuitive.

One would think that the sooner you get started on treatment, the better your outcome will be. I think the challenge with interpreting that data is that the longer time from diagnosis to initiation of treatment usually means that that patient’s disease is one that lends itself to the affordability of time to be seen by specialists, have all of your staging studies completed, have a return visit to go over all those results and have a shared decision-making process in terms of deciding what’s the best treatment for you, and then getting started on that treatment.

So, those patients where that is agreeable and acceptable, they’re probably gonna do very well.

For the patients who are really sick and they need to get started on treatment sooner rather later as a result of their disease putting them at risk, either as a result of organs not functioning well or substantial symptom burden as a result of their disease, then they need to get started. So, that’s usually why their course from diagnosis to treatment is generally shorter.

So, again, it all kind of depends on a given situation. But with diffuse large B-cell lymphoma, I tell patients usually within three months of knowing you have lymphoma, we need to get you on treatment, or you’re gonna be sick.

Katherine:

I can imagine. You touched on this a few moments ago. But what do you feel is the patient’s role in this whole decision?

Dr. Nastoupil:

So, I’ve actually been a patient myself, and I have mixed feelings about it. I think oftentimes as an oncologist, we share decision-making when we don’t know the exact path forward, meaning if there’s something controversial or you have more than one option, generally, we kind of put out all the information to the patient, and we want you to be part of that decision-making.

And I think that’s important because we’re all humans, and we all want liberties. And we want our patient rights to be acknowledged and respected. And that’s important. I think sometimes though that also burdens patients with making decisions when they may feel they don’t have all of the information to make an informed decision.

But your role as the patient is you know your body better than anyone. And, generally, if there’s something that just doesn’t fit well or sit well with you, be vocal about it. So, I’ve been in a situation where I felt like I had to speak up a few times, and not that I have all the answers. And I am an oncologist. So, I generally have more insight than others.

But, generally, I was right in that, again, I think we know our own bodies. And when you feel that something is being missed or maybe not given the time and attention it deserves, speak up. You also have a role in making sure that the diagnosis is correct.

So, I generally advise all patients because everything hinges on the diagnosis in lymphoma, more so than the staging, more so than sometimes even the treatment itself.

Getting a second opinion can be incredibly valuable because you have another pathologist that will lay eyes on this biopsy. And lymphoma is rare. So, a second opinion can be incredibly valuable, and that’s usually something driven by a patient more so than an oncologist. Though some oncologists – and I would say the majority – are open to an opinion because they too would like information or confirmation that they’re on the right path.

Katherine:

Certainly.

Dr. Nastoupil:

The other thing that I think patients can have role is exploring what trial options are out there and available to them. I think that is sometimes a tough subject to discuss. Clinical trials are not only for patients who have failed all the standard treatments.

And it’s usually not an option of hospice versus a clinical trial. That’s absolutely an inappropriate time to consider a clinical trial. And, generally, there are trials at any point in a patient’s journey where there is some controversy as to the best path forward.

Again, I’ve been discussing the last 40 years of trying to improve upon R-CHOP is because 60 percent of patients were cured, but 40 percent were not. There is always a scenario where we could do better. And, generally, the only way we will improve upon outcomes is to conduct important rational clinical trials.

So, sometimes, it’s as simple as reaching out, participating in programs such as this, reaching out to the Lymphoma & Leukemia society or the Lymphoma Research Foundation to just explore what are your trial options. They may not be appropriate for you right now but at least understanding where there is an opportunity to participate in a trial is worth exploring.

Dr. Nastoupil:

Dr. Nastoupil, now that we’ve discussed factors that go into the treatment choices, can you walk us through the currently available DLBCL treatment approaches and who they might be right for?

Dr. Nastoupil:

Absolutely. So, again, this is changing, and that’s good news. So, up until recently, R-CHOP or rituximab in combination with CHOP, which is an acronym for four different drugs, cyclophosphamide, doxorubicin, vincristine, and prednisone, has been our standard.

Again, what would potentially challenge that is the POLARIX study where we exchange vincristine for polatuzumab. We don’t know the results of that study yet. All we know is that it met its primary endpoint, meaning it met what it set out to do in terms of improving upon some of the outcomes achieved with R-CHOP.

We need to see the details to know if that means now every newly diagnosed diffuse large B-cell lymphoma patient will be offered the polatuzumab in combination with R-CHP study or whether or not there will still be some patients appropriate for R-CHOP.

But that is generally our first approach. Whether you get six cycles or a shortened course plus/minus radiation depends on your state. Once patients have completed therapy, generally, then we pursue what’s called surveillance.

So, we’re monitoring for any signs that the lymphoma has recurred or has not gone away. That’s a controversial topic in terms of how to conduct surveillance and one that I suspect will change over time. But for most patients, if the lymphoma is going to recur, it generally recurs within the first two years.

So, assessing patients either in the form of a CT scan, a PET CT, or a physical exam with labs every four to six months for the first two years is what most practices will pursue. I’m not saying that there is no chance that you would relapse beyond two years. It’s just that the majority of patients, at least 90 percent, if the lymphoma comes back, it usually does so within two years.

