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Clinical Trials as a Prostate Cancer Treatment Option | What You Should Know

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Clinical Trials as a Prostate Cancer Treatment Option | What You Should Know from Patient Empowerment Network on Vimeo.

Should you consider participating in a prostate cancer clinical trial? Dr. Sumit Subudhi explains the clinical trial process, addresses common trial patient concerns, and provides key advice for trial participation. Dr. Subudhi also shares an update on promising prostate cancer research.

Dr. Sumit Subudhi is an Associate Professor in the Department of Genitourinary Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center.

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Transcript:

Katherine Banwell:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss prostate cancer research advances and the role of clinical trials and moving treatment developments forward. Before we meet our guest, let’s review a few important details.   

The reminder email you received about this program contains a link to a program resource guide. 

If you haven’t already, click that link to access information to follow along during the webinar. At the end of this program, you will receive a link to a program survey. This will allow you to provide feedback about your experience today, and it will 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. 

Well, let’s meet our guest today. Joining me is Dr. Sumit Subudhi. Dr. Subudhi, thanks for being with us. Would you introduce yourself? 

Dr. Subudhi:

Hi. I’m Sumit Subudhi. I’m an associate professor in the GU Medical Oncology department at MD Anderson Cancer Center. And I exclusively treat patients with advanced prostate cancer. And I’ve been doing it for about a decade. 

Katherine:

Thank you. I’d like to begin with an update on prostate cancer research. Would you walk us through the newer classes of treatments that are showing promise? 

Dr. Subudhi:

Yeah, in clinical trials, there are classes of drugs known as androgen receptor degraders. And so, the androgen receptor is a protein that basically is the mouth of the prostate cancer. That’s how I like to describe it. And it actually allows testosterone, which is the food, to be eaten by the mouth, and it actually helps the cancer grow. 

And what these drugs do is they actually degrade or break down the mouth of the cancer. And, therefore, it starves the cancer to death, and that’s actually the concept. And they seem to be showing some exciting activity in clinical trials, especially in those patients who are resistant to the second-generation hormonal drug that you may have heard of already, such as enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). So, I think is something that we’re looking forward to seeing more data on. 

Another class of drugs are antibody drug conjugates or ADCs.  

And these are what I think of as heat-seeking missiles. So, one part of the drug actually recognizes the cancer, and the other part of the drug actually has a payload that sort of releases a bomb or sort of like chemotherapy-type agent right where the cancer’s located and kills the cancer in that way. And we’re seeing some great clinical activity in prostate cancer with this class of drugs. 

And then the final one is bispecifics, and in particular T-cell bispecifics. So, T cells are part of the immune system that actually help kill the cancer.  

And, unfortunately, prostate cancer, like some other cancers like pancreatic and glioblastoma, have few T cells inside it. And, therefore, a lot of the immunotherapies that many people have heard about, such as ipilimumab (Yervoy) and pembrolizumab (Keytruda), they’re not very responsive in patients with prostate cancer. And it’s because there’s few T cells in prostate cancer.  

What the T-cell bispecifics do is they actually have one part of the drug that actually recognizes the cancer and the other part that recognizes T cells. So, like a bulldozer, it brings T cells right into the prostate cancer and helps kill the cancer that way.  

Katherine:

Now there are some inhibitors as well. Is that correct? 

Dr. Subudhi:

Yeah. So, the immune checkpoint inhibitors have been around for a while. And, basically, in combination, they seem to be more effective in prostate cancer. But when given alone as monotherapy, they’re less effective. 

Katherine:

Are these treatments specifically for patients with advanced prostate cancer? 

Dr. Subudhi:

All of them are actually in trials in patients with advanced prostate cancer. And I define advanced prostate cancer as either having metastatic disease, meaning the cancer has spread to other parts of the body outside of the prostate.  

Examples include lymph node, the bone, the lung, the liver. But there are so few trials in patients with locally advanced prostate cancer. What I mean by that is they have high-grade prostate cancer, but it’s local, or it’s just in regional lymph nodes. And some of these classes of drugs are being evaluated in that setting as well. 

Katherine:

Let’s shift to talk about your research. What are you excited about right now? 

Dr. Subudhi:

So, my research focuses on immune checkpoint therapies, which are the inhibitors that you were referring to and understanding how to make them work better in prostate cancer. 

And we’re finding out that in prostate cancer there’s about 20 to 25 percent of patients that appear to respond to this type of treatment. But these are patients that don’t have a lot of bone metastases. And these immune checkpoint inhibitors are given in combination. So, they’re not given alone. They’re given with either a combination of anti-CD34 and anti-PD-1 or some other form of that. 

Katherine:

Prostate cancer research really can only move forward through clinical trials and patient participation in those trials. Can you briefly explain what a trial is for people who may not be familiar with the term? 

Dr. Subudhi:

That’s a great question. My own father has prostate cancer. And he had the same exact question when he started his journey in that. 

And so, what I explained to him is that clinical trials are experiments. They’re experiments that are done in our patients.  

So, they’re drugs that are thought to mechanistically kill the cancer cell or at least change the environment around the cancer cell to help people live longer. But these drugs were actually tested in mouse models or in tissue models. And we don’t know if they actually work in patients. 

And so, in clinical trials, we’re actually testing whether these drugs are safe and whether they’re efficacious or beneficial to our patients. So, I want to be very clear. When patients go on clinical trials, we don’t know if it’s going to work on them. And that’s something that they should know that they’re showing a lot of courage and risk in joining these trials.  

But the other point I want to make is that every standard of care drug that is out there actually went through the clinical trial process, and they were approved because they showed benefit in a group of patients. 

Katherine:

Well, how can a prostate cancer patient benefit from participating in a trial? 

Dr. Subudhi:

One of the key benefits is that you get access to drugs that may actually prolong your life or even cure you and that you wouldn’t have access to in trials.  

And so, some of my patients, unfortunately, they’ve exhausted all the standard of care choices that are out there. And the trial’s the only option left versus leaving it up to natural causes of demise from prostate cancer. And so, clinical trials give other opportunities to potentially live longer and have a great quality of life. 

Katherine:

So, they could offer some hope. 

Dr. Subudhi:

Definitely. As far as I’m concerned, yes. And, actually, with my patients, I try to not wait while they’ve exhausted all the treatments to start them on clinical trials, because I feel like we may be able to save some of these treatments in our back pocket for when they’re too exhausted to be coming to our clinic so often. And so, I like to actually try to get them enrolled in clinical trials early on in their journey with prostate cancer. 

Katherine:

I’d like to define some clinical trial terminology to help patients further understand the process. Let’s start with the phases. What occurs during each phase?  

Dr. Subudhi:

So, great question. Phase I is the safety phase. So, all we’re trying to do is find the right dose of the drug that is actually safe to give in the patients. And we’re looking for the maximum tolerated dose. And once we find that dose, then we use that dose to go to Phase II of the trial. And Phase II trials are looking at efficacy. So, looking to see whether the trial is giving you any clinical benefit, meaning the cancer’s shrinking or even disappearing. 

Katherine:

Go on.  

Dr. Subudhi:

And then the third phase is Phase III where you’re testing the current drug, experimental drug, to either standard of care or to a placebo to see whether or not you get a benefit, either a progression-free survival benefit or overall survival benefit. And so, those are the three phases of clinical trials.   

Katherine:

What are the different types of clinical trials? 

Dr. Subudhi:

So, they’re controlled trials. Actually, I should back up. So, there’s open-label trials where everyone that enrolls in the trial will get the experimental drug. So, there is no control arms in these trials. Then there is the control trials where you can either get the drug, or you may get a placebo or standard of care drug.  

There are some trials that allow for crossover, meaning that if you’re in the placebo or standard of care arm, if your cancer progresses, you can actually cross over and get the experimental drug. But I just want to be clear that not all clinical trials have crossover. And if you’re in a control trial, I think that’s an important question to ask your doctors about that. 

