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Emerging Treatments for Diffuse Large B-Cell Lymphoma

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Published on June 15, 2020

"There's always going to be a need for patients that have the disease come back, the relapsed-refractory patient population, and now we have many more options than we did," says Dr. Sarah Rutherford, a lymphoma expert from Weill Cornell Medicine.

With so many therapies receiving, or soon to receive, FDA approval for use in patients with aggressive or relapsed/refractory DLBCL, it is imperative that a patient confirms their diagnosis and seek out consultation with a specialist.

Watch as Dr. Rutherford and Patient Power Co-Founder Esther Schorr discuss diffuse large B-cell lymphoma and recent news from ASCO about current and emerging treatments.

This program is sponsored by Karyopharm Therapeutics. This organization has no editorial control, and Patient Power is solely responsible for program content.

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Transcript | Emerging Treatments for Diffuse Large B-Cell Lymphoma

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Esther Schorr:

Hi there. This is Esther Schorr with Patient Power, and I'm here today with Dr. Sarah Rutherford from Weill Cornell Medicine. She is a lymphoma specialist, and we are going to talk about some of the leading treatments and news that came out of the recent ASCO conference. Dr. Rutherford is a very special person in that she is a specialist in this area, and also, her commitment to this area of medicine really came from a personal experience. Her father had lymphoma, and that really triggered her enhanced commitment to this and to patient experience. So I want to welcome you, Dr. Rutherford, and thank you for taking time to speak with us today.

Dr. Rutherford:

Thank you. I'm happy to be here.

Esther Schorr:

Great. Thank you. So maybe first, tell us a little bit about what news there was at ASCO, especially about diffuse large B-cell lymphoma.

Dr. Rutherford:

I am happy to do that. I have a particular interest in terms of patient care and research in the more aggressive lymphomas, such as diffuse large B-cell lymphoma, which is the most common. And I had the privilege of working on a clinical trial with a number of other investigators across the country of a novel targeted drug, venetoclax (Venclexta), in combination with dose-adjusted EPOCH-R in aggressive B-cell lymphomas. We found that the particular dose of venetoclax, which is a Bcl-2 inhibitor, on a schedule of five days along with chemotherapy was well-tolerated in this patient population. Bcl-2 is either rearranged or overexpressed in many of the aggressive B-cell lymphomas and this drug, venetoclax, is a very promising agent to combine with chemotherapy in this patient population. And I look forward to forthcoming studies that combine these agents as well.

Esther Schorr:

What else is on the horizon for the treatment of diffuse large B-cell lymphoma? Anything else that you want to share?

Dr. Rutherford:

Well, I wanted to mention a bit more about the combination that we studied in the presentation that I had done at ASCO. And that's the venetoclax plus chemoimmunotherapy in diffuse large B-cell lymphoma. There is a trial being run through the Alliance for Clinical Trials called Alliance 51701, and this is looking at patients with double hit lymphoma and double expressor lymphomas. And these are particular groups that don't tend to do as well as some of the other patients with standard chemoimmunotherapy, which is either dose-adjusted EPOCH-R or R-CHOP, depending on the exact scenario. Jeremy Abramson is the PI of this study, and he and I worked very closely together on the study that I've already talked about. And this is looking at venetoclax in combination with those chemo-immunotherapies, particularly in those high-risk patient populations. So that's a clinical trial that's open and accruing now, and we're really excited to be able to offer that to patients. 

Another drug that I want to mention in combination with a novel agent is tafasitamab (MOR208), which is a monoclonal antibody against CD19. This is another protein that's expressed on the surface of B-cell lymphomas. Traditionally, the other monoclonal antibodies that we've used are targeted to CD20, so this is a novel area for targeted treatment. And that, in combination with lenalidomide (Revlimid), which is another targeted treatment that has been studied and FDA-approved in some types of lymphomas, which is a very promising drug. This combination is an emerging treatment option for people with relapsing refractory diffuse large B-cell lymphoma.

Esther Schorr:

So that's really interesting. It sounds like there's a lot going on in terms of new potential combinations. I know from talking to other patients who were following this, that there's been some talk about the use of selinexor (Xpovio) in combination for treating diffuse large B-cell lymphoma. What is that about?

Dr. Rutherford:

I actually have experience with that drug as well. I've been running a clinical trial here at Cornell with selinexor in combination with chemoimmunotherapy for people who have had a diagnosis of diffuse large B-cell lymphoma, but then have had it come back. So in that situation, the standard treatment is chemotherapy—there's not one standard treatment, but there are a couple options that we often use. One's called RICE. Another one's called R-DHAP. We have been looking at that in combination with a drug called selinexor, which has a novel mechanism. It's got a selective inhibitor of nuclear export, a very exciting mechanism. I've been investigating that drug, like I said, in combination with chemotherapy in the second-line setting for someone with diffuse large B-cell lymphoma who's had the disease come back.       

