Tag Archive for: CD20

What’s the News on Follicular Lymphoma and Bispecific Antibodies?

What’s the News on Follicular Lymphoma and Bispecific Antibodies? from Patient Empowerment Network on Vimeo.

What should follicular lymphoma patients know about bispecific antibodies? Expert Dr. Kami Maddocks from The Ohio State University discusses treatment and research updates on bispecific antibodies.

See More from START HERE Follicular Lymphoma

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Transcript:

Lisa Hatfield:

So regarding clinical trials right now, are there any clinical trials that you are conducting or that you’re particularly excited about for patients that they might want to ask their providers about?

Dr. Kami Maddocks:

Yes, so we’re also looking at opening a trial for frontline follicular lymphoma that looks at the use of bispecific antibodies. So I think that’s very exciting, because in general, it’s a well-tolerated therapy. And I think if it gives us a chance to produce very good outcomes, but without the toxicity of chemotherapy in the frontline setting, that to me is super exciting for patients.

We’re also looking at different bispecific antibodies. So they currently approved one target CD20. We have a CD19-targeted bispecific antibody that I also think is exciting to look at the potential for different targets because then once a patient has had one, you’re targeting something different, and the thought is that they might still be able to respond to a different one.

Lisa Hatfield:

Yeah. So with bispecifics then, is that continuous therapy, or is that limited duration therapy?

Dr. Kami Maddocks:

It actually depends on the bispecific. So in follicular right now, the one approved is for a limited duration. When you look at a few of the others that have been approved and other lymphomas that are being studied in follicular lymphoma, there’s a little bit of a variation between continued treatment and limited-duration therapy. I think what’s exciting about a lot of the combination studies is they are more looking at a defined period of time with the combinations.

Lisa Hatfield:

Which I’m sure a lot of patients love to hear that. Limited duration, there’s an end to this possibly, so yeah. 

Dr. Kami Maddocks:

Yeah. Nobody wants to be on treatment forever. 


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Relapsed/Refractory Follicular Lymphoma Treatments and Bispecific Antibodies

Relapsed/Refractory Follicular Lymphoma Treatments and Bispecific Antibodies from Patient Empowerment Network on Vimeo.

What can relapsed/refractory follicular lymphoma patients expect for current and future treatment options? Expert Dr. Sameh Gaballa explains what treatments are currently available and ones that are being studied for the future.

Dr. Sameh Gaballa is a hematologist/oncologist specializing in treating lymphoid malignancies from Moffitt Cancer Center. Learn more about Dr. Gaballa.

See More from START HERE Follicular Lymphoma

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Transcript:

Lisa Hatfield:

Another patient is asking if you can speak to emerging treatment options for patients with relapsed/refractory follicular lymphoma?

Dr. Sameh Gaballa:

Yeah. So the field of follicular lymphoma is changing rapidly. I always tell patients that sometimes the best treatment is actually on a clinical trial because those are going to be the next generation of treatments that are going to get approved in the next few years. But right now we have the most effective therapy really is CAR T-cell therapy. CAR T-cell therapy by far is the most effective treatment we have at this time. It’s approved for patients who have had two or more lines of prior therapies. We also are investigating this. I actually have a trial here at Moffitt where we’re looking at CAR T-cell therapy as early as in the second line, in patients who have what we call the high-risk ones, the POD24. So a patient with POD24 follicular lymphoma relapsed in less than two years. We have a trial to investigate the role of CAR T-cell therapy in this setting. The other very promising group of treatments, again, is bispecific antibodies, again, currently approved in the third line, mosunetuzumab-axgb (Lunsumio).