But the reason why we do the control trials is that we’ve learned that using historical controls – for example, we’re doing a lot of combination studies with chemotherapy, such as docetaxel (Taxotere), which was FDA-approved in 2004. So, if we’re using historical data from almost 20 years ago, it’s not the same thing as our patients that are being treated with docetaxel now, because their treatment landscape has changed so much, and our patients have changed so much. 

And so, for that reason, control trials give us a better sense of how effective this experimental drug is doing as opposed to comparing it to a historical perspective. 

Katherine:

What other types of clinical trials are available? 

Dr. Subudhi:

So, there are a few other options. So, we talked about open-label where everyone’s guaranteed to get the drug. We talked about a controlled study where you will either get one drug or another. And another type is a randomized trial where a computer decides whether or not you’re going to actually get one drug versus another. It’s not your doctor because a lot of people think that I’m making that decision, and I’m not. It’s actually a random computer. 

And some trials have 1:1 ratio, meaning a 50 percent chance that you’ll get the experimental drug versus the control drug. But other trials have 1:2 ratio or 1:3 ratio. So, that’s something that, again, you have to ask your physician of how these trials are being randomized. 

Katherine:

Well, in a randomized clinical trial, the patient isn’t going to know what drug they’re being given. 

Dr. Subudhi:

Actually, that’s not true. 

Katherine:

Oh, it’s not. 

Dr. Subudhi:

So, you bring up a great question. So, there’s a double-blind randomized clinical trial where not only the patient doesn’t know, but even the physicians and the nurses. No one except for the pharmaceutical company that’s running the trial actually knows who’s actually getting which drug. And it’s only towards the end of the trial that we unblind, and then we share that information. Well, the pharmaceutical company first shares it with the medical team who then shares it with the patient. 

Katherine:

I see. Are there other common clinical trial terms that you think patients should know about and understand? 

Dr. Subudhi:

I think for now those are… 

Katherine:

…they’re the most important?  

Dr. Subudhi:

I think to me those are the most important. And I think that sometimes too much information can bog us down.  

Katherine:

Well, speaking of information, there is a lot out there, some of which may not be very reliable. And that could lead many patients to having misconceptions about clinical trials. Let’s walk through a few common concerns we’ve heard from our community about trials. 

One frequent question is – will I receive a placebo instead of a real treatment? And, first, I’d like you to define placebo. And should this be a concern for patients? 

Dr. Subudhi:

Right. So, placebo is a drug that looks similar to the experimental drug. For example, if the experimental drug is a blue pill, then the placebo will be a blue pill. But it will be a pill that should have no known biological activity.  

If the experimental drug is given intravenously and you get it in a liquid bag, then the placebo will also come in a liquid bag. So, it will look the same. And that’s why both the medical team as well as the patients or their families will not know which drug the patients have received, meaning the experimental drug or the placebo. But the placebos are meant to not have any biological activity. 

Katherine:

So, it shouldn’t be a concern to patients then.   

Dr. Subudhi:

Well, the concern that most of my patients share with me when they hear about placebo-controlled trials is, “Well, if I’m not going to get the experimental drug, why should I do this? I mean what benefit does it have for me?” And so, I tell them that one of the benefits is that we are watching you very carefully. 

Because we don’t know sometimes which drug you’re getting. But in some control trials, like a randomized control trial, we will know because I’m not blinded.  

If you’re in the arm that’s only getting chemotherapy, well, you know you’re not getting an oral pill. So, it’s very clear to the patient what they’re getting. But if they’re getting an oral pill that’s a placebo, we’re watching them very carefully.  

So, we’re watching the patients very carefully in these placebo-controlled trials. And they’re coming in often so that we’re not going to miss any devastating things happening from the cancer. In fact, we’ll pick it up earlier than if they were just getting a standard of care outside of a trial. And for that reason I tell that my patients, “Don’t be worried.” And I always make sure that I have a backup plan. 

So, the backup plan is either they’re going to cross over, meaning the trial allows for them to cross over to get the experimental drug. Or I have another trial that I know that they will qualify for. Or the third alternative is that I actually have a standard of care drug that I’m ready to give them the second I have it so that they don’t have to have those concerns. 

Katherine:

That’s really great information to have. Patients also often have questions about safety. So, what are the risks of clinical trial participation? 

Dr. Subudhi:

So, safety is a major issue, especially more into the Phase I. The Phase I trial, if you remember, are the trials where we’re dose escalating, meaning we start off with a small cohort of patients, maybe three to five patients. And we give one dose of the drug. We see if it’s safe. If it’s safe, then we go to the next dosing level. And we just keep going until we find a dose that may be too toxic or too unsafe for our patient. 

So, in the Phase I, we have less information, especially in the first-in-human drugs. But in those cases, we are watching you carefully to make sure that nothing bad happens to you. 

But the problem with those trials is it requires a lot of time at the institution or with your doctor. For example, I’m doing a bispecific trial where we have to keep the patients inside the hospital for eight days, purely for safety reasons. They’re not getting the drug for all eight days. But we’re just keeping them under observation so in case anything bad happens we’re ready to react because we know that if something bad happens at their home in that first eight days, it could actually risk their lives. 

So, in those cases, some trials, if we’re concerned about safety, you’ll be spending more time in the doctor’s office or in a hospital being evaluated. So, that’s the one negative. But sometimes, the trials that can be more exhausting as far as the amount of time it takes you away from your home and family are the ones that have the most reward. 

Katherine:

Well, what protocols are in place to protect patients? 

Dr. Subudhi:

So, when they sign up for a protocol, we are instructed to give them our best information. So, let’s say it’s a first-in-human drug. Well, usually, first-in-human drugs are tested in other mammals, such as monkeys, and we look for toxicities there. And we have signs of what’s going to happen. Sometimes, a first-in-human drug is part of a class of drugs, like I talked to you about T-cell bispecifics. 

Well, there’s several T-cell bispecifics out there. And we’ve learned that this class of drugs has a unique set of side effects that they all tend to have. Some have it more, and some have it less. 

But when we’re discussing this with you or the patient, we are actually going to go through each and all of these side effects. Now, me personally, my patients that go on my trials, they all get my cellphone number so they have 24/7 access to me because I know they’re taking a risk. And it’s a lot of courage to go on these trials. And it’s scary. And I want to make sure they don’t feel like they’re ever alone. 

Katherine:

Another common concern we hear is that a clinical trial is only considered when there are no other treatment options available for a patient. What are your thoughts on this? 

Dr. Subudhi:

There’s a lot of my colleagues in the field that feel that way. And I know a lot of patients’ misconceptions are also that way. And that’s partly because of Hollywood and movies and TV shows that we watch. But I think that many people, especially in the medical field, think of clinical trials as the last resort. 

And I actually disagree with that. I think that I like to actually start my patients with one or two standard of care treatments. But after that, really start putting clinical trials in between. And we have to remember that there’s not always a clinical trial available that the patient actually meets the criteria for.  

So, it’s always disheartening in clinic when I meet someone for the very first time who was referred to me because they exhausted everything. And we just don’t have any clinical trials available, or they’re so weak from the cancer and all the prior treatments that they don’t qualify for a clinical trial. And then I really don’t have anything else to give them.  

So, my personal approach is to try to put clinical trials in between and always have something in my back pocket so that if they get a bit exhausted or they want to spend more time with friends and family, they can get the standard of care treatment. 

Katherine:

If a patient is interested in participating in a trial, what’s the best way to find out which trials might be available for them and right for them? 

Dr. Subudhi:

So, that’s a great question. I think number one is always ask your oncologist, and they’re a great resource. But also, there’s websites. So, for different types of cancer – so, example, I do prostate cancer. So, the Prostate Cancer Foundation or PCF.org is a wonderful resource that will give you a list of cutting-edge trials. 

In addition, the government has clinicaltrials.gov. And that’s where you can actually type in your cancer type and different criteria, and you’ll get a list of trials. 

