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Is the COVID Vaccine Effective for CLL Patients?

Is the COVID Vaccine Effective for CLL Patients? from Patient Empowerment Network on Vimeo.

Is the COVID vaccine effective for chronic lymphocytic leukemia (CLL) patients? Dr. Paul Barr shares insight about mRNA-based COVID-19 vaccine effectiveness in CLL patients – both for those in remission and those in active treatment.

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

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An Expert’s Perspective on CLL Research Advances

Transcript:

Katherine:

I understand that researchers have been looking into whether the COVID vaccination is as effective in people with CLL. What can you tell us about that? The research?

Dr. Barr:

Sure. Everyone knew this was going to be an important question. We’ve known for a long time that riff CLL responses to vaccines in general aren’t as good as some of the normal population. So, there’ve been a whole host of studies over the years where patients didn’t quite respond as well to flu vaccines or pneumonia vaccines. Nonetheless, we typically recommend standard vaccinations, because there’s can be some degree of response. And our testing isn’t always perfect in terms of how well vaccines work.

So, when it typically, is felt to be a relatively safe procedure, is something we typically recommend.

More recently, we looked at studies on the shingles vaccine, and actually that works better than perhaps the flu shot, for example. Because patients probably were previously exposed to that virus earlier in life when they get vaccinated. So, recall response, which is a little bit easier for the immune system.

So, that brings us up to the COVID vaccines, which is obviously critically important ever on everyone’s mind. And the data’s still early. But what we’ve learned so, far is that, like what we might have predicted, our patients, the CLL patients don’t respond as well to the mRNA-based COVID vaccines.

So, in the media we saw, in the larger 20- and 40,000 patients studies that maybe, 95 percent of patients didn’t experience infection. It looks like in the general population, those vaccines work very well. In a cohort of 160, some CLL patients who are vaccinated early on in Israel, it looked like maybe about 40 percent of patients responded.

For the patients who hadn’t previously been treated but had measurable CLL, maybe about half of patients responded adequately in terms of generating antibodies. So, kind of a flip of a coin. For patients who have been treated and were in remission for more than a year, we’ll say the responses were better, maybe 80 percent or so.

For patients who are on active treatment, even our novel treatments, like the BTK inhibitors or venetoclax (Venclexta), the BCL-2 inhibitor, the responses were pretty poor, 18 or so percent.

So, you can see for patients with active disease, their responses are impaired. For those that are in remission, a little better. For those who are on active treatment, the antibody responses aren’t very good. So, I honestly think this is important information, but tell patients, don’t lose hope.

It’s still important to take the precautions. Some degree of wearing masks and social distancing. They will be better protected if their friends and family around them are vaccinated, and they still may respond to some degree. It’s not like the vaccines aren’t working at all. It’s just that the responses aren’t quite as good as the general population. So, again, another long-winded answer, but hopefully that helps patients understand some of the limitations in vaccinations.

But also that generally things are getting safer in that they still can venture out in society, but still have to take some precautions.

What is High-Risk CLL and How Is It Treated?

What is High-Risk CLL and How Is It Treated? from Patient Empowerment Network on Vimeo

What exactly is high-risk chronic lymphocytic leukemia (CLL), and how is it treated? Dr. Lyndsey Roeker discusses biomarkers that indicate high-risk CLL as well as treatment approaches that may be used for targeting specific subtypes of CLL.

Dr. Lyndsey Roeker is a hematologic oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Roeker here.

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Transcript:

Katherine:                  

We have an audience question. Mike wants to know, “What does it mean to have high-risk CLL?”

Dr. Roeker:                

So, great question, and the interesting thing is that I think the answer to that question is evolving. So, deletion of 17p, deletion of 11q, and TP53 mutation have historically been markers of more aggressive disease or unfavorable CLL. In the era where we only had chemo and immunotherapy, we know that patients had less great outcomes. We know that the treatments tended to not work as well, and patients had disease that tended to come back faster, and things like that.

That’s all evolving in the era of targeted agents. We have some indication that probably patients who have more aggressive underlying disease biology, meaning disease that’s going to behave less well, kind of regardless of what we treat it with, certainly may derive less benefit, meaning that the treatment will work for less long. That being said, these treatments are still really effective for our patients who have traditionally high-risk disease. So, I think it still remains to be seen, in terms of long-term outcomes and what to expect for patients that have these traditionally high-risk characteristics.

Katherine:                  

Let’s run through a few potential results so we can understand how you might approach each patient type. If someone has deletion 17p, what is the approach?

Dr. Roeker:                 

So, there are two totally reasonable frontline treatment options.