But there are others coming up and have data on epcoritamab-bysp (Epkinly), as well as a lot of other bispecifics, as well as combinations. I mean, epcoritamab-bysp has also data presented with combination with lenalidomide. And right now, the follow-up duration is not very long, but so far, it looks extremely promising with very high response rates. So those also might be coming very soon. And, of course, once something works in the relapsed/refractory setting, we start looking at earlier lines of therapy. And actually, we’re now looking at trials in the first-line setting with some of these agents as well. Tazemetostat (Tazverik) is a pill. It’s also approved in the third-line setting, but we’re also investigating it. We have a trial here where we’re looking at combining it with standard rituximab (Rituxan), lenalidomide (Revlimid), so tazemetostat plus rituximab, lenalidomide as early as in the second line. So that also is interesting. And as I mentioned before, BTK inhibitors currently being looked at in trials might also have a role in follicular lymphoma very soon.

Lisa Hatfield:

And this patient is asking about the significance of bispecific antibody treatment. And you touched on that a little bit. It looks like she’s also asking if there are specific genetic or molecular markers that can predict a patient’s response. And if I try to translate that, maybe she might be asking about targeted therapy.

Dr. Sameh Gaballa:

Yeah, so bispecific antibodies and CAR T-cell therapy, they target something called CD, either CD19 or CD20, and that’s almost universally expressed on B cells. So most of your follicular lymphoma patients are going to be expressing CD19 or CD20. Tazemetostat is the pill that I talked about. It inhibits an enzyme called EZH2. Some patients have an EZH2 mutation where it seems to work very well. However, tazemetostat also works in patients who don’t have that mutation. So that’s why it’s not very important to check for the mutation.

It seems maybe it works better in patients who do have the mutation, but it does work as well in patients who do not have that mutation. So unlike other malignancies and other cancers, biomarkers are not yet driving a lot of our treatment decisions in follicular lymphoma as of right now.

Lisa Hatfield:

How exactly do bispecific antibodies engage the patient’s immune system to target and eliminate follicular lymphoma cells?

Dr. Sameh Gaballa:

So bispecific antibodies are a very interesting class of medicines. It’s an antibody that has two ends to it. So one end would target the patient’s own immune cells, meaning that they would attach the antibody to the patient’s own immune cell and then the other end of the antibody engages the cancer cell. So it’s basically hand-holding the patient’s own immune system to go and kill the cancer cell. And this is not just in lymphoma. It’s looked at in multiple myeloma as well, approved therapies there. And a lot of other cancers, we have bispecific antibodies being developed in clinical trials right now. 


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Can CLL Remission Occur With Rheumatoid Arthritis Drug Treatments?

Can CLL Remission Occur With Rheumatoid Arthritis Drug Treatments? from Patient Empowerment Network on Vimeo.

Is it possible for chronic lymphocytic leukemia (CLL) remission to occur from rheumatoid arthritis treatments? Expert Dr. Ryan Jacobs explains what he’s observed in his CLL patients who also have RA and take RA treatments.

Dr. Ryan Jacobs is a hematologist/oncologist specializing in chronic lymphocytic leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

See More from START HERE CLL

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Transcript:

Lisa Hatfield:

Do any rheumatoid arthritis medications help prevent CLL from returning after treatment with FCR?

Dr. Jacobs:  

I do have a fair number of patients that have rheumatologic conditions and some with rheumatoid arthritis. There are some approvals there, and I in no way pretend to be an expert in rheumatoid conditions. But I do know that there happens to be some agents that are monoclonal antibodies directed against CD20 used to treat some rheumatoid conditions. So I do have some patients that are on drugs like rituximab (Rituxan) to suppress their rheumatoid condition and help prevent recurrences.

And then kind of two birds, one stone also are keeping their CLL in a clinically asymptomatic remission, I’m sure I would say, or stable disease. And it comes with the known risk for long-term antibodies, that there are some increased infections there that was particularly concerned during COVID, the worst parts of COVID. But yeah, so there are some potential treatments like that.


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What Is CD5 Expression in CLL?

What is CD5 expression in CLL? from Patient Empowerment Network on Vimeo.

Chronic lymphocytic leukemia (CLL) patients display a different CD5 expression than some other blood cancers. Watch to learn about CD5 expression and how monitoring plays into CLL patient care.