Katherine:

That’s good to know. What questions should patients ask their healthcare team when considering joining a trial? 

Dr. Subudhi:

I would ask them, “Would you do it yourself if you were in my situation?”  

Katherine:

Very good. 

Dr. Subudhi:

I think that’s a very important thing to ask.  

Katherine:

Are there barriers that interfere with patients’ access to clinical trials? I think you touched on this but maybe if you have anything to add.

Dr. Subudhi:

Yeah. So, travel can be a major barrier. And that’s something that the pharmaceutical industry understands. And, therefore, some of the trials, especially the multicenter trials, actually allow for travel cost. That sometimes includes flights, driving, hotels, food.  

So, that’s something that’s important to ask because sometimes when we’re thinking about clinical trials, we’re so anxious in the doctor’s office. And then it’s not until we go back home when we’re trying to figure out how do we get the resources to come so frequently. You’ll find out that’s sometimes travel costs. 

The other thing is underrepresented minorities are something that we’ve been doing a relatively poor job recruiting to our clinical trials. Part of that is just from history that we didn’t have the safety rules in place that we do now. And underrepresented minorities were affected negatively in some of the earlier trials.  

And the other thing is just the resources of getting to and from their homes to our cancer site as often as they need to because they may be the sole breadwinner in their homes and things like that. So, there are resources to try to help do this. But I still think we have to do a better job. 

Katherine:

Can trials be coordinated between a local doc and the institution? 

Dr. Subudhi:

So, most trials cannot. Most. But there are some that can. So, if it’s a standard of care treatment, sometimes we can have the safety visits done with the local doctors. But every time they’re going to get the treatment they have to come see us at the institution that is actually running the trial.   

But most of the time, what I tell all my patients is, “I want them to have a local doctor.” Because if there’s something that happens in the middle of the night, I want to be able to say, “You’re going to go to this emergency room where this doctor works.” And then when they go there, as soon as they get admitted into the emergency room center, I talk to the ER doctor, and I say, “This is what I want to be done. These are how these drugs work.” 

Because they’re not going to know what these experimental drugs are. They’re not available in the community. So, I just think it’s important to have communication, especially for our patients that are out of state. MD Anderson is in Houston, Texas. And Texas is so big that a lot of my patients live six to eight hours away, and they’re still in Texas. 

Katherine:

Oh, wow. So, what are your thoughts on what could be done to overcome the barriers that some patients are experiencing? And are there resources available?  

Dr. Subudhi:

So, the pharmaceutical companies are putting in more financial resources as well as a diversity resource. And when I say diversity resources, those outreach programs just to make sure that the communities that are underserved are hearing about the clinical trials because if you don’t hear about it you’re never going to join it. So, one thing is just knowledge. 

And then, number two, we’re trying to create financial resources. For example, there’s Angel Flight as one example where they will pay for the flight for you. And they’ll put you on maybe a chartered plane or something or a smaller plane to defray the cost of traveling by air. So, there are things out there, but we still need a lot more. 

Katherine:

But one thing patients could do is talk to their healthcare team about what resources are available for them.  

Dr. Subudhi:

Absolutely. Absolutely. 

Katherine:

Before we end the program, Dr. Subudhi, I’d like to get your final thoughts. What message do you want to leave the audience with related to clinical trial participation? 

Dr. Subudhi:

First of all, thank you for even thinking about it. That’s the one big step. And for those of you who actually take the next step and actually join a clinical trial, again, thank you for being so brave. 

I think it’s a gift that you’re giving to other fellow patients with cancer. And it’s also a gift that you’re giving to the scientific and medical community, because we are learning by your participation in the trial. And I want you to know whether the trial worked for you or does not work for you, regardless, we’re going to learn something that’s going to help change outcomes in your cancer. 

Katherine:

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

Dr. Subudhi:

Well, thank you. I really appreciate it.  

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 programs in the future. To learn more about prostate cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thank you for being with us. 

Does Maintenance Therapy Have a Role in AML Care?

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Does Maintenance Therapy Have a Role in AML Care? from Patient Empowerment Network on Vimeo.

Acute myeloid leukemia (AML) expert Dr. Farhad Ravandi-Kashani discusses the role of new and developing maintenance therapies that may improve remission and how this treatment phase may fit into the future of AML care.

Dr. Farhad Ravandi-Kashani is professor of medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, TX. Learn more about Dr. Ravandi-Kashani.

See More From INSIST! AML


Related Resources:

How Does the Presence of Molecular Markers Affect AML Care

Diagnosing and Treating AML_ What Testing Is Essential

Advances in AML Research _ Where Do Clinical Trials Fit In

Transcript:

Laura Beth:

Dr. Ravandi, does maintenance therapy have a role in AML?  

Dr. Ravandi:

Maintenance therapy is something that has been used in other leukemias for a long time, and other types of cancer, particularly in ontological cancers. In AML, it hasn’t been normal practice, traditionally, mainly because in AML, we haven’t had many good relatively nontoxic, easily taken drugs.  

So, about 30 years ago, some groups, for example, a German group actually tried to do maintenance with cycles of chemotherapy, and you can imagine if a patient is in remission, and somebody says to you, “I’m going to give you cycles of chemotherapy for the next three years,” most patients wouldn’t take it because they say, “Well, you know, maybe I have three years to live. I want to go to Bahamas and be on the beach rather than getting cycles of chemotherapy.” But over the last several years, in a number of effective, highly effective oral agents that have been developed, and one specific agent that has been developed for maintenance. Now, this specific agent is not curative, as it’s not that if you take it, you will live forever.  

But it does improve survival, and it’s relatively well-tolerated. And there are other clinical trials of maintenance. Agents are being developed, and I think it’s a very important area in AML. And I think in the next several years, it will actually become common practice to do maintenance regimens.  

Laura Beth:

That’s good news. So, once an AML patient is in remission how are they monitored? 

Dr. Ravandi:

So, I mean, I usually tell my patients that once you’re in remission, you’re in remission until something goes wrong with your blood counts. So, in my opinion, it’s not important to do – definitely not important to do weekly blood counts, for example.  

Depending on patient’s anxiety levels and comfort, we do check their labs maybe once a month, once every two or three months, depending on how far they are from their remission. And in my opinion, routine bone marrows are not necessary during remission, unless the patient is a part of a clinical trial that they have accepted to participated in, because we do get a lot of information by doing those bone marrows. So, some studies have follow-up bone marrows, but that’s really as a part of a clinical trial and to help further the knowledge in therapy.  

Advances in AML Research | Where Do Clinical Trials Fit In?

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Advances in AML Research | Where Do Clinical Trials Fit In? from Patient Empowerment Network on Vimeo.

How do clinical trials advance acute myeloid leukemia (AML) research? Dr. Farhad Ravandi-Kashani discusses newer AML treatments that have changed the landscape of care and how patient trial participation moves research forward.

Dr. Farhad Ravandi-Kashani is professor of medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, TX. Learn more about Dr. Ravandi-Kashani.

See More From INSIST! AML


Related Resources:

How Does the Presence of Molecular Markers Affect AML Care

Diagnosing and Treating AML_ What Testing Is Essential

Does Maintenance Therapy Have a Role in AML Care

Transcript:

Laura Beth:

When it comes to AML research and emerging treatment options, what are you excited about right now?  

Dr. Ravandi:

Well, I think one of the biggest, I would call, revolutionary changes in AML was the introduction of venetoclax (Venclexta), because AML is a disease of the older population.  

The median age is about 68, which means half of the patients are older than 68, and among the other half, majority are older than 55. And when you go beyond 60, 65, traditional chemotherapy is not well-tolerated. But the introduction of venetoclax plus azacitidine (Onureg) or decitabine (Dacogen), depending on the center, has really completely changed the management of older AML patients from a situation that it was dismal treatment to a situation that’s still not great, but it’s a lot better, as in we don’t cure the majority, but many people have a tolerable therapy and live with their disease for several months if not several years.  

