Let’s Talk CLL
Patients & Doctors Discuss the Latest Live – Video Transcript
Edited by: Katrina Villareal
Discover the forefront of chronic lymphocytic leukemia (CLL) research and care in our Let’s Talk CLL live discussion held at MD Anderson Cancer Center on October 14, 2023. To watch the video conversation, click here.
Join us as a panel of CLL experts, featuring Dr. William Wierda, MD, Ph.D., from MD Anderson, Dr. Nicole Lamanna, MD from Columbia University Medical Center, Dr. Adam Kittai, MD from the Ohio State University, and Jackie Broadway-Duren, PhD, DNP, APRN, FNP-BC from MD Anderson, converge to delve into the most recent developments in CLL research, clinical trials, treatment approaches, and holistic care strategies.
With patient advocate moderator Jeff Folloder, The Patient Story strives to bridge the gap between medical expertise and the lived experiences of patients. This inclusive discussion fosters a truly comprehensive dialogue that empowers, informs, and inspires hope. Join us on this enlightening journey into the world of CLL, where science meets the human experience.
Thank you to AbbVie & BeiGene for their support of our patient education program! The Patient Story retains full editorial control over all content. This interview has been edited for clarity and length. This is not medical advice. Please consult with your healthcare provider for treatment decisions.
- Current CLL Treatment Options
- Watch & Wait
- Vaccines and CLL
- Optimized Care & Limiting Side Effects
- Finding a CLL Specialist
- Strategies for Coping & Living Well with CLL
- Final Takeaways
It’s possible to live a great life even with a CLL diagnosis.Jeff Folloder
Jeff Folloder, CLL Patient Advocate
Jeff Folloder: Many of us are on some portion of a journey with chronic lymphocytic leukemia.
My name is Jeff Folloder. I’m a passionate, patient advocate. I do this often and passionately because I want everyone to know that it is not just possible to live a good life with CLL, it’s possible to live a great life with CLL.
A little over 13 years ago, my first doctor diagnosed me with CLL and in a very brusque way informed me that I have six years to live. Sounds fun, right? I fired him.
I wound up at MD Anderson and my doctor at the time, Dr. Michael Keating, picked me up out of the chair, gave me a big giant hug, and said, “You’re going to die with this not from this,” and that felt good.
I had the honor to speak at his retirement gala and he pulled me off to the side and said, “I’m changing my mind. We’re going to cure you.” That had a lot of gravity.
Why do I think that it’s possible to live a great life even with a CLL diagnosis? I’m doing everything that I want to do with my life and not at a low level — at a really loud volume level. I’m a better father, a better husband, and a better friend. I’m doing everything that people who don’t even have a cancer diagnosis could dream about doing.
I’m training to do the Bataan Death March Memorial Marathon in March 2024, which is held in the high desert of New Mexico. I’ll be over a mile up doing 26.2 miles off-road. I pound out the miles every morning. I love doing it. Do I have the typical CLL patient fatigue? You bet, except mine’s self-inflicted.
My doctor right now is Dr. Wierda. Every time I see him, he asks me why I worry so much. I shouldn’t worry, but I do.
I want to thank our sponsors, AbbVie and BeiGene. This program is not medical advice. You’re here to learn. Anything specific about your condition and your treatment should be discussed with your doctor.
Joining us on our panel are Dr. William Wierda from MD Anderson Cancer Center, Dr. Nicole Lamanna from Columbia University Medical Center, Dr. Adam Kittai from The Ohio State University Comprehensive Cancer Center, and Dr. Jackie Broadway-Duren from MD Anderson Cancer Center.
Dr. William Wierda
Dr. William Wierda: My background is in immunology. I have a Ph.D. in immunology and I’ve always been interested in immunology.
CLL is a unique disease from an immunologic perspective. As a fellow, I was working with Tom Kipps at the University of California San Diego and trained with him. I was doing immune-based treatment strategies and that was the beginning of my interest in CLL and why I have stuck with CLL for many years. Then Michael Keating recruited me to Anderson. He is somebody who’s inspired me for many, many years with my work in CLL.
Dr. Nicole Lamanna
Dr. Nicole Lamanna: Michael’s also been a mentor of mine for years, too. I enjoyed taking care of the whole patient so I was inspired by leukemia mentors at Memorial Sloan Kettering when I was an intern and a resident. Because of that aspect of handling the entire patient, acute leukemia and leukemia, in general, became a passion of mine.
I wound up doing my fellowship and staying in leukemia ever since. Chronic lymphocytic leukemia affects not just the blood but your whole body and many different organ systems and your immune dysfunction. I like handling the whole patient and that’s why I’ve stayed in CLL.
Dr. Adam Kittai
Dr. Adam Kittai: I enjoy seeing my patients longitudinally over time. With CLL, it’s a disease our patients live with for a long time. It’s a pleasure for me to get to know my patients, get to know about their families, and see them throughout their lifetime.
Dr. Jackie Broadway-Duren: When I first came to MD Anderson, I worked with acute leukemias and it became so emotionally overwhelming. Dr. Keating seized the opportunity and recruited me to work with his CLL team.
CLL patients are very unique. You get to follow them for a long time. You get to know their families and you become a part of their families. Most importantly, this is the leukemia that has some of the most exciting treatments currently available and on the horizon so that’s why I stayed with CLL.
Current CLL Treatment Options
Jeff: Dr. Wierda, when I first started, there was one choice. What has happened?
Dr. Wierda: In the last 10 to 15 years, the evolution of targeted therapy for patients with CLL has changed the natural history of the disease and impacted survival. We’ve developed oral agents that are extremely effective at controlling the disease, like the BTK inhibitors and venetoclax, a BCL2 inhibitor.
We’re working on optimizing how to use those and how to work with them to develop curative therapy. The landscape has changed remarkably over the last 10 to 15 years. We’re not giving chemotherapy anymore, which used to be the standard treatment. We have highly effective treatments that are very well tolerated.
In the last 10 to 15 years, the evolution of targeted therapy for patients with CLL has changed the natural history of the disease and impacted survival.Dr. William Wierda
Jeff: That sounds great. But, Dr. Lamanna, have we left chemo on purpose?
