Tag Archive for: zanubrutinib

CLL Research Highlights: What Should Patients Know About?

CLL Research Highlights: What Should Patients Know About? from Patient Empowerment Network on Vimeo.

What should CLL patients know about recent research updates? CLL expert Dr. Adam Kittai shares recent research highlights, including updates on BTK inhibitors, BCL-2 inhibitors, and monoclonal antibodies.

Dr. Adam Kittai is a hematologist and an assistant professor at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Kittai, here.

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Transcript:

Katherine:

I understand that CLL researchers met recently at the annual American Society of Clinical Oncology meeting, also known as ASCO, to share their research. Are there highlights from the meeting that patients should know about?  

Dr. Kittai:

Yeah, so this time of year, there are two main conferences actually that are very important to the CLL groups at large, as well as the oncology community. So, there’s ASCO and then there’s EHA, the European Hematology Association. And in general, there was a lot of exciting things at both of these conferences. 

In CLL, we have two main treatments that we’re really focused on. One is called the BTK inhibitors, which is ibrutinib, acalabrutinib, and zanubrutinib that you may have heard about. And the other treatment regimen is called venetoclax, and that’s usually paired with something called obinutuzumab. So, right now we’re either using the BTK inhibitors or the venetoclax as our frontline therapies. And typically, when patients progress on either one of those treatments – their disease gets worse – we switch to the other one. 

And so, what I’m getting to be that right now, that paradigm of starting with one therapy – the BTK inhibitors or the venetoclax – and then switching to the other, or vice versa, is being challenged. How that’s being challenged is combining the two medications together to see if combining them together is better than giving them sequentially. So, I think this is the primary research that’s being looked at in the world of CLL and we got some updates to show that the combination of the BTK inhibitors, plus the venetoclax, is looking quite good. It’s looking like it’s inducing deep remissions in some of our patients.  

Some of the challenges here though that we still need to figure out is that a lot of these combinations are leading to more toxicity. So, ultimately, I think we’re going to have a discussion about who is the appropriate patient for the combination, as opposed to giving it sequentially. 

There’s also a lot more research going on, looking at what we call randomized trials, which we’ll get to in a second, to determine if the combination is better than giving it sequentially. Right now, we just have what we call single-arm studies that kind of show safety and how well the trial works. But really, the definitive clinical trials – and once again, we’ll get to this a little bit later – are going to be randomized study where we randomize patients to the combination versus the sequential therapy to determine if doing it together is better than doing it sequentially.  

So, I would say that this new treatment paradigm of combining our two main treatments up front is looking quite good. We’re worried about some of the toxicities when we combine these medications, and we’re still not quite sure if combining them is the right approach, if it actually is superior to giving them sequentially. So, I think that’s the name in research right now for CLL, whether or not combination therapy is better than sequential therapy. The jury is still out, but some of the new data we saw was exciting. 

Katherine:

So, how can patients stay up to date on research like this as it develops? 

Dr. Kittai:

Yeah, great question. So, for one, you can talk to your physician. A lot of the physicians will go to either ASCO or the European Hematology Association and be able to come back with some of this data to share with their patients. And then also, there’s a lot of smaller conferences that local oncologists will go to get highlights from these particular conferences, where they also will come back to the patient to let them know some of this highlighted research. I think that’s probably the easiest way for patients to get access to this research. And Google’s our friend, right? And so, a lot of things are available on Google if you know where to look for them. 

Exciting Advances in Waldenström Macroglobulinemia (WM) Treatment

Exciting Advances in Waldenström Macroglobulinemia (WM) Treatment from Patient Empowerment Network on Vimeo.

What new therapies are on the horizon for patients with Waldenström macroglobulinemia (WM)? Dr. Shayna Sarosiek from Dana-Farber Cancer Institute reviews promising developments in WM treatment, including immunotherapy and BTK inhibitors.

 Dr. Shayna Sarosiek is a hematologist and oncologist at the Dana-Farber Cancer Institute where she cares for Waldenström macroglobulinemia (WM) patients at the Bing Center for Waldenstrom’s. Dr. Sarsosiek is also Assistant Professor of Medicine at Harvard Medical School. Learn more about Dr. Sarosiek, here.

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Transcript:

Katherine:

What are you excited about when it comes to Waldenstrom’s research? 

Dr. Sarosiek:

So, there a couple of things that I find really exciting right now. One thing in particular is currently for treatment for Waldenstrom’s, we often use BTK inhibitors. So, the group of medications that includes zanubrutinib (Brukinsa), ibrutinib (Imbruvica), acalabrutinib (Calquence). And that class of medications has really revolutionized treatment for Waldenstrom’s. But sometimes patients become resistant to those medications. And there’s a new group in that same class of what’s called BTK inhibitors.  