And personally, I have treated a 97-year-old patient, and she did well for three years, so. Because of this drug, age is no longer as frightening as it used to be for advanced age. 

Laura Beth:

So, where do clinical trials fit in when it comes to choosing treatment?   

Dr. Ravandi:

So, the best drugs that we have available now, the venetoclax that I mentioned and all the other drugs that I mentioned, targeted drugs, came from clinical trials.  

If we don’t do clinical trials, we would be still doing the same treatments that we were doing in the 1970s and ‘80s.  

In fact, up until about seven or eight years ago, many places were still doing the same treatments that was developed in 1970s, which in the era of computers, and Apple, and everything else, it’s mindboggling that we should be doing something that we were doing in the ‘70s. So, clinical trials are important to move the field forward. They are at major academic centers, all the clinical trials are extremely well-vetted and scientifically vetted, as well as with institutional review boards, ethically vetted. So, patients can be sure that they’re not going to get anything less and potentially more than what they would normally get.  

How Does the Presence of Molecular Markers Affect AML Care?

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How Does the Presence of Molecular Markers Affect AML Care? from Patient Empowerment Network on Vimeo.

Dr. Farhad Ravandi-Kashani reviews how the presence of gene mutations can influence acute myeloid leukemia (AML) treatment choices and discusses new molecular markers being researched for future AML care.

Dr. Farhad Ravandi-Kashani is professor of medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, TX. Learn more about Dr. Ravandi-Kashani.

See More From INSIST! AML


Related Resources:

Diagnosing and Treating AML_ What Testing Is Essential

Advances in AML Research _ Where Do Clinical Trials Fit In

Does Maintenance Therapy Have a Role in AML Care


Transcript:

Laura Beth:

How do test results impact AML care and treatment decisions?  

Dr. Ravandi:

So, in the first place, the presence or absence of certain mutations can be predictable outcome. Some subsets of leukemias are, for the lack of a better term, more favorable.  

I personally don’t think there is anything favorable about any leukemia, but some are easier to treat, and some are easier to cure than others. There is one specific subtype called acute promyelocytic leukemia that we actually completely treat differently. We don’t use even chemotherapy in that subset of leukemia.  

It has almost 100 percent success rate. And the treatment of other subsets can also be tailored, depending on these molecular and chromosomal changes. So, the initial therapy can be actually changed. There are now, for example, targeted agents that can be added to the chemotherapy, during initial chemotherapy.  

And also, once the patient is in remission, depending on favorable or unfavorable their leukemia is, they may be offered allogeneic stem cell transplant. So, yes, this information is highly important. In fact, I would say crucial for our decision-making in leukemia therapy these days.  

Laura Beth:

So, what is new in AML research related to molecular markers?  

Dr. Ravandi:

Well, it depends on your definition of new, but FLT3 mutations are very important because they’re now several FLT3 inhibitors, and as I mentioned, the initial therapies are different, to some extent. The IDH mutations are very important, again, because they are specific targeted agents.  

TP53 mutations are important because, unfortunately, they are particularly unfavorable.  

This is completely hot off the press, but there are subsets of AML called MLL rearranged leukemias that can respond to these drugs called Menin inhibitors.  

There are other mutations that have been discovered, many other ones, that there are no specific treatments for at the moment, but there’s a lot of research on.  

Diagnosing and Treating AML: What Testing Is Essential?

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Diagnosing and Treating AML: What Testing Is Essential? from Patient Empowerment Network on Vimeo.

How do test results affect the diagnosis and care of patients with acute myeloid leukemia (AML)? Dr. Farhad Ravandi-Kashani reviews essential testing for AML patients, including molecular testing and what these test results might reveal about the disease.

Dr. Farhad Ravandi-Kashani is professor of medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, TX. Learn more about Dr. Ravandi-Kashani.

See More From INSIST! AML


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Advances in AML Research _ Where Do Clinical Trials Fit In

Does Maintenance Therapy Have a Role in AML Care


Transcript:

Laura Beth:

Dr. Ravandi, can you define molecular testing for AML patients?  

Dr. Ravandi:

We have progressed on our understanding of cancer, in general. And we have progressed in our technology, so we know that various cancers are likely caused by a number of molecular events, and this is best characterized in leukemias because we have been doing this in leukemia for many years now, simply because leukemias are much more accessible than other cancers. Leukemic cells are in blood and easily obtained and even in bone marrow, are much easier obtained than other solid tumor cancers.  

And so, we’ve been able to identify a number of gene and chromosome changes that we have discovered to be prognostic, but also, have become the targets for developing effective drugs.  

Laura Beth:

Beyond molecular testing, what other testing should take place following an AML diagnosis?  

Dr. Ravandi:

I mean, the classical patient presents because there is something in their blood counts, so they usually have had a blood count testing done. And, of course, you need to do a number of other tests, for example, the chemistry profile, because that can show us some of the problems that can be caused by leukemia.  

And the most important thing is bone marrow aspiration and biopsy, which is still, unfortunately, absolutely necessary, first to make the diagnosis, and second, to obtain the specimens for those biomarker testing that you mentioned.  

Laura Beth:

If a patient relapses, does all of this testing need to be repeated?  

Dr. Ravandi:

Unfortunately, yes. And so, when you said all of these testing, actually, again, compared to some other cancers, this is limited testing. Taking blood for the blood tests, and even doing a bone marrow is generally much easier than taking tissue in a colonoscopy for a colon cancer, or doing a biopsy, a lung biopsy in lung cancer, etc.  

But yes, they all need to be tested, and actually, we do like to repeat the genetic testing because leukemias are dynamic, and after initial therapy, they may change in ways. They may develop new targets or new molecular changes that may be potentially amenable to new targeted therapies.  

Laura Beth:

And is it common for a mutation to appear at a relapse?  

Dr. Ravandi:

It is, yes. I mean, I would say it’s – I wouldn’t say it’s common, but it is frequent.  

Advice for Speaking Up About Your DLBCL Care

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Advice for Speaking Up About Your DLBCL Care from Patient Empowerment Network on Vimeo.

Why should you speak up about your DLBCL care? Dr. Jason Westin explains why being an active member of your healthcare team is vital and provides helpful resources.

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.

See More From The Pro-Active DLBCL Patient Toolkit

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Tips for Making Treatment Decisions WITH Your DLBCL Team

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What Helps Determine a Patient’s DLBCL Treatment Path?


Transcript:

Katherine:                  

Right. That leads me to my next question. What advice do you have for patients who don’t feel comfortable speaking up but they have questions about their treatment plan?

Dr. Westin:                 

Yeah. I think written questions sometimes are easier than trying to remember all of your questions. It always is a bit problematic when I go into a visit and a patient has six pages of paper written down for questions. We unfortunately don’t have unlimited time to get through all of those. But trying to condense into – prioritizing. Which of the questions are the ones that I feel like I must get into and which are ones that I can submit to have answered after the fact.

Perhaps the nurse could send me a note through the electronic medical record to answer questions 10-15 on my list. So, I think you can overwhelm a visit if you show up with a list of questions that are even 30-second answers might take an hour to answer all of them. That’s sometimes counterproductive, in my opinion, to have that level of detail on a single visit. But it’s fair to say, “Can I contact the healthcare team to get these answered electronically through the EMR,” or, “Can we table this and go into the questions that we didn’t get to at our next visit?” I think both of those are appropriate.

I think people that are not comfortable to push back on the physician, or the PA, or the nurse, doing things in writing sometimes feels a little bit less confrontational for people. So, I think that’s important to have as a backup option.

Katherine:                  

And I imagine caregivers can be helpful in this regard as well.

Dr. Westin:                 

Correct. Yeah. I think caregivers are a key part of that. And sometimes we go into a room and the patient says, “Nope. Don’t have any questions.”

And then, the caregiver has got a whole list of them. That’s very appropriate. Caregivers have that responsibility and that role to play sometimes, to be the key questioner.

