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The Difficult Choices When Making CLL Treatment Decisions

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Published on June 5, 2020

Making treatment decisions can be a challenge for any chronic lymphocytic leukemia (CLL) patient. Patient advocate Carol Preston is joined by Dr. Jacqueline Barrientos to answer questions from CLL patients and care partners. Watch to learn expert answers about treatments, skin rashes and CLL, and more.

This program is sponsored by AbbVie, Inc., Genentech, Inc. and Adaptive Biotechnologies. These organizations have no editorial control. Patient Power is solely responsible for program content. 

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Transcript | The Difficult Choices When Making CLL Treatment Decisions

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.

Carol Preston:

Hello everyone, I'm Carol Preston. This is Patient Power, and welcome to Ask the Expert. CLL specialist, Dr. Jacqueline Barrientos will take your questions about CLL and the ever expanding landscape of treatments. For those of you who may not know me, I have been living with CLL for nearly 14 years and a second cancer since 2018. Now, the pandemic has certainly dominated our lives for these past months, but guess what? Cancer does not take a vacation and neither do treatments. We who live with CLL or who are newly diagnosed more than ever need to know what we are facing and how to handle it—from watch and wait to the Chinese menu of treatments, which are becoming available. For targeted discussions about COVID and its impact on cancer patients, please tune into Andrew Schorr’s biweekly webinars on COVID and cancer, and you can get all the information about them at patientpower.info.

We want to thank AbbVie, Genentech and Adaptive Biotechnology for generously sponsoring today's program. None of the companies has editorial control. The program is produced by Patient Power.

We want to welcome Dr. Barrientos. Could you please first off share where you are, your title and what you're working on in the CLL world?

Dr. Barrientos:

Thank you, Carol. My name is Jacqueline Barrientos, and I work at the CLL Research and Treatment Program in Long Island in New York. I work with Dr. Kanti Rai who developed the Rai Staging Criteria about 50 years ago, and also with Dr. Nicholas Chiorazzi who discovered and worked on the role of the heavy chain immunoglobulin. Those are my mentors, and essentially our group sees mainly CLL patients. We've been involved with all the clinical trials involving all the novel targeted agents such as ibrutinib (Imbruvica), acalabrutinib (Calquence), idelalisib (Zydelig), venetoclax (Venclexta), you name it. We all have experience with that, and we participate in comparative trials. We are here to help you and to share our knowledge.

Carol Preston:

You've mentioned a number of the treatments now available to patients, and it seems that based on your research, that combination treatments are more effective regimen than just single agents. Is that correct?

Dr. Barrientos:

At the beginning, when we were doing the relapsed refractory disease, of course you start with just one type of agent and we found excellent results. The only problem is that the majority of them, when taking forever—continuously, I think this is progression may cause some undue toxicities. Our goal has always been to combine to the point where you can achieve a deeper response. With that, allow for the patient to have a therapy-free holiday where they are in remission without taking any therapy.

Carol Preston:

Excellent. Well, we have many, many questions, so let's get to them. Michael has a question about FISH and flow cytometry. You'll forgive me, I will put on my reading glasses, so I can actually read the questions. Michael wants to know, “Will the results of FISH and flow cytometry tests vary significantly over a period of years? And will positive and negative deletions change after treatment?”

Dr. Barrientos:

Yes, it does indeed change and it affects their therapy choice. It's very important to always have your FISH at the time before starting any therapy, because there are a couple of chromosomal aberrations that may lead to a more aggressive disease, and that also will not respond to chemotherapy. For example, deletion 17p. That's one of the chromosomal aberrations that we know that don't respond to chemotherapy. As such, you should not receive bendamustine (Bendeka) or fludarabine (Fludara) based regimen. Now, we also recommend to test a mutation called TP53 mutation and that's by DNA sequencing because that may be missed with a FISH analysis.           

Now, when you were first diagnosed, chances are less than 10 percent of the patients will have this deletion 17p mutation. But as patients get therapies, the therapies themselves may allow for clonal selection of a more aggressive form of the disease. As such, patients that did not have a 17p deletion may, at the time of relapse, have a different markup or chromosomal presentation. The cells and the disease change. The second time or the third time you receive therapy, you might actually have a chromosome 17p deletion, which may need to be treated differently. Up to 30 to 50 percent of the patients can have that aberration.

Carol Preston:

It's very interesting you mentioned 17p because when I relapsed in 2010, 17p was there. However, because I saw a CLL specialist, I learned that only 4 percent of my cells were involved in that, and I actually was a candidate for FCR. That was in 2010 and here we are 2020. Knock on wood, but that, what I'm really advocating is to see a CLL specialist to really get very granular with your diagnosis. Now, Jane asks about drug decisions. She's 74. She's never been treated, and she has good genetic markers. She's trying to decide between a number of therapies, which would be BR, bendamustine-rituximab (Rituxan), venetoclax and other new drugs. Any thoughts and suggestions?