So, BTK inhibitors, which are – the current approved ones are ibrutinib and acalabrutinib, are completely a reasonable approach in the frontline setting, meaning the first treatment that someone gets, and those are pills that you take daily. For ibrutinib, it’s once a day. For acalabrutinib, it’s twice a day, for as long as they’re working. And the idea is, with this approach, you keep on those medicines, and they keep the disease suppressed. So, that’s the first option.

The second totally reasonable option is a combination of venetoclax (Venclexta) and obinutuzumab (Gazyva). So, venetoclax is a pill and obinutuzumab is an IV medicine, and the way that this was studied was a total of one year of therapy. So, from the time you start until you’re done with all of your treatments, that’s a one-year course. And the drugs have different side effect profiles, and depending on other medical problems, patient preference about, let’s just take a pill and that’s easy, versus the combination of pill and IV medicines, either can be a completely reasonable choice.

It just depends a lot on patient and doctor preference.

Katherine:                  

What about the TP53 mutation?

Dr. Roeker:                 

So, both of those treatment options seem to work very well for TP53-mutated patients. We had that discussion about the possibility of chemoimmunotherapy for a small minority of patients, and for patients with a TP53 mutation, using chemoimmunotherapy up front is probably not the correct answer. It’s better to go with one of the targeted drug approaches.

Katherine:                  

How would you approach each patient type, if a patient is IGHV unmutated?

Dr. Roeker:                 

So, IGHV-unmutated is the same discussion. Chemoimmunotherapy is probably not going to provide a durable, meaning it’s not going to last for a long time. We’re not going to achieve that potential cure. So, for those patients, either the BTK inhibitor approach, or the venetoclax/obinutuzumab approach is completely a reasonable one to take.

Katherine:                  

And if they’re IGHV-mutated?

Dr. Roeker:                 

IGHV-mutated patients who are young and don’t have a lot of other medical problems, that’s when we add in the third option of chemoimmunotherapy. For many patients, it’s not wrong to choose either a BTK inhibitor or venetoclax/obinutuzumab, but it does add in that third potential option of chemoimmunotherapy.

Katherine:                  

Are there other markers that patients should know about?

Dr. Roeker:                 

So, TP53 mutation status, FISH, and karyotype kind of gets you most of them. Some centers do additional next-generation sequencing of other genes that have been associated with higher-risk disease, though really understanding how to interpret those results still remains somewhat unclear, and that’s still an area of research that people are doing, to really understand what those other mutations really mean for people.

What Factors Impact CLL Treatment Options?

What Factors Impact CLL Treatment Options? from Patient Empowerment Network on Vimeo

What are the factors that impact chronic lymphocytic leukemia (CLL) treatment options? Dr. Lindsey Roeker notes important considerations that play a role in providing personalized care.

Dr. Lyndsey Roeker is a hematologic oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Roeker here.

Download Guide

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Transcript:

Katherine:                  

What about the impact of testing, overall? Why is it so important?

Dr. Roeker:                 

So, as we’ve moved from a disease that was really only treated with chemoimmunotherapy, to one that has targeted drugs available, knowing your IGHV mutational status really impacts what your frontline treatment options are. That’s the major therapy-defining risk factor. The other mutations help you know what to expect. So, for patients who have deletion of 17p or TP53 mutation, it’s possible that the treatments are going to, overall, work for a shorter period of time.

All that being said, every person is an individual, and it’s hard to predict exactly how long someone’s going to respond, from an individual basis. So, what I tell my patients is, “I could tell you what 100 of people with exactly your same disease would do, on average, but I can’t tell you exactly what’s going to happen for you. And that’s a journey that we’re going to take together and really understand over time.”

Katherine:                  

What are other important factors to consider, like a patient’s age, that can help them access the best treatment for their CLL?

Dr. Roeker:                 

So, age is important. Other medical problems is actually a very important consideration.

So, these medications have different side effect profiles and behave differently in different people. So, the BTK inhibitors, specifically ibrutinib is the one that we have the most data on, has cardiovascular side effects, so it can cause atrial fibrillation. It can cause high blood pressure. So, for patients who have preexisting heart disease, or preexisting atrial fibrillation that has been hard to control, or blood pressure that has been hard to control, for those people, I think adding in a BTK inhibitor can be a bit more of a higher risk situation than in somebody without those preexisting problems.

Venetoclax (Venclexta) is a pill that causes the cell to burst open rapidly, and it kills cells very quickly. Because of that, the major side effect is called tumor lysis syndrome, and tumor lysis syndrome is basically the cell opens up and all of the salt inside of it goes into the bloodstream.

And that salt can actually be really hard on the kidneys. So, for people who have kidney problems, venetoclax can be somewhat more challenging to use and just requires a higher level of vigilance. So, for patients who have preexisting kidney disease or the idea of a lot of monitoring and things like that, is more challenging. Then maybe the BTK inhibitors are a better choice.