Katherine:                  

Yeah. Are there resources to help patients and their loved ones to weigh the risks and benefits of different treatment options?

Dr. Westin:                 

There are. There’s lots of resources online and I would make sure that you go to a trusted site. Sometimes things sound too good to be true because they’re not true. But things like the lymphoma research foundation or the LLS, the Lymphoma & Leukemia Society, are great sources for information. And sometimes they may link you to other sites. You could also ask your healthcare provider does their institution have anything specific about this disease. Sometimes your healthcare provider might tell you, “Here’s the right article if you want to go read the source, the clinical trial, that was published to show why this treatment’s good.” They may show you that paper.

But online, careful how deep into the weeds you go because sometimes you can find things that aren’t correct. Trust good, trusted sources.

Katherine:                  

Do you think patients should consider a second opinion consult with a specialist?

Dr. Westin:                 

It sometimes is appropriate. Other times, there’s not a lot of time. If treatment’s needed right away, you don’t want to get sicker because you’re waiting for seeing somebody two states over and it takes two weeks to get there. Sometimes you want to start treatment and get the second opinion after you’ve got the fire put out. But the second opinion usually gives more peace of mind than actually changing treatments. But if you’ve got that thought of, “I’m not so sure this is what I’d like to do,” or, “I’d like to get more information,” a second opinion may be very appropriate.

Tips for Making Treatment Decisions WITH Your DLBCL Team

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Tips for Making Treatment Decisions WITH Your DLBCL Team from Patient Empowerment Network on Vimeo.

DLBCL expert, Dr. Jason Westin, explains shared decision-making and provides tips for engaging in your treatment decisions.

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.

See More From The Pro-Active DLBCL Patient Toolkit

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Advice for Speaking Up About Your DLBCL Care

Who Are the Members of Your DLBCL Care Team?

Who Are the Members of Your DLBCL Care Team?

What Helps Determine a Patient’s DLBCL Treatment Path?

What Helps Determine a Patient’s DLBCL Treatment Path?


Transcript:

Katherine:                  

Lately, we’ve been hearing this term shared decision-making, which basically means the patients and clinicians collaborate to make healthcare decisions. And it can help patients take a more active role in their care. So, I’d like to get your thoughts on how best to make this process work. Are there questions that patients should consider asking about their proposed treatment plan?

Dr. Westin:                 

Definitely. And I think shared decision-making is something that we view to be critical. We want everybody on board to feel like they’ve got some sense of ownership of these decisions and that they’re involved in a way that’s meaningful. At the end of the day, the patients make the decisions about which treatments are right for them but they’re trusting their healthcare team to give them good advice. This is not something that patients have expertise in. This is often out of nowhere that somebody is newly diagnosed and this is not on their radar, not something that they ever thought that they’d be sitting in the chair talking about which type of therapy for this cancer.

And so, patients are often relying on the healthcare team to give them good advice. But it’s a fair question and it’s, I think, one that’s appropriate to ask. “Are there other treatment options that we should be talking about?” Basically, exploring, “Is this option you’re presenting the option or is this what you consider to be the best option.” Oftentimes physicians, and PAs, and nurse practitioners might filter information such that, “Yeah, there are other options but here’s why they’re bad. Here’s why they’re not right for you.”

But feeling that you have some clarity about why a treatment choice was made, I think, is often quite important. For first line DLBCL, there are less options to consider. But in the relapse space, there are lots of options. And those should be discussed. And sometimes the healthcare provider, a physician, might have their favorite that they have had good experience with treatment A and therefore they recommend treatment A to the next patient. But that may not always be the right treatment for a given patient.

There may be reasons to consider other treatments. And so, asking that question, “What else is out there? What other treatments are there? Anything else that we should be considering,” I think is a fair question to ask and an important one. And if the answer is, “No, there aren’t other treatment options. This is the one that we should choose,” at least you’re aware of that by asking that question. So, I think that’s an important one to clarify.

What Helps Determine a Patient’s DLBCL Treatment Path?

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

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

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

See More From The Pro-Active DLBCL Patient Toolkit

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Transcript:

Katherine:                  

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

Dr. Westin:                 

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

Katherine:                  

Right.

Dr. Westin:                 

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

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

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

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

Katherine:                  

Can you touch upon treatment side effects?

Dr. Westin:                 

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

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

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

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

Katherine:                  

Yeah.

Dr. Westin:                 

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

Emerging DLBCL Treatment Approaches

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Emerging DLBCL Treatment Approaches from Patient Empowerment Network on Vimeo.

What is next for DLBCL treatment? Dr. Jason Westin describes emerging DLBCL treatment approaches.

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

See More From The Pro-Active DLBCL Patient Toolkit

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Advice for Speaking Up About Your DLBCL Care

What Helps Determine a Patient’s DLBCL Treatment Path?

What Helps Determine a Patient’s DLBCL Treatment Path?

Tips for Making Treatment Decisions WITH Your DLBCL Team


Transcript:

Katherine:                  

Yeah. You touched upon this earlier, Dr. Westin, but aren’t there emerging DLBCL approaches the patient should know about?

Dr. Westin:                 

Yes. Thankfully, there are many, many. We could spend several hours talking about lots of new therapies coming along. So, it’s a great answer to have. It’s an embarrassment of riches that we have for lots and lots of new therapies that appear quite promising in the early development stage.

In terms of those that have actually crossed over the finished line to be approved by the FDA, we have a handful of new therapies in the past few years that have been approved. Previously, we didn’t really have very many, but now there are multiple therapies that are approved by the FDA outside of a clinical trial, that are targeted treatments.

And those include antibody drug conjugates, basically an antibody like you make against an infection. However, this antibody has a chemotherapy warhead attached to the back of it. So, effectively, it’s a heatseeking missile that finds whatever target we want it to find – in this case, cancer cells – and delivers a high dose chemotherapy right to the bad guys, not to the good guys. There are also other immune therapies that we’ve seen than can be very powerful antibodies, plus immunomodulatory drugs. And we can talk about specific names of these if we’d like.

And then, lastly, there are other oral agents that are coming along that look very promising in terms of their ability to target the cancer cells more directly than growing cells.

Lastly, there’s a very new class of therapies not yet approved, but very promising. I mentioned this before. It’s something called a bispecific antibody. Bispecific – the word bicycle meaning two wheels. Bispecific is two specific antibodies. Basically, it’s an antibody that’s grabbing onto a cancer cell and grabbing onto an immune cell. “I’d like to introduce you guys. Why don’t you guys come in proximity and see if we can have a party.”

And it’s an idea here of trying to get the cancer cell to be attacked by the immune cell simply through this close proximity that occurs. Not yet approved. Looks very promising and I think probably will be approved for multiple different lymphoma types, including large B-cell, in the coming years.

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.

See More From The Pro-Active DLBCL Patient Toolkit

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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.

An Expert Overview of DLBCL Treatment Approaches

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

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

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

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What Helps Determine a Patient’s DLBCL Treatment Path?

How Can You Access DLBCL Clinical Trials?


Transcript:

Katherine:                  

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

Dr. Westin:                 

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

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

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

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

Katherine:                  

And what about CAR T-cell therapy?

Dr. Westin:                 

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

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

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

Katherine:                  

And what about stem cell transplant?

Dr. Westin:                 

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

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

Understanding Your DLBCL Treatment Goals

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Understanding Your DLBCL Treatment Goals from Patient Empowerment Network on Vimeo.

 What are the goals of DLBCL treatment? Expert Dr. Jason Westin explains how treatment goals and timing are established.

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.

See More From The Pro-Active DLBCL Patient Toolkit

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Emerging DLBCL Treatment Approaches

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An Expert Overview of DLBCL Treatment Approaches

How Can You Access DLBCL Clinical Trials?


Transcript:

Katherine:                  

Before we move on to discuss the types of treatment, what are the goals of DLBCL treatment and how do they vary by patient.