Dr. Lamanna: Regimens like fludarabine, cyclophosphamide, and rituximab or FCR, which Dr. Keating championed, were very effective regimens. It’s just that they had a whole host of side effects and were less targeted.
There are patients in different parts of the world who still get these therapies because they may not have access to these newer agents. We have more focused, better therapies that have fewer side effects and deal with the biology more precisely so we’ve moved away from chemoimmunotherapy.
Jeff: Dr. Kittai, can you tell us about these targeted therapies? What are they doing and why are they so important to patients today?
Dr. Kittai: Ibrutinib, acalabrutinib, and zanubrutinib are Bruton’s tyrosine kinase (BTK) inhibitors.
Bruton’s tyrosine kinase is an essential messaging protein that allows the CLL cells to survive. These three drugs target Bruton’s tyrosine kinase and prevent it from working. It’s an essential pathway within the B cell receptor that activates the CLL cells. The BTK inhibitors inhibit that specific protein to prevent the CLL cells from dividing and living a long time.
Currently, the only approved BCL2 inhibitor is venetoclax or VENCLEXTA. Cancer cells like to increase signals that allow them to live longer and avoid dying. Our mitochondria are the powerhouse of the cell. Two balances live on top of it. There’s the I’m-going-to-die balance and the I’m-going-to-live balance.
Cancer cells like to increase the I’m-going-to-live balance. Venetoclax corrects that and increases the I’m-going-to-die balance. It leads to an equilibrium improvement for our CLL cells, allowing for the drug to work and treat the CLL.
We’re not using PI3K inhibitors, like ZYDELIG (idelalisib), as much as we used to. They also impact the B-cell receptor pathway, which is another way that the cells divide. PI3K inhibitors work very similarly to BTK inhibitors, but a different molecule altogether.
Jeff: Dr. Broadway, you’ve been watching patients go through this evolution. They started with very narrow choices. We revolutionized things with FCR and similar treatments and now we’re moving on to targeted therapies. How are patients responding to this new mode?
Dr. Broadway-Duren: Patients are loving the oral therapies. Many of them reported feeling like they can play golf for the first time in years because they have the flexibility now. These medications are taken at home so it frees them up to do more activities. No one wants to sit in a chair for hours for chemotherapy nor do they want to deal with the side effects of chemotherapy.
I clearly remember when ibrutinib was about to be approved and we were anxiously awaiting the approval of ibrutinib. We had phone calls months ahead of time. People wanted to be on the first studies that we had for ibrutinib. It has revolutionized the care for CLL.
These drugs are not without side effects, but they are tolerable and we can work through them with the patient. It takes a multidisciplinary approach, but this is certainly a better option for patients than chemotherapy.
Jeff: I’m in watch and wait again. I started over 13 years ago.
I went through a clinical trial at MD Anderson where I used a single-agent immunotherapy drug. Although that drug is no longer front line, other immunotherapy drugs are still being paired with some of these new treatments.
Dr. Wierda: The ALPINE and ELEVATE trials are randomized phase 3 clinical trials. Those look at one BTK inhibitor versus another. Both trials compare a second-generation BTK inhibitor against ibrutinib, which is the first-generation BTK inhibitor.
Those trials demonstrated an improvement in tolerability with the second-generation BTK inhibitors over what has been the standard long-term, which is ibrutinib. There are more cardiac toxicities with ibrutinib compared to the second generation.
Those trials compared two treatments and showed that the tolerability and toxicity are a bit less with the second-generation inhibitors compared to ibrutinib. There’s some suggestion that zanubrutinib on the ALPINE trial may have a better progression-free survival.
The ALPINE and ELEVATE trials demonstrated an improvement in tolerability with the second-generation BTK inhibitors over what has been the standard long-term, which is ibrutinib.Dr. William Wierda
The follow-up is different in both trials. The patient population is different. They demonstrate that the second generation is preferred over the first generation. I don’t think you can make any conclusions between the different second-generation BTK inhibitors, acalabrutinib versus zanubrutinib.
Other phase 3 randomized trials compare different treatments, like iLLUMINATE. Those trials look at chemoimmunotherapy, which has been the long-term standard, versus targeted therapy. They’re predominantly BTK inhibitor-based treatments using first-generation and second-generation BTK inhibitors.
A number of those trials have clearly shown improvement in progression-free survival with oral BTK inhibitors over chemoimmunotherapy. A couple of trials have shown survival advantages if you start with a targeted therapy.
BTK Inhibitors + Venetoclax
Jeff: Dr. Lamanna, one of the things that’s been combined is ibrutinib with venetoclax. Does it work well? Why is it approved in Europe and not the US?
Dr. Lamanna: Yes. As Bill alluded to, there are lots of studies that have shown the benefit of these agents over chemoimmunotherapy. We’re trying to look at different combinations to see if we can tweak these therapies better. There are oral-oral combinations of BTK inhibitors plus venetoclax.
Many trials are looking at ibrutinib and venetoclax, acalabrutinib and venetoclax, or zanubrutinib and venetoclax. There was a study in Europe called the GLOW study that looked at ibrutinib and venetoclax versus more traditional chemoimmunotherapy with chlorambucil and obinutuzumab. Chlorambucil and obinutuzumab are not used as much in the US anymore, but it was a gold standard for older frailer patients with CLL as a standard chemoimmunotherapy regimen.
Nobody was doubting that the ibrutinib-venetoclax arm would be better. There were some toxicities from this regimen. Based on the combination of ibrutinib and venetoclax from this GLOW phase 3 randomized study, this was approved as a regimen in Europe.
Even though ibrutinib is a great drug and it’s done well for our patients, the newer generations have fewer side effects.Dr. Nicole Lamanna
There are different regulatory boards here versus in Europe. Our regulatory boards want us to look at some of the newer generations, acalabrutinib or zanubrutinib, with the oral-oral combinations and some of our phase 3 studies before this oral-oral combination gets approved. Ibrutinib and venetoclax are not approved in the US yet.