And the relapses that occur beyond two years are less predictable. They could happen at three years. They could happen at 10 years, as it’s hard to know how to do surveillance beyond two years.

If the lymphoma recurs, the first thing we need to do is biopsy it because there are many things that can mimic lymphoma on a scan – infection, inflammation, other tumor types. So, if there is ever a question about whether or not the lymphoma has recurred, I generally advise for all patients they undergo a biopsy to ensure that we know what we’re treating.

Depending on when the lymphoma recurs, if it happens within 12 months, this is another area that we are shifting our practice. In the past, for all patients who had relapsed large cell lymphoma, we would pursue what we call salvage or second-line chemotherapy. So, we mix up the chemo. We keep, generally, the rituximab, but we alter the chemotherapy agents. We wouldn’t give CHOP again.

And then we give a shortened course where we give two to three cycles. We repeat the scan. And for patients who’ve achieved what we call chemo-sensitive disease – so, that’s generally a complete response on scan – we would then move forward with high-dose therapy and an autologous stem cell transplant. So, essentially giving different but more intense chemo and rescuing patients from that maneuver with their own stem cells that will go back to the bone marrow and start making white blood cells, red cells, and platelets again.

What has shifted in the last six months is we now know that CAR T-cell therapy is superior to that approach, at least with two CAR Ts for patients whose lymphoma came back within 12 months. Again, we’re eagerly awaiting the full results of those randomized studies. But three trials were conducted. Two of the three suggest CAR T is better than second chemo and transplant for those patients who relapse within 12 months.

So, currently, we think that you’ll have a CHOP-like therapy with plus rituximab frontline. If you progress within 12 months, you potentially would be a candidate for CAR T-cell therapy. If the CAR T-cell therapy fails, which is true for about half of patients, or if you’re deemed to not be a candidate for CAR T, we have several other new options that didn’t exist a year ago, including targeted or non-chemotherapy options.

So, there are at least four options in that setting now that are therapies that target the lymphoma cells, either by targeting CD19, which is another surface marker, augmenting that either with an antibody drug conjugate, such as Lonca, or with an immune therapy, such as lenalidomide and tafasitamab. Polatuzumab is available in that third line or later space combined with bendamustine and rituximab. There’s an oral agent called Selinexor.

So, a lot of that is not to burden patients with information but to let them know they’ve got lots of options. And many of these can be sequenced. So, if we can’t achieve cure with R-CHOP and/or CAR T, there are still very good outcomes in that third line or later space.

Katherine:

We’ve covered a lot of information here so far. And just a reminder that the resource guide I mentioned earlier contains definitions and resources for what we’re discussing today. So, be sure to click on that link if you haven’t already.

Dr. Nastoupil, I’m wondering how patients can feel confident in speaking up and becoming a partner in their care.

Dr. Nastoupil:

So, it’s important to recognize, and I reflect on this all the time. Generally, once patients have been rendered a diagnosis of cancer, that’s a life-altering event. And even if I spend a lot of time trying to reassure patients that outcomes for lymphoma patients are very good, generally we’re aiming for cure, that’s not true for everyone.

And you can’t help but be concerned that you will succumb to this disease or that the toxicity of therapy is gonna be life-altering and impact your quality of life in such a way that it’s no longer the life that you were happy to live.

And so, I recognize that we are partners in this. My job is to choose the most effective therapy that will try and accomplish the goals we set out to achieve. However, sometimes, oncologists make assumptions about what the goal of a given patient is.

We’re assuming that longevity or living is the most important goal. Whereas sometimes, people might care more about the quality of life, or they may need more reassurances about what the options are or their realistic outcomes with therapy. Because, again, I’ve mentioned before, oncologists are generally eternal optimists. We tend to sugarcoat things a little bit.
So, it’s important for patients to recognize that they will have a shared decision responsibility, meaning oftentimes we will provide all the information that we have access to in terms of a given treatment.
What is the likelihood of success, what is the potential risk in terms of toxicity, and what we’re leaning towards one therapy over another, particularly if you have more than one option.
But, ultimately, we need patients to share with us what their goals are in terms of outcome of that treatment so that we can then potentially refine our treatment selection. So, again, being informed, participating in programs like this so that you understand what makes one lymphoma different from another. Why would one oncologist offer one treatment and another discuss something else?

So, understanding what the different lymphomas are, how they might be approached differently, what the new therapies are. I struggle to keep up with just the lymphoma literature and changes. I can’t imagine what it must be like for an oncologist that treats every cancer type. So, again, understanding that new drugs are approved almost every couple of months in lymphoma may provide an opportunity for patients to share new information with their oncologists as well. So, information is key.

Katherine:

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

Dr. Nastoupil:

Well, I appreciate your time as well.

Katherine:

And thank you to all of our partners.

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

DLBCL Care Partner Follow-Up Office Visit Planner

Download Planner

PEN-144_Caregiver_Follow-Up-Visit-Planner_F

Download Planner

 

DLBCL Care Partner First Office Visit Planner

Download Planner

PEN-144_Caregiver_First-Office-Visit-Planner_F

Download Planner