Dr. Westin:                 

It’s a very important question to define at the outset what are we trying to accomplish when we’re talking about different treatments that we could recommend. DLBCL is a curable disease but, unfortunately, we don’t cure as many patients as we’d like. The majority of patients are cured but we always want to try and do better. But at the outset, we define our goals. And if somebody’s newly diagnosed, the goals of treatments is to try and go for a cure. That’s the end of that sentence when I am talking to my patient, that we are going for a cure, period. And then, we describe how we get there.

If somebody has relapsed or refractory disease, if the first treatments don’t work, usually we’re still trying to go for a cure, but there are some contexts where a curative treatment may be too toxic, the treatment itself may be a bad idea, just because of the potential of toxicities to be too much for a patient to tolerate.

So, there are situations, if the patients had a cancer that’s not gone away with the standard approach, sometimes we’re still going for a cure. Sometimes that may be difficult to achieve and we’d be going for a palliative treatment to try and prolong the patient’s quality of life and to try and give the patient more good days without harming them with treatments. But by and large, when we’re talking about the category or large B-cell lymphoma, the intention of treatment is to go for a cure.

Katherine:                  

How can patients make sure they understand their goals of treatment?

Dr. Westin:                 

It’s important to ask physicians, and PAs, and nurses at the outset about the goals of treatment. Sometimes we move quickly from diagnosis to treatment and don’t necessarily take a moment to talk about, “What are we trying to accomplish with this treatment?” We just see a fire and we’re trying to put it out. And the patient’s excited to get started after the scare of a diagnosis.

But I do think clarifying, “Can we talk a little bit about what the goal of this treatment is” – because sometimes there can be a mismatch between what a patient might expect a goal is and a physician, or a PA, or a nurse might expect a goal is. And if we’re not clarifying that and on the same page about that, sometimes there could be conflicts or confusion as we go into the treatments.

Katherine:                  

All right. I think we have a good understanding of treatment goals. So, when is it time to treat DLBCL?

Dr. Westin:                 

DLBCL is not a cancer that we wait to treat. This is a cancer that needs treatment very quickly after diagnosis. If a patient were not treated, the cancer would progress very rapidly. Some DLBCL’s progress faster than others but we would expect that if treatments were not administered, if we lived a century ago when treatments didn’t really exist, people would live, at the most, a few months with this cancer. This is a rapidly growing cancer that would result in death if we didn’t take care of it.

So, the time to initiate treatment is basically after a biopsy is obtained, the pathologist says, “This is large B-cell lymphoma,” a meeting with and oncologist occurs that says we got to start a treatment. Than then, ASAP after that to get going. What we know from DLBCL patients in the past is those that require treatment sooner – meaning you get a biopsy on a Monday and by Friday night you’re sick and you need treatment now or else – that tends to go along with a more aggressive version of DLBCL and perhaps can be associated with worse outcomes.

Patients who get a biopsy and four weeks later then they’re in the oncologist’s office talking about, “Maybe we should start a treatment,” but no symptoms, no problems, that usually goes along with a better prognosis. The so-called diagnosis to treatment interval can be actually powerfully prognostic.

Who Are the Members of Your DLBCL Care Team?

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Who Are the Members of Your DLBCL Care Team? from Patient Empowerment Network on Vimeo.

Lymphoma expert Dr. Jason Westin describes the key members of a multidisciplinary DLBCL care team.

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.

See More From The Pro-Active DLBCL Patient Toolkit

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Understanding Your DLBCL Treatment Goals

An Expert Overview of DLBCL Treatment Approaches

An Expert Overview of DLBCL Treatment Approaches

How Can You Access DLBCL Clinical Trials?


Transcript:

Katherine:

Today, we’re going to be learning about DLBCL treatment goals and how patients can be active members of their team. So, let’s start by understanding who is typically on a patient’s DLBCL healthcare team.

Dr. Westin:                 

It’s a good question. The members of the DLBCL healthcare team usually consist of a physician – and this person usually would start the process of saying, “This is something. I don’t know what’s going on with this mass or this pain you’re having. Let’s get some imaging. Let’s get a biopsy to figure out what’s going on.” There would often be a nurse as a member of the team. And the nurse usually provides a critical service in terms of help – facilitating patients to understanding what’s going on and to work with the healthcare team directly to provide excellent patient care.

And eventually, there would often be a pharmacist involved in terms of the chemotherapy or treatments that are administered to help review those and work with the physician and the nurse directly. Those would be the main members of the healthcare team. Occasionally, there might be a social worker or there might be other care providers that are involved. But usually, it’s the physician, the nurse. And then, sometimes the physician extender, such as a PA or a nurse practitioner.

Katherine:                  

Okay. What do you feel is the patient’s role as a team member.

Dr. Westin:                 

Patients are a critical part of our team and are often the decider of what goes on. The physicians, nurses, PAs, pharmacists – our jobs are to help educate the patient and to help the patient to decide what the best treatment is.

Ultimately, it’s the patient’s responsibility to understand what’s going on, to ask good questions, and then to make a decision about what treatments are best for them.

Katherine:                  

What role do caregivers take?

Dr. Westin:                 

Caregivers often play a very important role, and it’s variable from person to person how involved a caregiver is. But if patients have symptoms or side effects of treatment, caregivers are often critical to make sure patients get the appropriate medical care that they need. Some treatments may have more potential for side effects than others. Sometimes, caregivers are essential to actually stay with a patient, even during admission to the hospital to make sure the patients are monitored closely.

And we may talk about different treatments later in the interview. But at our center, sometimes we even mandate that there are caregivers involved in the sense of staying with the patient in the hospital for certain therapy types. But in general, being a supportive family member or caregiver, it’s a good thing to have even if we don’t have a lot of toxicity for emotional and physical support. But sometimes it’s really important to help manage toxicities.

How to Play an Active Role in Your DLBCL Treatment and Care Decisions

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How to Play an Active Role in Your DLBCL Treatment and Care Decisions from Patient Empowerment Network on Vimeo.

What steps can you take to engage in your diffuse large b-cell lymphoma (DLBCL) treatment and care decisions? Expert Dr. Jason Westin discusses current and emerging DLBCL therapies, reviews key treatment decision-making factors, and shares advice for partnering with your healthcare team.

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:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re going to explore the goals of DLBCL treatment and discuss how you can play an active role in making care decisions.

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.

Joining us today is Dr. Jason Westin. Dr. Westin, welcome. Would you please introduce yourself? Okay.

Dr. Westin:                 

Of course. Happy to be here. Thank you for inviting me. My name’s Jason Westin. I am the Director of Lymphoma Clinical Research and the Section Chief for Aggressive Lymphomas at MD Anderson Cancer Center of Houston, Texas.

Katherine:                  

Excellent. Thank you so much for taking time to join us today. Today, we’re going to be learning about DLBCL treatment goals and how patients can be active members of their team. So, let’s start by understanding who is typically on a patient’s DLBCL healthcare team.

Dr. Westin:                 

It’s a good question. The members of the DLBCL healthcare team usually consist of a physician – and this person usually would start the process of saying, “This is something. I don’t know what’s going on with this mass or this pain you’re having. Let’s get some imaging. Let’s get a biopsy to figure out what’s going on.” There would often be a nurse as a member of the team. And the nurse usually provides a critical service in terms of help – facilitating patients to understanding what’s going on and to work with the healthcare team directly to provide excellent patient care.

And eventually, there would often be a pharmacist involved in terms of the chemotherapy or treatments that are administered to help review those and work with the physician and the nurse directly. Those would be the main members of the healthcare team. Occasionally, there might be a social worker or there might be other care providers that are involved. But usually, it’s the physician, the nurse. And then, sometimes the physician extender, such as a PA or a nurse practitioner.

Katherine:                  

Okay. What do you feel is the patient’s role as a team member.

Dr. Westin:                 

Patients are a critical part of our team and are often the decider of what goes on. The physicians, nurses, PAs, pharmacists – our jobs are to help educate the patient and to help the patient to decide what the best treatment is.