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Transcript:

The protein of CD5 is abnormally expressed (or displayed) in T cells and/or in B-1a B cells in chronic lymphocytic leukemia (CLL) and is often referred to as a marker. The small CD5-positive B lymphocytes multiply and accumulate in a CLL patient’s blood, bone marrow, and secondary lymphoid tissues and then create the condition of CLL. Though some blood cancers show as CD5-negative status, CD5 is shown as overexpressed along with CD19 and CD23 combined with weak expression of CD20 and CD79b in CLL patients.

Recent research studies looking at different CD markers including CD5 show that monitoring of CD expression changes over time can help more accurately determine prognosis for CLL patients. 

Dr. Jennifer Woyach:

“So, there is kind of a code of these markers on the surface of all of your blood cells that can tell what type of cells they are. So, for CLL in particular, we’ll see that the cells express some of the normal markers we would see on a normal B lymphocyte.

Things like CD19, CD20, CD23. But they also express a marker called CD5, which is found on normal T lymphocytes but shouldn’t be found on B lymphocytes.

And so, this collection of surface markers can make the diagnosis of CLL. Sometimes, we do need to do extra studies like a bone marrow biopsy or a lymph node biopsy. But oftentimes, those are not necessary at the time of diagnosis.”

As always, check with your CLL specialist if you have more questions about CD5 expression in CLL.

CLL Patient-Expert Q&A

Dr. Nadia Khan | CLL Patient-Expert Q&A from Patient Empowerment Network on Vimeo.

Is CAR T-cell therapy a cure for chronic lymphocytic leukemia (CLL)? What specific lab tests will I need to get a second opinion? CLL expert Dr. Nadia Khan answers questions from CLL patients and families. 

Have a question for a future Patient-Expert Q&A Email us: question@powerfulpatients.org with subject line: CLL Patient-Expert Q&A 

See More from START HERE CLL

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Transcript:

Mary Leer:

Dr. Khan, first of all, thank you for being part of this program. 

Dr. Nadia Khan:

Thank you so much for inviting me to participate.

Mary Leer:

We have a question from Larry about side effects. Larry says: I’ve been fighting side effects with each medicine. Will the correct answer for side effects in CLL always be to stop the medicine? 

Dr. Nadia Khan:

Larry, thank you for your question. It is an excellent one, and this is something that we encounter on a very regular basis in CLL patients who are on targeted therapies. The side effects occur frequently in patients taking BTK inhibitors, in patients taking PIK inhibitors, and we have some side effects reported on BCLT inhibitors as well, typically side effects on all of these targeted therapies can be managed with either dose reduction or supportive therapies, and we don’t necessarily have to stop a medication due to a side effect that is encountered, and of course, it would depend on the type of side effect and the severity of the side effect before deciding to pause therapy for a time or to dose reduce or add other medications to help.

Mary Leer:

Sarah has a question about side effects. How can I tell if side effects are from CLL, my medicine, or just a part of aging? 

Dr. Nadia Khan:

Thanks for that question, Sarah. It can be a challenge to tease out the cause of any given complaint, whether the symptom is due to underlying other medical conditions, the medications a patient is on, their CLL therapy, their CLLl itself is something that we find to be challenging, and it can often be a process of elimination and understanding when side effects started and how they are related to the known side effect profile of a therapy is often a starting point. Depending on the side effect, we may decide to institute a treatment holiday, and if the side effect improves or resolves during the treatment holiday, it’s more clear that the side effect is due to the medication in question. If the side effect persists during that period of time, then it’s more likely to be due to something else.

Mary Leer:

George asks, are there any long-term side effect risks for CLL patients? 