Because of those head-to-head studies of ibrutinib versus acalabrutinib or ibrutinib versus zanubrutinib, we’ve seen that the newer generations of these BTK inhibitors have fewer cardiac toxicities.
Even though ibrutinib is a great drug and it’s done well for our patients, the newer generations have fewer side effects. Because of that, partnering with a newer agent that may have less toxicity is probably where the FDA will want to go versus ibrutinib.
Time-limited Therapy vs. Continuous Therapy
Jeff: We started with treatment programs that were broad brushes. With these trials, we’re narrowing the focus so that instead of treating all CLL patients with one regimen, we’re paying attention to what kind of CLL we’re talking about and what would be the best personalized care. Is that a fair statement?
Dr. Kittai: That’s a fair statement. We don’t know if BTK inhibitors are better than venetoclax plus obinutuzumab. There hasn’t been a randomized phase 3 trial to tell us that this approach with time-limited therapy is better than continuous therapy.
If we don’t know which way is better, it comes down to a lot of different factors that are patient-focused, like comorbidities and the risk of CLL.
One of the biggest things that helps me decide what to give my patient is my patient. When we’re talking about time-limited therapy versus continuous therapy, a lot of our patients have a specific want of either of those options. Ultimately, it comes down to a conversation of the pluses and minuses of each regimen, which certainly is patient-specific and patient-focused.
There hasn’t been a randomized phase 3 trial to tell us that this approach with time-limited therapy is better than continuous therapy.Dr. Adam Kittai
For instance, continuous therapies are generally very well tolerated. After I start a BTK inhibitor, I see my patients two weeks later to make sure everything’s okay, one month after that, and then every three months after that so it’s an easy start-up.
Whereas with the venetoclax plus obinutuzumab time-limited therapy, the patient has to come into the clinic weekly for the first two months. We have to do a little bit more monitoring because the cell counts can get a little low, but everybody gets a stop after a year.
If you have someone younger, who has an active lifestyle, and who can’t get off work to come into the clinic once a week, they may opt for continuous therapy. A similar person who can’t see themselves taking a pill for so long may opt for time-limited therapy because they want to get it done with.
Each patient is different. Now, we have a lot of different options to use.
Jeff: Let’s talk about some of these clinical trials, which are giving us even more options. We’ve got the CLL17 trial, the ALLIANCE trial, and pirtobrutinib there. There are a couple of trials going on there.
I noticed we’re not talking about pairing. We’re talking about triplets as well. Tell us what’s going on and why patients need to be aware.
Dr. Kittai: BTK inhibitors haven’t been compared to time-limited therapy to tell us what to pick and which is better so that’s why all of us are excited about the CLL17 trial. This is a randomized phase 3 trial that’s comparing continuous ibrutinib versus time-limited venetoclax plus obinutuzumab versus time-limited ibrutinib plus venetoclax.
Hopefully, we’ll have a better understanding of which way to go for our patients in terms of what might be the most efficacious and safest option because we don’t know how this trial is going to pan out.
As Dr. Lamanna alluded to, when we thought of the GLOW trial, we were pretty sure that ibrutinib plus venetoclax would beat chlorambucil plus obinutuzumab. With the CLL17 study, I honestly don’t know. We’re excited to see how that trial goes. Unfortunately, it’s going to be some years before we find out.
We don’t design trials with a new treatment that we don’t expect to be better. We always think that they’re going to work.Dr. Adam Kittai
The ALLIANCE trial is ibrutinib plus obinutuzumab versus ibrutinib plus obinutuzumab plus venetoclax. Similarly, a lot of us thought that the ibrutinib-venetoclax-obinutuzumab combination was going to be more toxic than the ibrutinib plus obinutuzumab because, in general, when you add more drugs to a regimen, the toxicity generally increases.
But with a time-limited therapy, the toxicity outweighs the efficacy benefit that you might get from the triplet combination. At ASCO, my mentor Dr. Woyach presented the study because it had to end early. More patients died on the triplet arm, which we were all surprised about.
Ultimately, we had to see how this plays out long term. COVID was a true impact here. Unfortunately, more patients passed away from COVID on the triplet arm. If you take out those COVID deaths, it does look very similar so we’ll see how this plays out long term.
We don’t design trials with a new treatment that we don’t expect to be better. We always think that they’re going to work. Ultimately, what this tells us is that we have to roll our patients onto clinical trials so we can get better answers to the questions that we have.
When we enroll patients in clinical trials, we can follow them forward in time to get the data that we need so we can share the results with the community at large.
We think about the different aspects of your disease, yourself, and other medical problems when we talk about your options for therapy.Dr. Nicole Lamanna
Jeff: How does one choose between time-limited and continuous therapy?
Dr. Lamanna: As Dr. Adam suggested, this can be a lengthy discussion. We look at disease characteristics, but we’re looking at other factors, too. We’ll take into consideration your comorbidities.
Different drugs have different side effect profiles. BTK inhibitors and venetoclax are two oral agents that are both very effective, but, as said before, we don’t know that one is necessarily better than another.
We take into consideration patient considerations. Do you want to do something that’s time-limited and more intense initially? Can you afford to do that and be ever present, particularly in the beginning when there are more side effects?
Part of it is the circumstances of the patient but also the side effects of the drug and what medical problems you may have, what other medications you may be on for these other medical problems, whether or not there are drug interactions, and how do we overcome some of those issues, depending upon the drug.
It winds up being a very long conversation when we think about the different aspects of your disease, yourself, and other medical problems when we talk about your options for therapy. The good news is now there are a lot of different options, which weren’t available before.
CAR T-cell Therapy
Jeff: Dr. Broadway, one of the things that was very exciting and talked about in the CLL community was CAR T-cell therapy. Frankly, from my perspective, it was intimidating. It sounded pretty dramatic. What goes on with CAR T?
Dr. Broadway-Duren: In our immune system, we have B cells and T cells. B cells generally help provide immunity. T cells naturally release cytokines that can kill off things that shouldn’t be there.