Dr. Barrientos:

Everything is based on your co-morbidities and your risk assessment of the patient. There's that art of medicine, because there's no real head-to-head comparison between drugs such as—regimen such as BR against venetoclax with obinutuzumab (Gazyva), for example. We just know from the trial that was presented by Jennifer Woyach at ASH, at the Annual Society of Hematology, that bendamustine and rituximab was compared against ibrutinib-based therapies, against ibrutinib monotherapy or ibrutinib in combination with rituximab, and the response rate was similar, but the time in remission was much longer in patients treated with ibrutinib. However, there was no survival advantage, and that's the reason why in other countries, such as for example, Canada, they still use BR as a frontline regimen. Now in America, we have moved away from regimens that contain chemotherapy for many reasons.      

A good guess that part of it is the toxicity profile. You have more myelosuppression, which means you may require blood transfusions, platelet transfusions. There's a higher risk for infection with chemo-immunotherapy approaches. That's the reason why ibrutinib may be an option. But there's never been a head-to-head comparison of ibrutinib against venetoclax with obinutuzumab in frontline treated patients. It's a very personal choice. Some people prefer ibrutinib because of the ease of just starting a pill without having to monitor closely for tumor lysis syndrome, which is a known side effect of venetoclax, but the beauty of venetoclax is that it's a fixed regimen. You can take it only for 12 months in combination with obinutuzumab, and chances are that 80 percent of the patients will be still in remission two years or three years later. That's amazing, right? Compared to ibrutinib that you have to take forever, there's no one-size-fits-all at this moment. Patients should discuss with their providers what therapeutic options there are for them available, and then make a decision based on the risk-and-benefit profile.

Carol Preston:

Just what I was going to say, that we don't want anyone to walk away substituting what you hear on this program for the consultation with your medical providers. Moving on to IgHV-mutated status from Nancy, this is a rather granular question, “I carry the 321 gene family, and my IgHV-mutated status is mutated. I've been told that that gene family actually makes me unmutated.” Some clarification, please.

Dr. Barrientos:

Yes. The 321 family usually appears in patients that carry the unmutated form of the disease. Now, having said that, there is some minority of patients with mutated state that actually carry that same family, 321. It's about 2 to 3 percent of the patients. What this means is that the patients are at a higher risk of progression of disease. But having said that, it's just statistics. You are your own. I have met patients that carry a 17p deletion, and they don't behave more aggressively. They behave like a very indolent form. We've all seen those patients. There was actually a paper written by a group from Mayo and MD Anderson Cancer Center in Texas.         

Everyone is different. Yes, statistically speaking, that particular presentation of the disease may be correlated with a more aggressive form of the disease, but it doesn't mean that it will happen to you or that because of that, you will behave on some mutated disease and that you choose your therapeutic strategy when you need therapy. There's a chance you may never need therapy. Some people with mutated disease are lucky that they will never need therapy in their lifetime, but they still have the other side effects of CLL, which includes higher risk for infections or higher risk for secondary malignancies.

Carol Preston:

Okay. Very good. A question about a drug that I was on, or a couple of times, rituximab from Loretta, how long does it stay in your system after you stop treatment?

Dr. Barrientos:

The half-life of the drug is about one week. However, there is the possibility of the persistence of the monoclonal antibody that the median duration of the persistence is about three months. Having said that, there have been reports of some of the toxicities from the drugs such as neutropenia or curing up to a year after stopping the drug. They have life per se, meaning the amount of time that the drug is in your system may be out by one week or two weeks, but the effects of the drug are still in you, lasting at least three months on average.

Carol Preston:

One of my favorite questions has to do with fatigue coming from Jeff. He's newly diagnosed. He's stage 0, great markers, mutated, but he's exhausted. What does he do?

Dr. Barrientos:

Fatigue is one of these difficult symptoms that we don't really have a very good answer at this time. The first thing you need to do is make sure that you don't have anemia, which is the most common form of fatigue. Now, if you have ruled out any form of anemia, then you have to rule out other conditions such as thyroid disorder, chronic infections like hepatitis that may cause that or Lyme disease or some other infectious disease that could be contributing to this fatigue. If all of those symptoms or infection, risks, or other form of conditions having ruled out, then it's attributable to the CLL. Then, that may be a reason to start therapy even though we try to avoid starting therapy just for fatigue.

Carol Preston:

Let me just jump in and ask if you've ruled out all of those ancillary conditions, is there anything you can do with diet and/or exercise?

Dr. Barrientos:

We always recommend doing exercise, because it becomes a vicious cycle that you are tired, so you stop exercising in that parameter. Then, you start becoming more and more sedentary, and that can increase your fatigue component. We always try. Even if you, for example, have issues with your back and you cannot run or with your knees, then you can always do other types of exercise that is not so hard on your joints, such as joining a swimming pool where you can do swimming or some other form of non-high impact exercise. But definitely, we recommend at least three times a week exercise and also good diet, stay away from processed food, healthy varied diet with vegetables, protein. It can be meat sources, or some things that we recommend for our CLL patients are green tea and vitamin D. Those are things that we just also recommend.