Ultimately, it’s the patient’s responsibility to understand what’s going on, to ask good questions, and then to make a decision about what treatments are best for them.

Katherine:                  

What role do caregivers take?

Dr. Westin:                 

Caregivers often play a very important role, and it’s variable from person to person how involved a caregiver is. But if patients have symptoms or side effects of treatment, caregivers are often critical to make sure patients get the appropriate medical care that they need. Some treatments may have more potential for side effects than others. Sometimes, caregivers are essential to actually stay with a patient, even during admission to the hospital to make sure the patients are monitored closely.

And we may talk about different treatments later in the interview. But at our center, sometimes we even mandate that there are caregivers involved in the sense of staying with the patient in the hospital for certain therapy types. But in general, being a supportive family member or caregiver, it’s a good thing to have even if we don’t have a lot of toxicity for emotional and physical support. But sometimes it’s really important to help manage toxicities.

Katherine:                  

Right. Before we move on to discuss the types of treatment, what are the goals of DLBCL treatment and how do they vary by patient.

Dr. Westin:                 

It’s a very important question to define at the outset what are we trying to accomplish when we’re talking about different treatments that we could recommend. DLBCL is a curable disease but, unfortunately, we don’t cure as many patients as we’d like. The majority of patients are cured but we always want to try and do better. But at the outset, we define our goals. And if somebody’s newly diagnosed, the goals of treatments is to try and go for a cure. That’s the end of that sentence when I am talking to my patient, that we are going for a cure, period. And then, we describe how we get there.

If somebody has relapsed or refractory disease, if the first treatments don’t work, usually we’re still trying to go for a cure, but there are some contexts where a curative treatment may be too toxic, the treatment itself may be a bad idea, just because of the potential of toxicities to be too much for a patient to tolerate.

So, there are situations, if the patients had a cancer that’s not gone away with the standard approach, sometimes we’re still going for a cure. Sometimes that may be difficult to achieve and we’d be going for a palliative treatment to try and prolong the patient’s quality of life and to try and give the patient more good days without harming them with treatments. But by and large, when we’re talking about the category or large B-cell lymphoma, the intention of treatment is to go for a cure.

Katherine:                  

How can patients make sure they understand their goals of treatment?

Dr. Westin:                 

It’s important to ask physicians, and PAs, and nurses at the outset about the goals of treatment. Sometimes we move quickly from diagnosis to treatment and don’t necessarily take a moment to talk about, “What are we trying to accomplish with this treatment?” We just see a fire and we’re trying to put it out. And the patient’s excited to get started after the scare of a diagnosis.

But I do think clarifying, “Can we talk a little bit about what the goal of this treatment is” – because sometimes there can be a mismatch between what a patient might expect a goal is and a physician, or a PA, or a nurse might expect a goal is. And if we’re not clarifying that and on the same page about that, sometimes there could be conflicts or confusion as we go into the treatments.

Katherine:                  

All right. I think we have a good understanding of treatment goals. So, when is it time to treat DLBCL?

Dr. Westin:                 

DLBCL is not a cancer that we wait to treat. This is a cancer that needs treatment very quickly after diagnosis. If a patient were not treated, the cancer would progress very rapidly. Some DLBCL’s progress faster than others but we would expect that if treatments were not administered, if we lived a century ago when treatments didn’t really exist, people would live, at the most, a few months with this cancer. This is a rapidly growing cancer that would result in death if we didn’t take care of it.

So, the time to initiate treatment is basically after a biopsy is obtained, the pathologist says, “This is large B-cell lymphoma,” a meeting with and oncologist occurs that says we got to start a treatment. Than then, ASAP after that to get going. What we know from DLBCL patients in the past is those that require treatment sooner – meaning you get a biopsy on a Monday and by Friday night you’re sick and you need treatment now or else – that tends to go along with a more aggressive version of DLBCL and perhaps can be associated with worse outcomes.

Patients who get a biopsy and four weeks later then they’re in the oncologist’s office talking about, “Maybe we should start a treatment,” but no symptoms, no problems, that usually goes along with a better prognosis. The so-called diagnosis to treatment interval can be actually powerfully prognostic.

Katherine:                  

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

Dr. Westin:                 

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

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

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

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

Katherine:                  

And what about CAR T-cell therapy?

Dr. Westin:                 

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

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

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

Katherine:                  

And what about stem cell transplant?

Dr. Westin:                 

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

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

Katherine:                  

Okay. Good to know. 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.

Katherine:                  

Yeah. You touched upon this earlier, Dr. Westin, but aren’t there emerging DLBCL approaches the patient should know about?

Dr. Westin:                 

Yes. Thankfully, there are many, many. We could spend several hours talking about lots of new therapies coming along. So, it’s a great answer to have. It’s an embarrassment of riches that we have for lots and lots of new therapies that appear quite promising in the early development stage.

In terms of those that have actually crossed over the finished line to be approved by the FDA, we have a handful of new therapies in the past few years that have been approved. Previously, we didn’t really have very many, but now there are multiple therapies that are approved by the FDA outside of a clinical trial, that are targeted treatments.

And those include antibody drug conjugates, basically an antibody like you make against an infection. However, this antibody has a chemotherapy warhead attached to the back of it. So, effectively, it’s a heatseeking missile that finds whatever target we want it to find – in this case, cancer cells – and delivers a high dose chemotherapy right to the bad guys, not to the good guys. There are also other immune therapies that we’ve seen than can be very powerful antibodies, plus immunomodulatory drugs. And we can talk about specific names of these if we’d like.

And then, lastly, there are other oral agents that are coming along that look very promising in terms of their ability to target the cancer cells more directly than growing cells.

Lastly, there’s a very new class of therapies not yet approved, but very promising. I mentioned this before. It’s something called a bispecific antibody. Bispecific – the word bicycle meaning two wheels. Bispecific is two specific antibodies. Basically, it’s an antibody that’s grabbing onto a cancer cell and grabbing onto an immune cell. “I’d like to introduce you guys. Why don’t you guys come in proximity and see if we can have a party.”

And it’s an idea here of trying to get the cancer cell to be attacked by the immune cell simply through this close proximity that occurs. Not yet approved. Looks very promising and I think probably will be approved for multiple different lymphoma types, including large B-cell, in the coming years.

Katherine:                  

Okay. That’s really good information. Related to clinical trials and research, we received a patient question before the program. Anthony wants to know, “If I participate in a clinical trial, will I receive a placebo?”

Dr. Westin:                 

Great question, Anthony. I get this question all the time. The short answer is no in the way that you’re meaning this question.

Is there a possibility that you won’t get an active treatment for your cancer? No. That’s unethical. That’s not something that would ever been done in a clinical trial when there’s indication that treatment is needed. The only time a placebo might be used is to try and check to see is something effective more than what we’ve done in the past. An example being if we wanted to check a new drug in combination with R-CHOP, comparing it to R-CHOP alone, sometimes patients might get R-CHOP with the new drug or R-CHOP with a placebo.

Not a placebo by itself, but basically as a balance so that everybody’s taking an extra pill on top of their regular therapy. Because the placebo effect is powerful. Patients who take the new therapy, got the new pill, “I feel better because I’m doing this new targeted treatment.” When, in reality, placebos do that, too. So, it does help to have a balance in terms of symptoms, in terms of effectiveness in adverse events, to have placebo-controlled trials.

However, patients don’t get only a placebo. They get standard treatment plus a placebo. So, the only context I can think of you’d do that would be in that situation or if we think you’re already potentially cured but we’re giving an extra therapy just to be double sure versus observing the current standard. You may get a placebo there. But if you have active lymphoma that needs treatment, you will never get a placebo as your single therapy. That would be unethical and unacceptable. That does not happen.

Katherine:                  

Okay. That’s really good to know. Thank you.  Now that we have a better understanding of the types of treatment, let’s talk about what goes into deciding on an approach. Since no two patients are exactly the same, I imagine then that their treatment approaches are different. So, what do you consider when determining the best treatment option for an individual patient?