With CAR T-cell therapy, the principle is that they would extract your cells, send them to a lab, and incubate them with CAR T cells, which have a natural killer instinct so that the T cells then recognize CLL cells and learn to fight against them. They expand these cells in a laboratory setting so that they can get enough of them and give them back to you as they would with a stem cell transplant.
Jeff: Dr. Wierda, this sounds great. Why aren’t we doing this for everybody?
Dr. Wierda: Not everybody can tolerate it very well. There are toxicities associated with CAR T-cell therapy. I’ve been working in the CAR T cell area for many years and we have seen data that dates back many years ago. Carl June and his group treated patients with CAR T cells many years ago.
Many patients have been cured by CAR T-cell therapy. Not all of them are cured. The side effect and toxicity profile is difficult for some patients. When patients get sick, they require hospitalization. Some patients end up going to the intensive care unit.
The CAR T work began with CLL years ago and that product has leapfrogged for patients with acute myeloid leukemia and for DLBCL. That scenario illustrates some of the challenges. It’s not as effective in patients with CLL and some side effects and toxicities are a bit higher in patients with CLL compared to other diseases.
While the story started with CLL, we’re still catching up. I think we will have a product that’s approved. We worked on the TRANSCEND study and I anticipate that there are patients who have been in remission who have probably been cured of their disease. But logistically and from a toxicity perspective, it’s a little bit harder to work in patients with CLL.
Very successful in other diseases so I think that it will move along in CLL and get approval.Dr. Nicole Lamanna on CAR T-cell therapy
Jeff: That sounds reasonable and prudent. I would guess that you’re hedging a little bit. Maybe those toxicities are probably a little bit intense.
Dr. Lamanna: We started working on CAR T cells when I was at Memorial. It was one of the first studies and so this is going back over a decade ago. The reason, in part, why it’s been slower in CLL is because, in those other cancers where it is approved, they had fewer therapy options.
We’ve had all these wonderful targeted therapies that have become available. Whether it’s fortunate or not fortunate, CAR T-cell therapy got relegated to multiple relapsed patients.
We have a lot more experience using CAR T because it’s been around now for over 10 years. We’ve improved on some of the side effects. In some of the early CAR T-cell clinical trials, some patients passed away from the therapy. We’re learning how to mitigate some of the toxicity.
There have been some very good results from studies, such as the TRANSCEND study. I think we will get approval. I think it’ll be in the relapsed setting. It may move up as we use it in combinations for certain individuals. It has some activity in some of our refractory patients, patients with Richter’s syndrome, for example, and patients whose CLL has transformed into a more aggressive lymphoma.
There are important uses for CAR T cell. It’s a different type of modality using your immune system to attack your CLL cells. Very successful in other diseases so I think that it will move along in CLL and get approval. It’s just that we also have the benefit of having so many other agents. We’ll see ultimately where it fits in the grand scheme of things. Right now, in the relapsed/refractory setting is an important option.
Dr. Kittai: We have three types of clinical trials. We have phase 1 trials, phase 2 trials, and phase 3 trials.
Phase 1 trials are first in human or dose finding. They’re usually very small, under 50 patients. They’re looking for a dose and safety of the drug.
Phase 2 is meant to find the initial efficacy and how well it works.
Phase 3 is usually how a drug gets approved. You’re comparing the new intervention versus something that we’re already doing. The patient is randomized to two arms and the ultimate goal is to find out whether or not the new drug works better than the standard of care.
TRANSCEND study is a phase 2 study. It was a single-arm study that looked at patients who received BTK inhibitors and BCL2 inhibitors so that’s the ibrutinib-acalabrutinib-zanubrutinib or venetoclax.
Patients had been treated with our main lines of therapy and so it looked like if you responded to the CAR T-cell therapy, you did well.Dr. Adam Kittai
You get CAR T-cell therapy one time. You get the blood taken out of you, it gets sent to the manufacturer, and the CAR T cells get infused back. Once the product is available, you get chemoimmunotherapy to make it easier for your cells not to reject the CAR T cells that you’re about to get.
We have to follow you pretty closely for 30 days. Liso-cel happens to be the safest of the three that are currently approved right now for non-Hodgkin’s lymphoma.
We’re looking for ways to mitigate the toxicity associated with CAR T-cell therapy. The interesting way that we’re doing that is with BTK inhibitors concurrently with the lysis cell, giving steroids before giving various other agents to try to mitigate the toxicity.
For the TRANSCEND study, which accrued about 100 patients, of the patients who got the product, only about 80 got undetectable minimal residual disease responses so that means that they weren’t able to detect the CLL in these patients.
These patients had been treated with our main lines of therapy and so it looked like if you responded to the CAR T-cell therapy, you did well. Unfortunately, there were some nonresponders and that’s classic with CAR T-cell therapy. If you respond, you do well and if you don’t respond, you don’t do so well, which makes sense, too.
In general, this was a high-risk group of patients who received all of our primary lines of therapy with this one-time therapy and there was a response rate of 60%. Hopefully, based on this phase 2 study, it gets accelerated approval, which means that you only have approval for a few years. The phase 3 studies will come down the line hopefully.
Obinutuzumab + Venetoclax
Jeff: Dr. Jackie, what do patients find most challenging in tolerating the OV treatment side effects?
Dr. Broadway-Duren: One of the things that they find challenging is the immediate effects. After getting an obinutuzumab infusion, they may have reactions within the first 72 hours. They may run a fever. We educate the patients well so that they’re not surprised that they may experience some fever, chills, or changes in blood pressure during the infusion.
With venetoclax, the most reported side effect I’ve heard is diarrhea and that’s something we work through with the patient. As a provider, we look at the toxicity of neutropenia. This doesn’t happen in everyone, but there is some degree of neutropenia.
Venetoclax is a once-a-day dosing. Sometimes they find it challenging to get all four tablets in when they reach the full dose capacity for the drug.
The greatest is GI side effects, primarily loose stools. We prepare the patients by telling them ahead of time. There are medications, such as IMODIUM A-D, that they can buy over the counter or a prescription strength anti-diarrheal medicine they may need.
Jeff: Dr. Bill, we’ve talked about the mabs and the ibs. Bispecifics is a new variant I have to learn.
