Tag Archive for: DLBCL clinical trials

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

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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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Why Should DLBCL Patients Feel Empowered to Speak Up?

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Why Should DLBCL Patients Feel Empowered to Speak Up? from Patient Empowerment Network on Vimeo.

Why is it vital for diffuse large B-cell lymphoma (DLBCL) patients to engage in their care? Expert Dr. Amitkumar explains the importance of speaking up and the value of considering a second opinion.

Dr. Amitkumar Mehta is Director of the Lymphoma Program and CAR T Program and Medical Director of the Clinical Trials Office at O’Neal Comprehensive Cancer Center at UAB. Learn more about Dr. Mehta.

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How Can DLBCL Patients Benefit From Shared Decision-Making?

Transcript:

Katherine:

Why should patients feel empowered to speak up?

Dr. Mehta:

So, that is very, very important because at the end, anybody and the patient is in the center. As we talked about their preferences, shared decision-making, they need to speak up because, at the end, I need to know, we need to know as a care team their preferences, right? Who is going to be my support? Who’s going to be with me? Maybe they might have to move somewhere to get the treatment, right? Or sometimes I bring up and I have so many patients who actually brought up “Well, I have a trip planned on this date,” right, or “I have a graduation planned,” or “I have son or daughter’s wedding planned,” right?

So, they should feel empowered to speak up. Yes, they’re shocked at the first instance because of their diagnosis of cancer. But that part after sharing all the information about cancer and treatment, it eases up a little bit. Then they feel “Okay, it is not end of the road,” right? “I’m going to fight it out.” But at the same time, there are important life events planned. So, they need to speak up, not only for that but also, as we talked about, preferences, their choices about the clinical trial.

Sometimes it is okay to ask whether I can go for another opinion, especially now in many institutions there are specialists who just focus on lymphomas, right? In that case, it is okay to ask whether – anywhere else I should go for an opinion and see whether I have more options. So, patient is always in center. And I feel always comfortable when patients speak up, and I make sure that “Yes, I will make sure that whatever the preference is, I will try to meet those preferences.”

How Can DLBCL Patients Benefit From Shared Decision-Making?

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How Can DLBCL Patients Benefit From Shared Decision-Making? from Patient Empowerment Network on Vimeo.

What is shared decision-making, and how can it help diffuse large B-cell lymphoma (DLBCL) patients? Expert Dr. Amitkumar Mehta explains the process and shares key questions to ask about treatment and care. 

Dr. Amitkumar Mehta is Director of the Lymphoma Program and CAR T Program and Medical Director of the Clinical Trials Office at O’Neal Comprehensive Cancer Center at UAB. Learn more about Dr. Mehta.

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 Why Should DLBCL Patients Feel Empowered to Speak Up

Why Should DLBCL Patients Feel Empowered to Speak Up?

Transcript:

Katherine:

What is shared decision-making, and how does it work?

Dr. Mehta:

Shared decision-making has evolved over the last couple of decades.

And exactly as we were talking about the treatment, this is – I always share with my patient that we are on your side, right? We are with you. We are part of your journey. And, of course, for anyone, this could be a brand-new journey, right? So, each person is different. Each person’s preference is different, right? In that case, when I have the details of whether it’s lymphoma or treatment, they also have input. They might have read somewhere. They might have a family member who had gone through the chemotherapy, and they have preferences, let’s say.

So, when we sit down and discuss that time, they also have an input on that. Write appropriate questions, you know. What is my diagnosis? What stage it is, right, whether it’s high risk or low risk? What are the potential for cure, right? What kind of chemotherapy you’re looking at, whether I have more options in that like clinical trial, right?

Yes, you said you were going to treat me with standard of care. Do I have an option of clinical trial? Like in DLBCL setting, R-CHOP, or R-EPOCH, which is the foundation of DLBCL treatment for so long. What is happening in the clinical trial is we are building on that foundation. We are building on the standard of care. So, there could be a potential that you are an eligible patient for X, Y, Z clinical trial, where you’re getting an added novel immunotherapy drug or a bispecific antibody.

Why you’re doing that to see whether we can improve upon whatever we have. So, in that, if patient is informed, they can also be a part of the conversation, right? It is just like when we go for, say, buying a car. It is not that a dealer is showing us a car, and we say, “Okay, I’ll go with it.” No, we say, “What color it is? I want this color. I want this seat. I want this model.”

I mean, that is a shared decision-making, right? And then we come to a conclusion. “Okay, this is the car that I prefer, I’m comfortable with, and I’m going to buy that.” It’s similar in cancer care.

How Can You Access DLBCL Clinical Trials?

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How Can You Access DLBCL Clinical Trials? from Patient Empowerment Network on Vimeo.

Where do clinical trials fit into a DLBCL treatment plan? Dr. Jason Westin explains the importance of trials and discusses how patients can learn more.

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:                  

You touched upon clinical trials. Where do they fit in?

Dr. Westin:                 

Yeah. In my view, clinical trials are our best weapon against cancer, period. I think that’s true across the board, even for cancers like DLBCL where the majority of patients are cured with their first treatment, like an R-CHOP type therapy. All of our treatments at some level came from a clinical trial. They didn’t just have treatments fall out of the cancer treatment tree. They all came from patients going on to clinical trials, trying to improve upon previous standards.