Dr. Nadia Khan:

That’s a great question, George. It really would depend on the therapy being instituted and when in the chemoimmunotherapy era for CLL patients, we have a very different perspective of what short-term and long-term side effects were and are for those patients who have been treated with chemoimmunotherapy. For patients treated with targeted therapies and immunotherapy combinations today, there tends to be fewer serious long-term side effects when looking at the various drug classes. For example, BTK inhibitors, there is a risk of atrial fibrillation that remains constant throughout the course of therapy, and if a patient is on therapy for one year or 10 years, they can develop that particular side effect. High blood pressure can be significant with BTK inhibitors as well, and that risk also tends to be stable. In terms of infection risk, there is relative immunosuppression with all CLL therapeutics, and so our concern, more recently has been focused on COVID infection, serious bacterial and viral infections tend to be less frequent, we don’t institute prophylaxis for those infections because they tend to be so few and far between in the patients that we’ve treated. 

Mary Leer:

Thank you, Dr. Khan. Here’s a question from Richard:  I am a CLL patient currently on “watch and wait.”  When is the right time and what tests should have been performed before seeing a CLL specialist? 

Dr. Nadia Khan:

Richard, thank you for your excellent question. There are a number of tests with respect to CLL that help us to prognosticate more accurately, and those would include either a FISH panel, fluorescence in situ hybridization for CLL which identifies this common amplification and deletions that have been described in CLL. Additionally, an IgVH mutational test and a TP53 sequencing test would be the three basic prognostic tests used to identify what kind of CLL a patient has. This testing should be repeated at any point wherein a patient is changing therapy or at any point where there’s a change in the clinical status of the patient. Outside of these standard tests, there are other molecular tests that can be ordered and are commercially available for use… For use by clinicians. These molecular tests can also identify changes within the CLL that can help to prognosticate at this time, outside of the standard tests that I mentioned to you, there are no proven benefits to other testing, but the results of additional testing can just really help inform your clinician about the likelihood of you needing treatment in the near future and the likelihood of response to therapy. 

Mary Leer:

This question comes from Laurie. How common is it for CLL patients to develop a second gene mutation? 

Dr. Nadia Khan:

Laurie, Thanks for that question. It is not common for most call patients to have significant alterations in the genetic landscape of the CLL. With that being said, there are a few notable exceptions for CLL with TP53 dysfunction or complex cytogenetics, there is a higher likelihood that there will be genetic instability in those CLL clones. Therefore, it’s important to retest for changes if there is a change in the biology of the CLL, if there is a progression on therapy, for example, or at the time when a new therapy is planned.

Mary Leer:

Yolanda’s question is, what is CAR T therapy and who is eligible? 

Dr. Nadia Khan:

Thank you, Yolanda. This is a question that I get asked very frequently. CAR-T therapy is an exciting cellular therapy that has been FDA-approved in a number of lymphomas, and it is currently not FDA-approved for patients with CLL. So at this time, CLL patients can receive CAR-T therapy in the setting of a clinical trial only, and it is typically reserved for those patients who have progressed or relapsed after multiple lines of therapy and for whom there is no alternative therapy for consideration. Often, it is considered in the context of the clinical trial prior to the use of allogeneic stem cell transplant, because the results of allo transplant and CAR-T seemed to be fairly comparable. CAR T therapy, however is much better tolerated than allo transplant, both of these modalities are very rarely employed for our CLL patient today because of the very effective targeted therapies and immunotherapies that we have to use. 

Mary Leer: 

Dr. Khan, Chuck’s question is, what are the side effects of CAR-T cell therapy? 

Dr. Nadia Khan: 

Thank you, Chuck. For your excellent question, CAR-T-therapy is associated with two main types of side effects, one is Cytokine Release syndrome or CRS, which happens within the first two weeks of receiving CAR cells, and that can manifest as fevers, chills, a drop in blood pressure, shortness of breath, and the requirement of oxygen. When that happens to patients, there are medications that are given to help improve those cytokine-mediated events. Another major side effect with CAR-T therapy is neurotoxicity, which also happens within the first 14 days in some patients who receive CAR therapy, and that can manifest as anything from a headache to more concerning confusion, seizures and coma. CRS happens commonly in patients who receive party therapy and is usually managed very successfully with anti-inflammatory therapies given intravenously in the hospital and can be used for patients even who get outpatient CAR-T therapy.