Dr. Wierda: Bispecifics are antibodies, which we have used for years in CLL; rituximab being the first one. We have obinutuzumab, which has been mentioned.
Monoclonal antibodies bind to certain proteins. They identified proteins on CLL cells that they could target. CD20 is the target for rituximab and obinutuzumab. Campath (alemtuzumab), which is a drug used years ago that we don’t use anymore, targets CD52.
Bispecifics are engineered molecules that target some of those proteins and are linked to an antibody that targets a protein on your T cells called CD3. The bispecific binds CD20 on the CLL cells and CD3 on the T cells of your immune system. When those two cells come together, the molecule will trigger the T cell to attack the CLL cell and kill the CLL cell.
These drugs are approved now for non-Hodgkin’s lymphoma, but we don’t have any approved for CLL yet. There are several clinical trials right now that are studying bispecifics.
Epcoritamab is one of the bispecifics that’s already approved but not for CLL. It’s under investigation for patients with relapsed CLL and Richter’s transformation. This is a category of medications I’m very optimistic about. We have heard preliminary data demonstrating activity in treating CLL with these compounds.
There’s a little bit more work we need to do in this area in terms of optimizing the efficacy and making it a better, well-tolerated treatment for our patients, just like CAR T cells.
Dr. Lamanna: Bispecific antibodies have more similar side effects to CAR T because of the link to the CD3 or the T-cell activation so we need to work on that.
Jeff: This is exciting. Dr. Wierda, we had a conversation about a year ago in the clinic where you gave me a new perspective. You told me that the goal of the staff and the team at MD Anderson was to keep me alive. The longer you kept me alive, the better the drugs would be when I needed them.
That was an Aha! moment for me because the first drugs that I had to choose from weren’t great. I wasn’t a big fan of the toxic profile and the side effects. I joined one of your clinical trials and got great results, and we weren’t even using that drug for CLL anymore.
There are always things on the horizon. I recommend patients look for clinical trials.Dr. Adam Kittai
Treatment for Relapsed/Refractory CLL Patients
Jeff: Dr. Adam, some patients aren’t able to tolerate some of these treatments. What happens when we’ve tried different treatments and the outcome is not looking great; what’s next on the horizon?
Dr. Kittai: For standard CLL, the area of unmet need is patients who have received BTK inhibitors and BCL2 inhibitors, and have progressive disease after that, or if they’re not able to tolerate either of those two medications.
CAR T-cell therapy is on the horizon. There are also new BTK inhibitors and new BCL2 inhibitors coming out as well.
As Dr. Bill said, we are having an explosion of options for our CLL patients and we do expect a lot of these drugs to get approved. One that is as close to approval as you can get is pirtobrutinib and I expect it to be approved as an accelerated approval any day now.
Pirtobrutinib is a BTK inhibitor — like ibrutinib, acalabrutinib, zanubrutinib — that was designed specifically to bind a little bit differently to the BTK protein, allowing it to work when the ibrutinib, acalabrutinib, and zanubrutinib stop working.
The first second-generation BTK inhibitors are what we call covalent BTK inhibitors (cBTKi). Pirtobrutinib is a non-covalent BTK inhibitor (ncBTKi). We’re starting to call pirtobrutinib our third generation. There are new BTK inhibitors, but the degraders are coming out. There are covalent/non-covalent BTK inhibitors so we’re now having fourth, fifth, and sixth-generation inhibitors.
Pirtobrutinib will likely be approved. It looks like a safe drug and is an option for patients who are refractory or cannot tolerate the two other medications.
There are always things on the horizon. I recommend patients look for clinical trials, but we will soon have two drugs approved for these patients specifically.
Jeff: Sounds promising and exciting.
Watch & Wait
Dealing with Fatigue
Jeff: Dr. Lamanna hates the term watch and wait. Patients, call it watch and worry. We’ve got cancer. We’re supposed to be doing something about this.
Dr. Jackie dealt with more watch and wait complaints. I remember coming in and you asking me, “How are we feeling today?” I would tell you I’m fatigued and you would make me go through the litany of what fatigue is. We had to figure out the difference between tired and fatigued.
We know that watch and worry is a heavy burden that we carry. No matter what all of you guys say, we’re still going to watch and worry. Is fatigue normal during watch and wait?
Dr. Broadway-Duren: Fatigue is normal with CLL in general. It’s normal to have a degree of fatigue as you’re watching and determining when it’s time to institute therapy.
When we’re trying to make a decision, I always try to reiterate to patients the optimal time to start treatment or if and when they need treatment.
It’s difficult. When a patient comes in, they may have a white blood cell count of 60,000. In their mind, they think that they need to get treated when, in fact, they have a good quality of life.
It’s normal to have a degree of fatigue as you’re watching and determining when it’s time to institute therapy.Dr. Jackie Broadway-Duren
There’s underlying fatigue so we try to get them to do things that may improve their fatigue, such as exercise. It’s important to find out other factors that may be contributing to fatigue. It may not always be CLL.
We’re monitoring everything very, very closely. There’s no set number in which we decide it’s time to treat a patient.
You’re going to have some degree of fatigue, but we try to work through it. When you have levels of fatigue where you need to go back to bed by 10 a.m. when you just got up at 8 and there are other things like night sweats, then maybe that’s the time to start looking at treatment options.
Jeff: One of the things that Dr. Jackie made sure I understood when I was reporting my fatigue was if I get refreshed from that sleep. Do I get refreshed from that nap? More importantly, is my fatigue impacting my ability to do the things that I want to do in life? Those are very important questions to ask yourself and they’re very important answers that you need to give to your medical providers. They need this insight into what’s going on with you so that they can help you make good decisions.
Our treatments are evolving. What’s available today is going to be different than what’s available in a year, and it’s going to be better in a year.Dr. William Wierda
Jeff: Dr. Bill, I’m in watch and wait for a second time. How long do I need to be there?
Dr. Wierda: Until you need to be. There have been several clinical trials done to determine whether or not there’s a survival benefit with early treatment.
Take 100 patients who are newly diagnosed and don’t otherwise need treatment. Half of them get early treatment while half of them don’t.