Dr. Westin:                 

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

Katherine:                  

Right.

Dr. Westin:                 

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

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

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

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

Katherine:                  

Can you touch upon treatment side effects?

Dr. Westin:                 

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

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

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

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

Katherine:                  

Yeah.

Dr. Westin:                 

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

Katherine:                  

Yeah. We had another audience question prior to the program. “Where can I find a specialist?”

Dr. Westin:                 

Very important question. It depends where you live. Specialists are not on every oncology shop in the country.

Katherine:                  

No.

Dr. Westin:                 

Lymphomas are not the most rare cancer. They’re somewhere in the seven, eight, nine range every year in terms of annual incidents of cancers. But that’s lymphomas in general. Large B-cell lymphoma is the most common lymphoma, but it represents about 30,000 new diagnoses each year. Thirty thousand Americans are diagnosed with this disease each year. Thirty thousand sounds like a large number if you’re thinking about a sporting event, but if you’re thinking about compared to the entire US population, that’s a relatively small number.

So, I think that going to a relatively large cancer center, if that’s something that’s feasible for you – if you live in a driving distance or have the economic means to be seen at a cancer center, you’re very likely to find a physician that has expertise in DLBCL. I practice at MD Anderson, where basically most of my patients have DLBCL. And I work in a department where all patients have lymphoma of various subtypes.

So, I have a somewhat unique position, where we’re able to drill down about subtypes of subtypes of subtypes and get into the weeds. Many physicians are able to keep up with the latest information for DLBCL, but may not be able to have that level of focus. I think it’s important to consider where you’re being treated as something that’s critical. And as mentioned before, asking about clinical trials. And if the place you’re at doesn’t have them or doesn’t want  to talk about them, maybe I should think about getting a second opinion someplace that might. 

Katherine:                  

Yeah. It sounds like there are several factors to weigh when making this decision about treatment. And lately, we’ve been hearing this term shared decision-making, which basically means the patients and clinicians collaborate to make healthcare decisions. And it can help patients take a more active role in their care. So, I’d like to get your thoughts on how best to make this process work. Are there questions that patients should consider asking about their proposed treatment plan?

Dr. Westin:                 

Definitely. And I think shared decision-making is something that we view to be critical. We want everybody on board to feel like they’ve got some sense of ownership of these decisions and that they’re involved in a way that’s meaningful. At the end of the day, the patients make the decisions about which treatments are right for them but they’re trusting their healthcare team to give them good advice. This is not something that patients have expertise in. This is often out of nowhere that somebody is newly diagnosed and this is not on their radar, not something that they ever thought that they’d be sitting in the chair talking about which type of therapy for this cancer.

And so, patients are often relying on the healthcare team to give them good advice. But it’s a fair question and it’s, I think, one that’s appropriate to ask. “Are there other treatment options that we should be talking about?” Basically, exploring, “Is this option you’re presenting the option or is this what you consider to be the best option.” Oftentimes physicians, and PAs, and nurse practitioners might filter information such that, “Yeah, there are other options but here’s why they’re bad. Here’s why they’re not right for you.”

But feeling that you have some clarity about why a treatment choice was made, I think, is often quite important. For first line DLBCL, there are less options to consider. But in the relapse space, there are lots of options. And those should be discussed. And sometimes the healthcare provider, a physician, might have their favorite that they have had good experience with treatment A and therefore they recommend treatment A to the next patient. But that may not always be the right treatment for a given patient.

There may be reasons to consider other treatments. And so, asking that question, “What else is out there? What other treatments are there? Anything else that we should be considering,” I think is a fair question to ask and an important one. And if the answer is, “No, there aren’t other treatment options. This is the one that we should choose,” at least you’re aware of that by asking that question. So, I think that’s an important one to clarify.

Katherine:                  

Right. That leads me to my next question. What advice do you have for patients who don’t feel comfortable speaking up but they have questions about their treatment plan?

Dr. Westin:                 

Yeah. I think written questions sometimes are easier than trying to remember all of your questions. It always is a bit problematic when I go into a visit and a patient has six pages of paper written down for questions. We unfortunately don’t have unlimited time to get through all of those. But trying to condense into – prioritizing. Which of the questions are the ones that I feel like I must get into and which are ones that I can submit to have answered after the fact.

Perhaps the nurse could send me a note through the electronic medical record to answer questions 10-15 on my list. So, I think you can overwhelm a visit if you show up with a list of questions that are even 30-second answers might take an hour to answer all of them. That’s sometimes counterproductive, in my opinion, to have that level of detail on a single visit. But it’s fair to say, “Can I contact the healthcare team to get these answered electronically through the EMR,” or, “Can we table this and go into the questions that we didn’t get to at our next visit?” I think both of those are appropriate.

I think people that are not comfortable to push back on the physician, or the PA, or the nurse, doing things in writing sometimes feels a little bit less confrontational for people. So, I think that’s important to have as a backup option.

Katherine:                  

And I imagine caregivers can be helpful in this regard as well.

Dr. Westin:                 

Correct. Yeah. I think caregivers are a key part of that. And sometimes we go into a room and the patient says, “Nope. Don’t have any questions.”

And then, the caregiver has got a whole list of them. That’s very appropriate. Caregivers have that responsibility and that role to play sometimes, to be the key questioner.

Katherine:                  

Yeah. Are there resources to help patients and their loved ones to weigh the risks and benefits of different treatment options?

Dr. Westin:                 

There are. There’s lots of resources online and I would make sure that you go to a trusted site. Sometimes things sound too good to be true because they’re not true. But things like the lymphoma research foundation or the LLS, the Lymphoma & Leukemia Society, are great sources for information. And sometimes they may link you to other sites. You could also ask your healthcare provider does their institution have anything specific about this disease. Sometimes your healthcare provider might tell you, “Here’s the right article if you want to go read the source, the clinical trial, that was published to show why this treatment’s good.” They may show you that paper.

But online, careful how deep into the weeds you go because sometimes you can find things that aren’t correct. Trust good, trusted sources.

Katherine:                  

Do you think patients should consider a second opinion consult with a specialist?

Dr. Westin:                 

It sometimes is appropriate. Other times, there’s not a lot of time. If treatment’s needed right away, you don’t want to get sicker because you’re waiting for seeing somebody two states over and it takes two weeks to get there. Sometimes you want to start treatment and get the second opinion after you’ve got the fire put out. But the second opinion usually gives more peace of mind than actually changing treatments. But if you’ve got that thought of, “I’m not so sure this is what I’d like to do,” or, “I’d like to get more information,” a second opinion may be very appropriate.

Katherine:                  

Okay. So, to close, Dr. Westin, what would you like to leave the audience with? Are you hopeful?

Dr. Westin:                 

I am very hopeful for the future for how we can beat DLBCL. We currently are curing the majority of our patients. We’ve got new weapons which look incredible and are continuing to help more and more people. But the main engine that we do help more people – the main engine that we make progress is clinical research through clinical trials.

I think this is something that we don’t want to rely on 1970s chemotherapy as we’re getting into the 2030s, and 2040s, and 2070s. This is something that we should be able to improve upon and to move beyond. And the only way we do that is through clinical trials. So, please do ask your doctor about what clinical trial might be right for you and don’t presume that a trial is something that’s experimental or something that’s not safe or not good for me. That’s how your treatments that we’re talking about today were originally discovered was through clinical trials. So, the future is bright. We’re helping a lot of people. And we can do more and do better in the future.

Katherine:                  

Thank you so much for taking the time to join us today, Dr. Westin.

Dr. Westin:                 

Thank you for having me.

Katherine:                  

And thank you to all of our partners.

Please continue to send in your questions to question@powerpatients.org and we’ll work to get them answered on 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 being with us today.

DLBCL Treatment Decisions: What’s Right for You?

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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.

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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.