Dr. Nadia Khan: 

When patients do suffer with neuro toxicities, intravenous therapies are also employed to combat that, and when necessary, patients might require escalation to an intensive care setting when these toxicities are very severe.

Mary Leer: 

Dr. Khan, is CAR T therapy a cure for CLL? 

Dr. Nadia Khan: 

Thank you for your question, Bernard. CAR-T therapy has been curative for a minority of patients who have been treated with CARs on clinical trials, and unlike other lymphomas In CLL, there hasn’t been an FDA approval as yet for CAR-T therapy, and we are hopeful for that to change in the future as CARs are modified and may potentially become more effective at eradicating the CLL and hopefully resulting in better side effect profiles and patients who do receive CAR-T therapy, the majority of patients who have received CARs in CLL studies have not had durable remission, unfortunately.

Mary Leer: 

Dr. Khan, what is conditioning therapy and why is it given prior to infusion of the CAR T cells?

Dr. Nadia Khan: 

Thank you, Samuel. Conditioning therapy is a course of – a briefer course of chemotherapy that’s given just prior to CAR-T therapy, really to prepare the body in a way to receive the CARs, and it makes the CARs more effective when there has been a level of immunosuppression to allow the CARs to expand more freely after they have been re-infused into a patient.

Mary Leer: 

Okay, here’s a question that Sandra asks, I’m preparing for CLL treatment, can I take my vitamins, herbs, or other supplements during treatment?

Dr. Nadia Khan: 

Thanks for that excellent question, Sandra. It’s so important to review all of your medications with your provider before starting any therapy during the course of your CLL treatment, drug interactions with herbals and over-the-counter medications can result in serious side effects, some over-the-counters and Herbals can inhibit the effectiveness of CLL therapy. So it’s important to discuss these with your provider on a case-by-case basis.

Mary Leer: 

Dr. Khan, here’s a question that I think many are probably thinking of right now, what tests do you give patients to see if CLL treatment is working?

Dr. Nadia Khan: 

Thank you, Jessica. During the course of CLL treatment and at the end of a time-limited treatment course, we’re assessing for responses, so as a patient is going through their treatment, we may decide to re-image to determine if there has been debulking of lymph nodes. And depending on the treatment that we’re administering and where the lymph nodes are located, we may decide to do imaging sooner or later, so for example, if there are palpable lymph nodes while a patient is on therapy, and we can measure these readily by physical exam in the clinic, we may not feel as compelled to re-image at an early time point, if there is valiantly or in large seen that is hard to palpate. And we want to understand if treatment is working after approximately three to four cycles of therapy, we would assess for a good response to treatment if clinically, it also does appear that patients are responding, and if there was any question as to respond, we would image at an earlier time point when patients are being treated with a Venetoclax [VENCLEXTA] based regimen and there is significant adenopathy or an enlarged spleen, we may reassess the size of lymph nodes and spleen during the course of Venetoclax [VENCLEXTA] ramp-up to determine if patients can be transitioned from inpatient to outpatient ramp-up.

Mary Leer: 

Dr. Khan, this is our final question. Karen asks, with many new therapies available, will watch and wait be redefined for CLL patients? 

Dr. Nadia Khan: 

What an excellent question, Karen. Currently, the strategy for CLL patients is to institute therapy when there is likely to be a benefit with the intervention, and there are studies that are ongoing looking at earlier intervention with oral therapy, and once we see the readout for patients with particularly high-risk features. I think it is possible that we’ll have an alternative strategy for those patients. Thankfully, our CLL patients live very long lives, and what we’ve come to see over decades of treatment experience with our CLL patients is that early intervention to date has not resulted in longer… Longer survival. So at this point, it’s not something that’s recommended, but we may have more information soon.