Those trials have not shown a benefit with early treatment versus watch and wait. That’s very important. We worry but it’s not to the detriment of your survival to wait and to move to treatment when you need treatment.
Our treatments are evolving. What’s available today is going to be different than what’s available in a year, and it’s going to be better in a year.
Treatment improves with time and you have to have some comfort and confidence in that. I’m a professional worrier. Let me worry for you. That’s my job. I’m serious about that.
Jeff: It’s not a joke. All my life, I have been a professional worrier. We have a little bit of agitation between the two of us because the week before my regular checkup at MD Anderson, I get wound up. I’ve been doing this for a long time. I know exactly what’s going to happen. I know exactly how the blood draws are going to work. I know exactly the rate at which the results are going to start pinging on my phone so I can get an idea of what’s going on.
Even though I know all of this, and I know it’s more than likely that the answer at the end of my clinic visit is, “See you in six months,” I worry. I get agitated. I obsess over it.
One of the things that I do is pound out more miles. You’re not supposed to do a half marathon before a blood draw and you’re not supposed to do it a second time. Pro tip: drink more water.
Some patients never need treatment for their CLL and it would be great if we could draw their blood and know exactly who they were because then they would never have to get any therapy or be exposed.Dr. Nicole Lamanna
Dr. Lamanna: This is truly a chronic illness, although everybody is trying to find curative therapy for CLL. We want you to enjoy your life.
I don’t like watch and wait. I do active observation and monitoring; that’s what I call it. We’re not trying to take away the worry and the concern.
Watch and win’s a great one because as you’re sitting on the sidelines, all these new therapies become available and it changes the standard of care.
Patients get the benefit of sitting on the sidelines as new therapies, guidelines, and changes are happening because of all the research that we’re doing. What might have been used five years ago may be very different from what’s used tomorrow. You gain the benefit of that without going through all the pain.
Some patients never need treatment for their CLL and it would be great if we could draw their blood and know exactly who they were because then they would never have to get any therapy or be exposed. For everybody else, if we had curative therapy, then we’d be giving it to everybody.
It doesn’t take away the anxiety or the worry, but you need to fill that with other things in your life.
If you have other chronic medical problems, like high blood pressure, diabetes, or heart disease, that you’re actively taking medications for, you’re doing something about it every day.
With CLL, if you’re not, you’re not. It doesn’t mean you don’t have a problem. You just don’t need any active therapy right now. It’s an important distinction and I wish people could think about things a little differently.
We need to couch it a little differently so patients can deal with it psychologically a little differently.
You may not be getting treatment for your CLL, but in a way, you’re actively treating yourself because you’re delaying the treatment that might be better when you need treatment.Dr. Adam Kittai on watch and wait
Jeff: Dr. Kittai, in your practice, what are the thresholds that get people out of watch and win?
Dr. Kittai: I want to validate all of the symptoms that patients have on watch and wait. It’s usually these low-level symptoms. I want to make sure that everyone knows that it is normal to have symptoms on watch and wait.
One of the studies that Bill mentioned was early treatment with ibrutinib versus placebo. The most surprising thing about this trial for patients who typically would have been on watch and win was that the patients who were randomized to placebo had a high symptom burden, higher than all of us expected.
It’s normal not to feel 100%. You may not be getting treatment for your CLL, but in a way, you’re actively treating yourself because you’re delaying the treatment that might be better when you need treatment.
For someone to require treatment based on a symptom, the symptom has to cause so much distress that it causes the patient to not have the ability to enjoy their life.Dr. Adam Kittai
Deciding When to Start Treatment
Dr. Kittai: There are two types of indications to treat. There are subjective factors, which are the symptoms, and objective factors, which are laboratory values and big lymph nodes.
The objective indications are hemoglobin, which is your red blood cells, less than 10 or a rapidly dropping hemoglobin, a platelet count less than 100, a spleen size that is larger than 6 cm below the left costal margin, and lymph nodes greater than 10 cm.
These objective indications are pretty extreme, I would say. I typically don’t let my patients get up to that level. We typically try to treat right before, but we see it coming. You do need to have one of those indications to treat.
The other indications to treat are going to be symptoms. Those are the classic B symptoms, like fatigue, night sweats, fevers and chills, and weight loss. These symptoms typically worsen as the objective signs worsen so they usually go hand in hand. Sometimes symptoms and objective indications are out of proportion so sometimes they’re a little discordant.
Every patient is a little different. For someone to require treatment based on a symptom, the symptom has to cause so much distress that it causes the patient to not have the ability to enjoy their life. I don’t like my patients to get to that point. I try to do it right before they’re miserable because I don’t think that’s fair.
Live life the best you can. I know it’s not easy, but get up every day and try to focus on something positive in your life.Dr. Jackie Broadway-Duren
Jeff: Dr. Jackie, we’ve been talking in a very clinical fashion about what’s going on with all the new stuff with CLL. “I was diagnosed five years ago and I’m still in watch and wait. I feel like I’m in limbo. What can I do to live normally and not think about it ever?”
Dr. Broadway-Duren: I know patients are worried and concerned. One thing I found helpful is to sit down with each patient and go through their prognostic factors.
They need to understand what their FISH test means. If you tell a patient you have a negative FISH, they look at you like you have two heads. But if you say to them, “These are the chromosome abnormalities that we look at for patients with CLL. You have no abnormalities,” that encourages them.
When you look at mutational status and other prognostic indicators, if all those things are favorable, talk with the patient and explain to them that it’s unlikely that they’re going to have a rapid progression of CLL. It doesn’t mean they won’t ever need treatment, but I think that helps allay some of the fears and anxiety that they have.
The only thing you can do is go about your life as best you can. Try to focus on other things, whatever it takes to keep you busy and keep your mind occupied.
The worst thing you can do is sit at home every day and get on Google and some of these CLL blogs. Some of them are helpful but some of them are not because of erroneous information.
Find a good factual website. Use LLS. If you want to hang out with people, get in with someone who has the facts and who will give you appropriate information.
Live life the best you can. I know it’s not easy, but get up every day and try to focus on something positive in your life.