And those are non-covalent BTK inhibitors. And those drugs actually work often for patients who progress on initial therapy with ibrutinib or zanubrutinib. So that really, I think is game changing. There are some early Non-Covalent BTK inhibitors that are in trials. And I really think it’s going to lead to use of those medications very commonly in the future for Waldenstrom’s. So, that I think is exciting to have a next oral therapy to go to after progression on the current therapies. I’m also excited about new combinations that are being tried in Waldenstrom’s.  

So, using combinations of different oral therapies together that would offer deep responses and also offer a time-limited therapy. Because right now many of our treatments are given indefinitely. And so, offering a limited therapy. So, I think that, and there are many other things I could go on for a long time about this. But there are many things that I think are really exciting and we’re going to be changing the field in the coming years. 

Katherine:

Dr. Sarosiek, what is immunotherapy? Could you define that and also, how does it work to treat Waldenstrom’s? 

Dr. Sarosiek:

So, immunotherapy includes many different types of medications. But these are all medications that either use the patient’s immune system or use something from the immune system, like an antibody to help fight off a cancer. And this plays a huge role currently and I think it will continue to in the future. So, probably the most common immunotherapy that patients are familiar with, with Waldenstrom’s now is rituximab (Rituxan). So, that’s a monoclonal antibody.  

And that’s used in many combinations in Waldenstrom’s and is a very important therapy currently. And that antibody is essentially just goes into where the cancer cells are located and attacks that type of cell.  

But the other immunotherapies that are up and coming – which I think are important for patients to know about – one is CAR-T cell therapy. So, a lot of patients ask me about that. and that’s essentially, a T cell is part of the immune system that every patient has. And what CAR T-cell therapies do is patients can collect from their bloodstream – the physicians can collect T cells and then they modify those T-cells in a way so that they’ll recognized the cancer and attack the cancer.  

And so then, those T cells are given back to the patient and then that T  cell can go and work with the patient’s immune system to destroy the cancer. And that’s been very successful in a lot of other cancers and is being used in Waldenstrom’s now. And I think we’re going to be learning a lot about that and it’s going to be an important part of the future with immunotherapy involved in Waldenstrom’s. Another therapy similar is something called BiTE therapies. So, Bispecific T-cell engagers.  

So, that’s essentially two antibodies together. One antibody kind of pulls in the cancer cell and one antibody pulls in the immune system. So, when that treatment is given to patients it kind of brings the immune system close to the cancer cells. So, your own immune system can help fight off the cancer. So, those are just kind of two of the newer immunotherapies that are up and coming that I think will play an important role in the future in this disease. 

Katherine:

Who is this treatment right for? 

Dr. Sarosiek:

Immunotherapies in general currently we’re using them – currently immunotherapies are being used in patients who have had a relapsed disease. So, they have already had current available therapies, like BTK inhibitors or rituximab. And there are clinical trials that can use CAR-T cell therapy. And there are up and coming trials with BITE therapy. So, right now it’s being used in their relapse setting. But as we learn more about it, it’s possible those we moved earlier on to patients who are earlier in their disease course. 

Katherine:

What kind of side effects should patients be aware of? 

Dr. Sarosiek:

So, the side effects can vary depending on what the therapy is. So, patients who are getting rituximab, the currently available immunotherapy, patients can have infusion reactions. So, as your body is kind of getting used to that monoclonal antibody coming in, you can have a reaction. And in that case, we have to stop the infusion, wait for the side effects to settle down, and then restart.  

Katherine:

What type of side effects would they be? 

Dr. Sarosiek:

So, side effects from rituximab infusions can really vary. In some patients it can be similar to an allergic reaction. So, let’s say itchy throat or a rash or hives. Sometimes it can be pain in the chest or the back or trouble breathing. So, they can really vary. But most of the time, those can – when the infusion is stopped, we can give patients medications like Benadryl or Tylenol to help with symptoms. And then we can restart the Rituximab at a lower rate. And that lower rate allows the patient’s body to kind of get used to the medication and continue on the treatment. So that’s generally the things we watch for with Rituximab. 

CLL Treatment and Research Update: News from ASCO 2021

CLL Treatment and Research Update: News from ASCO 2021 from Patient Empowerment Network on Vimeo

What’s the latest chronic lymphocytic leukemia (CLL) treatment and research news out of the American Society of Clinical Oncology (ASCO) 2021 meeting? Dr. Paul Barr shares study results and explains how they could impact CLL care.

