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. 

Is COVID-19 Vaccination Safe and Effective for DLBCL Patients?

Is COVID-19 Vaccination Safe and Effective for DLBCL Patients? from Patient Empowerment Network on Vimeo.

Is COVID-19 vaccination safe and effective for diffuse large B-cell lymphoma (DLBCL) patients? Dr. Jean Koff shares what’s currently known about COVID-19 vaccination for DLBCL patients and provides information about studies currently underway on immunocompromised patients.

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:

A question that’s on many people’s minds right now is if the COVID 19 vaccination is safe and effective for people with DLBCL? 

Dr. Koff:

So, I don’t think we have any reason to believe that it’s not safe. We haven’t seen any signals that it is not safe. I think there are reasonable concerns that for patients who either have active lymphoma where the lymphoma may be impacting their immune system and the immune system’s ability to mount the response that you need to get immunity when you get vaccinated. But even more so patients who are receiving some sort of therapy, especially chemotherapy and immunotherapy. Those types of treatments actually may knock out the same normal bystander immune cells that help you mount that immune response when you get vaccinated.   

And so, the concern there is that in those individuals either with active DLBCL or who are receiving treatment for DLBCL, that their immune systems might be somewhat compromised and not able to mount as robust of an immune response when they get vaccinated. 

And by extension, the vaccine may not work as well to protect them against COVID as it would in somebody who doesn’t have a compromised immune system. But what I’m counseling my patients is that if they are not actively receiving treatment that impacts their immune system like chemo or immunotherapy, I am recommending that they go ahead and get the vaccine.  Because to me the risk of COVID and COVID-related complications is very high. And the risk of complications from the vaccination is very low. And the protection that it offers – while we are not sure the level of protection that it offers in these special cases, some protection, if it does offer it is better than no protection. And the risk of immunization is low. We are actually doing the studies now at Emory.  

In specifically lymphoma patients who get the COVID vaccine. Whether they have active lymphoma or getting treatment in lymphoma, we’re doing the studies now to take a look and see whether they’re able to adequately mount immune responses to the COVID vaccine. So, that we can better counsel our patients on how effective these vaccines will be.   

So, once we have more mature data from our studies and from other centers, similar studies, we’ll be able to better estimate what the chances that the vaccine will be protective for an individual patient.

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.

See More From The Pro-Active DLBCL Patient Toolkit


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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.