Mary Leer: 

Dr. Khan, thanks for joining us today and answering all of these questions for our audience. Just a reminder to our audience, please take the CLL-Patient-Expert Q&A survey following this webinar.

Mary Leer: 

Dr. Khan, before we end this program,  what are you optimistic about for the future of CLL? 

Dr. Nadia Khan: 

So I’m very optimistic about the future of CLL therapeutics, we’ve already come to see excellent responses that are very durable with time-limited targeted therapy and immunotherapy approaches. In the future, it is likely that we will be using a more personalized approach to treating any given CLL patient using their genetic and molecular profile to decide on their treatment strategy, a single-agent approach versus multiple targeted therapies to eradicate CLL clones. In the future will be looking at endpoints like minimal residual disease, as well as clonal evolution to help guide our treatment strategy for patients with CLL

What Is CLL and How Is It Diagnosed?

What Is CLL and How Is It Diagnosed? from Patient Empowerment Network on Vimeo.

What exactly is chronic lymphocytic leukemia (CLL), and what factors help determine a diagnosis? Dr. Jennifer Woyach explains how CLL originates and transforms, the tests involved in diagnosis, and shares a common misconception about CLL.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

See More From INSIST! CLL


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Transcript:

Katherine:                  

Well, Dr. Woyach, let’s start by understanding CLL. Would you briefly walk us through what CLL actually is?

Dr. Woyach:               

Sure. CLL is a cancer of the blood, the lymph nodes, and the bone marrow.

And it happens when a particular type of white blood cell called a B lymphocyte acquires genetic mutations and transforms into a cancer cell. And then, over time, those cancer cells continue to grow and divide. And they can cause symptoms such as enlarged lymph nodes if the cells get stuck in the lymph nodes and continue to grow there. It can cause a high white blood cell count, which usually doesn’t cause any symptoms but is one of the things that we see often in CLL. And then, it can also cause the bone marrow to not be able to produce normal cells because it can get so infiltrated or so full of CLL cells.

And this can cause things like anemia, which is lowering of the red blood cell count and thrombocytopenia, which is lowering of your platelet count.

Katherine:                  

What are the steps involved in reaching a diagnosis?

Dr. Woyach:               

CLL is an interesting disease because it’s one of the only cancers that does not require a biopsy of something for a diagnosis.

So, we can, actually, make the diagnosis of CLL based on the peripheral blood. So, just a blood draw in somebody’s doctor’s office. Usually, CLL is diagnosed in the asymptomatic stage. So, somebody goes to their primary care doctor, has blood drawn usually for another reason, and is found to have a high white blood cell count or sometimes even a fairly normal white blood cell count but a high percentage of lymphocytes. That certain type of cancerous white blood cell. So, the next step in the diagnosis then is something called peripheral blood flow cytometry, which is a specialized test where we look at the markers or antigens on the surface of white blood cells.

So, there is kind of a code of these markers on the surface of all of your blood cells that can tell what type of cells they are. So, for CLL in particular, we’ll see that the cells express some of the normal markers we would see on a normal B lymphocyte.

Things like CD19, CD20, CD23. But they also express a marker called CD5, which is found on normal T lymphocytes but shouldn’t be found on B lymphocytes.

And so, this collection of surface markers can make the diagnosis of CLL. Sometimes, we do need to do extra studies like a bone marrow biopsy or a lymph node biopsy. But often times, those are not necessary at the time of diagnosis.

Katherine:                  

When you meet with patients, Dr. Woyach, what are some common misconceptions that you hear about?

Dr. Woyach:               

I think the biggest thing that I hear, and granted I see a lot of patients after they’ve been diagnosed by someone, gone to see an oncologist and then, come to me after, but one of the common things that I hear is that somebody has told them along the way that they have the good type of cancer, which I think is not a very helpful thing to hear as a patient because, of course, no cancer is a good type of cancer.

I think it’s important to note that CLL is one that has a lot of treatment options and usually extended survival. But I think that’s one of the most common misconceptions that I hear.