Health maintenance falls into two categories. One is infection prevention, the other is early detection of other cancers.Dr. William Weirda
Dr. Wierda: Part of the challenge with watch and wait is that patients feel like they’re not doing anything actively for their health. I spent a lot more time in recent years talking about health maintenance.
Our patients are often living a normal life span as if they didn’t have CLL, but oftentimes we struggle with some challenges with the disease, even if they’re in remission. Their immune system doesn’t work normally.
Health maintenance falls into two categories. One is infection prevention, the other is early detection of other cancers because other cancers occur more frequently in patients with CLL than in the general population.
Infection prevention means making sure you’re up to date on all your vaccinations. It’s a very important area that patients can actively participate in.
Early detection for other cancers involves going to a dermatologist for regular skin cancer screening, annual mammography and pap smears for women, prostate cancer screening for men; and colon cancer screening. I would try to direct the conversation to that aspect because those are things you can do that are important for our patients.
The hardest part of starting an exercise program is the first step. The second one’s easy. The third one’s a piece of cake.Jeff Folloder
Jeff: Do the things that your GP wants you to do as well.
Take your blood pressure medicine. Take your cholesterol medicine. Keep your diabetes under control. Work on controlling your weight. Exercise a little more often.
The hardest part of starting an exercise program is the first step. The second one’s easy. The third one’s a piece of cake. Fourth, fifth, and all the rest of them are easy. It’s when you get up in the morning and know that you need to do whatever it is that you’re going to do. It’s taking that first step.
It’s really easy to sit in a chair or the bed and not take that first step. Sometimes all you need is one step so take that first step.
Take that first step with your happiness as well. Pick one thing. It doesn’t have to be big, but one thing that gives you the smallest first glimpse of a smile.
I have worked from home for well over a quarter of a century. Unfortunately, that means that the lines blur dramatically between my work life and my personal life. When I hear the email alert go off, I want to go see it.
At around 5 o’clock, I stop to go to the kitchen, grab a glass, and fill it with ice. Two four-footed furry missiles come flying into our den. I put a little whiskey in that glass, sit down in my chair, and turn on the evening news. Both cats sit right in front of me, waiting for their freeze-dried chicken treat. That makes me smile. That’s something that I can focus on. That’s worth doing.
I’m not focused on my CLL. I’m not focused on a cancer diagnosis. I’m not worried about my white blood cell count, my platelets, and how I sabotaged my glomerular filtration rate by not drinking enough water after exercising. I’m taking those first steps every day.
We know that watch and wait is not a fun way to live. What can we do about it? Make active approaches.
You can be unhappy. You can worry. Or you can find that one thing that makes you smile. You can go take that one step, and that one step turns into a block, and then that block turns into half a mile. Then the next thing you know, like me, you’re knocking out marathons.
We don’t use the word cure very often, particularly in CLL, because for most patients, their disease comes back. But there are patients who I’ve followed for 20 years whose disease hasn’t come back.Dr. Nicole Lamanna
Cure in CLL
Patient: How are you going to know when we’re cured? Is it going to be all physical symptoms good? Normal blood counts? Is it going to be a clonoSEQ of zero for two years?
Dr. Lamanna: There are some patients now who are theoretically cured. They might have gotten FCR, for example, or some other treatment modality, but the biology of their disease is so good that the disease never comes back.
We don’t use the word cure very often, particularly in CLL, because for most patients, their disease comes back. But there are patients who I’ve followed for 20 years whose disease hasn’t come back so they probably are cured.
Our technology is improving with how to measure minimal residual disease or microscopic CLL cells in your body to different depths of detection. We’re employing a lot of these techniques in the current clinical trials to look at depths of detection and it’s changing and evolving.
In CLL, it takes us longer to show if a treatment regimen is going to improve survival and ultimately cure because we’re going to be following some of this testing, which we’re doing on the clinical trials. These aren’t necessarily mainstream in clinical practice yet because the mode of detection is changing and we’re trying to put these in combinations with the clinical trials that are running. But we’re going to need a long time to show that a particular therapy might be potentially curative.
I’ll argue that depending on someone’s biology, there are, in theory, some of those patients already out there.
Jeff: You hedged that bet very well.
Hopefully, we get to a point where we have some biomarkers that tell us that someone is cured.Dr. Adam Kittai
Dr. Kittai: I’ve started using the phrase “functionally cured.” In a sense, it rephrases the thought process of cure. If you have somebody who’s on continuous therapy and they are not having any toxicities and their blood counts are completely normal, are they cured? They’re technically functionally cured. I like to say, “I looked at your labs and I wouldn’t know you had CLL if I didn’t know you had CLL.”
Dr. Lamanna: They may still have disease and die from something else.
Dr. Kittai: They’re chugging along on their BTK inhibitor without side effects and doing great. Isn’t that somewhat ideal as well? We don’t like the idea of having to take a pill every day, but to some extent, if you’re not having any side effects and your disease looks like it’s well controlled, I don’t know.
I wonder about the word cure. The easiest answer is we don’t know the answer to that question. Hopefully, we get to a point where we have some biomarkers that tell us that someone is cured, but I think that hasn’t been elucidated yet, even with our most advanced technologies.
More and more data is coming out that if we can’t detect your CLL, that is associated with a longer, progression-free survival and overall survivalDr. Adam Kittai
Jeff: Here we are at uMRD negative. If someone doesn’t show a single one of their cells in the count, are they?
Dr. Kittai: We don’t know the answer to that question yet. More and more data is coming out that if we can’t detect your CLL, that is associated with a longer, progression-free survival and overall survival, but we don’t know.
Anecdotally, based on another disease type entirely, chronic myeloid leukemia, we know that if you get a patient’s CML down to a low enough level, their immune system takes care of it. A similar concept with CLL is that maybe our immune systems can kick back in and take care of it when we get down to a lower level of detection that we’re just not detecting. We don’t know.
The word cure is tricky. Of course, we’re aiming for a cure. I hope that one day we have a biomarker that securely says this patient will not have a relapse again, they don’t need to be on medication, and they are not more immunocompromised than the general population.