Carol Preston:

I think you've touched upon fixed duration versus taking indefinitely. But Robert wants to know if venetoclax, is that basically fixed duration? If a patient goes on venetoclax, can he or she get off of it at some point?

Dr. Barrientos:

The original approval for venetoclax was four 17p deletion patients. That was for indefinite therapy. Then, because patients with 17p will relapse sooner, and so they didn't need to stop. But with venetoclax, it's a drug that you can actually achieve minimal residual disease (MRD) that is undetectable, meaning you can look into the bone marrow and not see any CLL cells in one in 10,000 cells. What we noticed when we started doing the Phase I trial was that many of our patients were able to achieve that undetectable MRD state. We approached the company and as investigators, we said, "What happens if we stop?" We did an analysis of those patients that stopped therapy, and they were still in remission for a prolonged period of time, similar to what you would expect with chemo-immunotherapy approaches.    

That's why the clinical trials started with a defined duration of therapy. The original trial for relapsed refractory disease was for two years in combination with rituximab, and it worked so well that that was moved into frontline therapy in combination with obinutuzumab and that also is showing that you can just give the therapy for one year and then be in remission for several years later. We think that the people that are going to relapse, it's not because they stop responding to the drug, because you stop the drug. It's actually progression because it had to be in their biology that they were going to progress, because some of the progressions are being seen right before you stop the 12-month mark or two-year mark.

Carol Preston:

Sure. Right. Well, moving on to headaches. Oh, my goodness. Walter is on Calquence, and he said one of the side effects for him were headaches. Now, he said coffee stops them. That would be the caffeine, but, “I'm up at midnight drinking coffee,” which probably is not advisable. I know that if I were drinking coffee at midnight, I'd be getting to sleep at 6:00 AM. Any thoughts about that?

Dr. Barrientos:

It is a common side effect for patients on acalabrutinib. We still don't understand why it happens, but it happens more in America, believe it or not, than in our counterparts in Europe. We think that it might be because the caffeine content of the coffee is stronger with those espressos, but you can also take acetaminophen (Tylenol) if you don't feel like drinking coffee in the middle of the night. Overall, usually the headaches get away or stop around four months into therapy. It's just a matter of just holding it a little bit longer, and then it will disappear.

Carol Preston:

Okay. Just staying on the subject of side effects, Sandy wants to know about skin rashes. She is watch and wait. Is there any connection between CLL and skin rashes?

Dr. Barrientos:

Absolutely. We always tell our patients, especially during the summer months to put on a lot of bug spray because for some reason, if you get a bug bite on your skin, it will be much more inflamed than anyone else that doesn't have the condition of CLL. It's like an inflammatory response. The skin rashes can happen before you get therapy and also due to therapy, there are some reports of skin rashes on ibrutinib and acalabrutinib. It's a known potential issue with patients with CLL. We just say, in order to protect yourself from bug bites, which are known triggers for these skin rashes, just wear long sleeves. When you will go outside, put on bug spray and wear a hat so that they don't bite you in the face.

Carol Preston:

All right. Good advice for almost any circumstances.

Dr. Barrientos:

Yeah.

Carol Preston:

We have a final question from Kim about CLL and age. She wants to know, “Does age impact outcome? Is the outlook better for younger patients?”

Dr. Barrientos:

Okay. It is a difficult question, because it's a disease that usually happens and is diagnosed in their 70s. That's the average for patients diagnosed with CLL. Because of that, by the time that you are in your 70s, you have more co-morbidities, which include high blood pressure or cardiac arrhythmias or diabetes, or some other co-morbidities that may impact your ability to tolerate a drug regimen. Just to explain how you respond to a drug, we had two inter group studies, major, national and white where ibrutinib was given to patients older than 65 or to patients younger than 70, two groups.         

The same patients were followed-up to see what side effect toxicity profile they would have. Patients treated with ibrutinib that were in the young cohort, very few of them had an atrial fibrillation event or hypertension, whereas patients that were in the older cohort, they had many events of cardiac arrhythmias or hypertension. It's intrinsic just because you're older that that's not allow you to tolerate a regimen as good as when you're younger. Age, we put you at a higher risk category because of that because of your inability to tolerate. When you stop taking a drug that is working, then the disease comes back sooner.

Carol Preston:

Yeah. I'm 70 and well aware of the pitfalls of getting older and accumulating.

Dr. Barrientos:

You don't look a day over 60.

Carol Preston:

Thank you. Oh, thank you so much, Dr. Jacqueline Barrientos for sharing your CLL expertise and insights. We'll be doing many more of these programs, so please keep your questions coming. I do want to thank again, AbbVie, Genentech and Adaptive Biotechnology for their support to Patient Power and to all of you who raise such important CLL issues. I'm Carol Preston, and your questions help unlock better treatments and outcomes.

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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