Dr. Paul Barr is Professor of Hematology/Oncology at University of Rochester Medical Center. Learn more about Dr. Barr, here.

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Transcript:

Katherine:

I’m Katherine Banwell, your host for today’s program. Joining me is Dr. Paul Barr. Dr. Barr, would you please introduce yourself?

Dr. Barr:

Sure. Hi, Paul Barr from the University of Rochester. Glad to be here.

Katherine:

Thank you so, much. Cancer researchers came together recently to share findings at the annual American Society of Clinical Oncology meeting, also known as ASCO. Is there news from the meeting that CLL patients should know about?

Dr. Barr:

There is. It seems like at every major meeting, we have a potentially practice-changing dataset that we like to scrutinize and talk about. This ASCO is no exception. I think probably the most impactful abstract was a report.

The first time we’ve seen the results from a study that was called The ELEVATE Relapsed Refractory Study. This was a randomized trial, enrolling previously treated CLL patients who had high-risk disease and randomizing them to two of our very important BTK inhibitor treatments.

Half the patients got acalabrutinib (Calquence), and the other half received ibrutinib (Imbruvica). And both groups were treated until the drug essentially either stopped working, the disease became resistant or was stopped for side effects. So, this was a study we have waited on the results for a long time given that we don’t often see these randomized studies comparing two such active agents. And the results showed us that both drugs work really almost equally as well.

The progression-free survival or the roughly the average amount of time patients are taking the drug was just over three years, 38 months in both arms. So, they really work very well and equally as well. But we did see less side effects with the acalabrutinib. And one of the most important side effects that the study was powered around was, atrial fibrillation or flutter.

There was less AFib or less new AFib in patients that were treated with the acalabrutinib. There was also less minor bleeding, arthralgia, diarrhea. So, a number of, perhaps less severe type side effects, were less common. There was more headache and more cough in the acalabrutinib-treated patients. But I think overall, most of us took from this abstract that both drugs work exceptionally well.

And overall, are very well tolerated treatments although there does look to be lower rates of a number of important side effects with acalabrutinib.

Katherine:

Dr. Barr, is there any other news from the conference that patients should know about?

Dr. Barr:

There is. I’ll give you a couple other additional findings. One was an update of a study, we’ve seen the results before. It’s sort of a partner study to the one I just mentioned. It was called The ELEVATE TN or ELEVATE Treatment Naive Study.

These were previously untreated patients, treated with an old standard, randomized study where the patients received either chlorambucil-based therapy (Leukeran). It was combined with a CD20 antibody obinutuzumab (Gazyva). The second arm was single agent acalabrutinib and the third arm was acalabrutinib plus obinutuzumab. Not surprisingly both of the acalabrutinibs continue to perform very well. The treatments work much better than chlorambucil. But now, we have four-year data. And that’s important for us to really understand what to expect as time goes on.

And I think that the major take-homes are that, acalabrutinib continues to work very well in the first-line setting. There is a hint that acalabrutinib, I’m sorry, that obinutuzumub may prolong the remissions, which is a little bit surprising to us.

But again, small differences in the study weren’t powered to really look at that comparison. And also, the major take home from that dataset is that the safety still looks very good at four years for the patients receiving acalabrutinib. So, I think that continues to shape our practice. And I think the last dataset or abstract to comment on, was one actually we saw at a different meeting at the European Hematology Association meeting, EHA. And this was another randomized study comparing two different BTK inhibitors in relapsed CLL patients.

This one compared ibrutinib and zanubrutinib (Brukinsa). Like acalabrutinib, zanubrutinib is another more specific BTK inhibitor. And when you compare it to ibrutinib and perhaps somewhat similarly to The ELEVATE Relapsed Refractory Study in this zanubrutinib-ibrutinib comparison, so-called ALPINE study, we saw similar efficacy.

Zanubrutinib actually looked like it performed a little better than ibrutinib, but also again here, lower rates of side effects. So, the theme continues for the more specific BTK inhibitors. They seem to work just as well, maybe a little better in some respects, compared to Ibrutinib and somewhat lower rates of side effects. So, when you put it all together, all of the BTK inhibitors work exceptionally well.

We have varying degrees of follow-up and confidence. We have the most follow-up in our ibrutinib treated patients so, we know what to expect for patients six, seven years out after being on ibrutinib.

But we’re now seeing in these earlier studies that lower rates of various toxicities for the newer more specific BTK inhibitors. So, kind of a long-winded answer to your simple question, but hopefully that shows how the new and emerging data continues to shape how we take care of patients.