And as I mentioned, CHOP has been there for about 40 years. R-CHOP has been there for about 20 years. We don’t do a lot of things that we would consider risk of death that we trust a 40-year-old technology to try and save us from. We like the latest, we like the modern, we like what’s the shiny new object. And so, clinical trials are the way that we define new standards and move forward to do new therapies.

CAR T-cells are an incredible advance. Those didn’t exist a handful of years ago. They were only defined as successful in clinical trials. So, my advice to a patient who is diagnosed with DLBCL is ask your provider, as your physician, or your PA, or your nurse practitioner, “What clinical trials are available to me?” If the answer is, “We don’t have any,” go on the internet and figure out where you can go for a second opinion where clinical trials might be available. And there are plenty or resources online to try and figure this out.

Time is of the essence for this DLBCL. We don’t have six months to shop around and go figure out what centers, but clinical trials are really the only engine we have to drive progress to do better and cure more patients.

The Benefits of Having a Role in Your DLBCL Treatment Decisions

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The Benefits of Having a Role in Your DLBCL Treatment Decisions from Patient Empowerment Network on Vimeo.

Diffuse large B-cell lymphoma (DLBCL) patients have a vital role in their treatment decisions. Expert Dr. Loretta Nastoupil shares advice for patients on how to advocate for their best care, the value of a second opinion, and credible resources to boost knowledge about DLBCL.

Diffuse large B-cell lymphoma (DLBCL) patients have a vital role in their treatment decisions. Expert Dr. Loretta Nastoupil shares advice for patients on how to advocate for their best care, the value of a second opinion, and credible resources to boost knowledge about DLBCL.

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Transcript:

Katherine:

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.

Katherine:

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 going to 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. 

What Are the Goals of DLBCL Treatment?

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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.

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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. 

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

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

How is diffuse large B-cell lymphoma (DLBCL) treated? Dr. Jean Koff shares insight about DLBCL treatment types, factors to consider in determining treatment options, reviews approaches for relapsed disease, and explains the role of clinical trials.

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:

In general, then Dr. Koff, how is DLBCL treated?

Dr. Koff:

So, in general for patients who are getting their first-line therapy, they will receive some sort of combination of chemotherapy and what we call immunotherapy. For the vast majority of patients who are young and otherwise, healthy this will be a combination chemotherapy regimen known as R-CHOP.

Which consists of three what I call conventional chemotherapy drugs, an immunotherapy called cyclophosphamide and a steroid known as prednisone.

Katherine Banwell:

What are the main factors you take into consideration before a treatment approaches decided on? You mentioned age, health.

Dr. Koff:

Yes. So, I divide it into three different categories. The first category is the patient. So, there are patient factors that determine what treatments the patient is able to tolerate. And some of the main factors you mentioned are items like age or what we call co-morbidities, which are other health problems that the patient may have. But there may be other factors as well.

If a patient is not able to take care of themselves very well, because they’re very ill or they’re very debilitated or they’re unable to receive certain treatments because they have social factors that keep them from coming to certain centers or from following-up with care. Those all fall under that patient-centered bracket.

The next factor that I consider are items related to the lymphoma itself. So, we’ve already mentioned factors like, expression of different genes or having certain gene abnormalities. Those may play a role in determining what treatment a patient gets. And then, the last big category is where the lymphoma is in the body. And this refers, generally if the lymphoma is only in one limited site. Then those patients may get fewer cycles of chemotherapy, less time in chemotherapy and may receive radiation as part of their frontline treatment.

Whereas patients who have disease in more than one site who are spread out across the body, make it more cycles of chemotherapy. But also there are patients who have lymphoma in certain sites that requires that we give additional treatment to make sure that the disease in those special sites is treated

Katherine Banwell:

Where do clinical trials fit in, Dr. Koff?

Dr. Koff:

So, our goal in treating diffuse Large B-cell lymphoma in the first-line setting in somebody who’s newly diagnosed in most patients, our goal is to cure. Meaning that we treat the patient with chemo immunotherapy. And our goal is that the lymphoma never comes back, goes away and never comes back. Unfortunately, as of today we’re not able to cure every single patient. And depending on what factors you have in your disease, your likelihood that you will be cured with that first-line therapy may be higher or lower.

But until we’re able to cure every single patient with our first-line therapy, there is definitely room for improvement. And that’s where clinical trials feature in. Because the way that we are able to tell whether new therapies or new approaches to therapies are improving upon our goal of curing or our goal of controlling the lymphoma. We need to test them very rigorously in clinical trials.

Katherine Banwell:

Of course. Now what about for patients with relapsed disease?

Dr. Koff:

So, there are several different approaches that we use to patients who have relapsed depending on a lot of different factors that may play into a particular case. I would argue that in this case, clinical trials are even more important.

Because although we can still treat with the goal of cure for a relapsed patients with DLBCL, the likelihood that somebody will be cured after they’ve received their frontline therapy goes down, regardless of the factors related to the case. And so, this is a setting where it’s even more important that we improve upon our current strategies of treatment and our current treatments that we have available in clinical trials again are the way that we move forward with this.