There have been some other exciting studies, and this is an emerging drug, which would be looking at this drug in a relapsed/refractory setting, so as a single agent. And it's an oral drug, so that's appealing to many patients to not have to come in for an infusional treatment. That's something that I'll be looking in the future to see as an option for these patients who desperately need more therapeutic treatment.

Esther Schorr:

So it really sounds like there's been a lot of research and potentially a lot of progress for patients, not only that are initially diagnosed, but it sounds like when people are in a more advanced stage or they've been treated and they need to be retreated, that that's a lot of what you're working on.

Dr. Rutherford:

Right.

Esther Schorr:

So are there other novel agents or treatment combinations that you haven't talked about? You've talked about a number of them, but anything else?

Dr. Rutherford:

I think I would be remiss to not mention the CAR-T cells as a new therapeutic option as of a couple of years ago. Essentially, these are currently FDA-approved for people who have had multiple lines of therapy and have progressed despite that. I think that there are interesting clinical trials that are ongoing, that are looking at autologous stem cell transplant versus CAR T-cell therapy. So I didn't mention that in my previous discussion, but the general algorithm for diffuse large B-cell lymphoma is frontline therapy is curative in about two-thirds of patients. If the disease comes back, they typically get second-line therapy with one of the regimens that I mentioned a bit ago, followed by autologous stem cell transplant if they have a good response to that second-line therapy, and they're fit for transplant.          

CAR-T cells have now become another line of therapy after that for either people who are not candidates for stem cell transplant, or do not have a good enough response to the second-line therapy or who relapse after stem cell transplant. So I think one emerging data point that will come out in the coming years is whether CAR-T cells can either replace autologous stem cells in certain cases or otherwise where they will fit in in this regimen. And also of interest will be combination therapies along with CAR T-cell therapy.

Esther Schorr:

Wow. So what this sounds like, in sum, to me is that there are a lot of options that weren't there a few years ago for people who are living with this disease. Well, people who are now living with the disease, and that you're working, you and your colleagues, are working on additional combination therapies and different types of therapy in order to extend life, quality of life, et cetera.

Dr. Rutherford:

Right, exactly.

Esther Schorr:

So hopeful message, for patients dealing with this?

Dr. Rutherford:

Right. I mean, just in the last five years or so, we have multiple more options. I didn't mention another drug called polatuzumab vedotin (Polivy), which is FDA approved in relapse and refractory diffuse large B-cell lymphoma as well. So I think we have a lot of novel drugs that are helping us to be able to improve outcomes of patients. And I think some of those may move up sooner. So for example, this venetoclax and chemotherapy combination may prove to be very effective in the frontline setting. But I think there's always going to be need for patients who have the disease come back, like I said, relapsed/refractory type patient population. And now we have many more options than we did even just five years ago. And I expect that five years from now, we'll have more and more, and that's really exciting for patients.

Esther Schorr:

That would be our hope too. So I have one last question. With all of this new information, if I am a patient dealing with this particular condition, are there any specific things that I should be asking my medical team, with that diagnosis, given everything that you've just said?

Dr. Rutherford:

That's a great question. I think one of the most important parts of lymphoma treatment is confirming that you have the most accurate diagnosis. So sometimes we have advocated for patients to either go, if they're not already in an academic center, to either go for a second opinion at an academic center, even if they are going to ultimately get treated closer to home, if they don't live near an academic center, or at least have their pathology reviewed somewhere else as a second opinion, to make sure that the diagnosis is accurate. We do our best to tailor treatment to an individual patient's tumor characteristics, and that information is evolving. So, for example, I mentioned the double hit lymphomas. Those are diagnosed based on particular chromosome abnormalities. So you want to make sure that your doctor is having those chromosome abnormalities checked.     

And I think we'll have more and more different ways of sub-categorizing diffused large B-cell lymphoma over time. There are a number of exciting papers that have come out in the last couple of years that are really breaking diffuse large B-cell lymphoma down into different categories that hopefully we'll be able to target specifically, and so that will improve the outcomes of those patients. So I think making sure that the pathologic assessment is done early is one of the most important parts.

Esther Schorr:

Wow. Well, Dr. Rutherford, thank you so much for sharing your time and your expertise with us and with the patients, especially the patients who are listening in to this. We all wish you well in the research that you're doing, and we thank you for the treatment that you already give to patients that are dealing with various forms of lymphoma.

Dr. Rutherford:

Thank you, Esther.

Esther Schorr:

This is Esther Schorr from Patient Power, and I just want to let you know, as I always do, that knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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