The challenge here is assuming that being in remission and having undetectable MRD assures your immune system is back to normal, but we haven’t seen that.Dr. William Wierda
Jeff: Dr. Bill, you encourage people to do watchful waiting and careful surveillance and let you do the worrying. Patients are on watch and wait for an extended period. In general, people with CLL are considered to be immunocompromised, correct?
Dr. Wierda: Correct.
Jeff: The longer they’re on watch and wait, the longer their immunocompromised bodies are exposed to the world versus starting treatment so they’re not immunocompromised. How do you balance that?
Dr. Wierda: The challenge here is assuming that being in remission and having undetectable MRD assures your immune system is back to normal, but we haven’t seen that. We’ve done a lot of trials and have many patients who are still immunocompromised, even though they have undetectable MRD status. It takes a long time for the immune system to recover and restore to normal function.
Our future work at Anderson will be dedicated to figuring out things that we can do to accelerate the restoration of the immune function and the immune system. But right now, we don’t see that everybody’s immune system is totally normal even when they’re in remission or have undetectable MRD.
There’s a lot of ancillary work besides treating the disease itself to see how we can make things better for patients with CLL in terms of their immune system.Dr. Nicole Lamanna
Dr. Lamanna: There’s a lot of heterogeneity in terms of your immune system. Some people’s immune system is not as compromised as another person. We’re learning how to figure out which individuals might have a worsened immune system versus somebody else. Some CLL patients never get sick while there are patients who get sick all the time and that’s whether you’re on watch and wait or on active treatment.
There’s a lot that we need to learn in restoration and understanding the heterogeneity in our CLL patient population. You’re all different and not everybody is as immunocompromised as the next person. We need to find out if there are ways that we can help to augment their immune system.
Trials are looking at vaccines or at immunoglobulin in CLL patients to see whether or not they benefit and how we look at decreasing the incidence of infection. There’s a lot of ancillary work besides treating the disease itself to see how we can make things better for patients with CLL in terms of their immune system.
They are different tests that look at different parts of the cancer’s genetics to tell us how high risk the patient is.Dr. Adam Kittai
Dr. Kittai: A question I get often is how long will I be in watch and wait. There was one study that looked at three different factors: IGHV unmutated versus mutated status, palpable lymphadenopathy, and absolute lymphocyte count greater than 15.
If you had 1, 2, or 3 of these factors, how long would I be in watch and wait for? If you had three factors, typically it was around two years. If you had 2 or 1 factors, it was 2 to 5 years. If you had no factors, it was greater than five years.
I see a lot of people buck this trend, but at least it gives us an idea of what to expect. I hope that everyone bucks the trend, but at least it’s something that we can look at and at least advise our patients. If you have all three of these factors, most likely we’ll need treatment sometime in the next two years. If you have none of those factors, over five years is a time that you’ll probably be in watch and wait.
The prognostic factors that we look at in patients with CLL are IGHV mutated status, FISH, which stands for fluorescent in situ hybridization, cytogenetics, and next-generation sequencing. They are different tests that look at different parts of the cancer’s genetics to tell us how high risk the patient is.
Our normal white blood cells go through hypermutation where they get programmed to attack the very specific bacteria or virus.
Whether the CLL cell comes from the pre-program or after the program determines prognosis, which is interesting. If it comes pre-programmed, that’s IGHV unmutated and if it goes after the program, it’s IGHV mutated and is generally considered a favorable prognostic factor.
We look at all of these things together and help our patients understand their prognosis. A lot of that is changing with our new therapies. Some things that we thought were important are no longer important and some of the things that weren’t important are becoming more important. Your physician will help guide you about your risk factors in terms of what to expect for your prognosis.
Do not dismiss anything as being too trivial to discuss because everything is important. They need to know what’s going on. It’s important to communicate.Jeff Folloder
Jeff: Dr. Jackie, do patients confide in you? Do they tell you the truth?
Dr. Broadway-Duren: They do. Oftentimes, they will tell me or the advanced practice providers things that they don’t want to share with the doctor for whatever reason. Whenever I ask them, they are very truthful.
I want to tag on to what Dr. Wierda said as far as the immune system. I can think of several patients in our clinic who are in remission and still have all these infections so we’re giving them IV infusions of gamma globulin to try to boost the immune system.
Being in remission definitely does not indicate that you have an intact immune system right away. At some point, it may. The patients are very truthful and forthcoming with information when I speak with them.
Jeff: I advocate on behalf of all of the medical providers. When you’re in watch and wait, nothing is off the table. Everything must be on the table. Do not dismiss anything as being too trivial to discuss because everything is important. They need to know what’s going on. It’s important to communicate.
Vaccines and CLL
Patient: Dr. Wierda, is the shingles vaccine okay with CLL?
Dr. Wierda: You should not get the live virus vaccination for shingles. The one that’s used most commonly now, SHINGRIX, is not a live virus. It’s two doses separated by 2 to 6 months. You should not get live virus vaccinations if you have CLL.
In general, we favor continuous therapy for patients with deletion 17p.Dr. Adam Kittai
Patient: Ten years ago, the FISH test seemed to be a big deal and if one had 17p deletion, you didn’t have much time left. Is 17p deletion worse than anything else now?
Dr. Kittai: 17p is still one of our most important prognostic tests. The classic FISH testing that we do is deletion 13q, which is a good prognostic factor, deletion 11q, which used to be a bad one but now seems not to matter as much anymore, trisomy 12, which is intermediate, and deletion 17p.
We knew that patients who had deletion 17p on FISH did not respond well to chemotherapy. Our new agents work for patients with 17p.
In general, we favor continuous therapy for patients with deletion 17p. Not to say that you can’t get time-limited therapy with 17p, but it appears that 17p may matter more with time-limited therapy than it does with continuous therapy.
Typically, 17p goes hand in hand with TP53, which is done on next-generation sequencing. Sometimes they can be discordant. It’s pretty much the same thing.
In the clinical trials, when we talk about these combinations, we’re trying to see if these alternative strategies will be better in higher-risk disease individuals versus non-high-risk disease individuals.Dr. Nicole Lamanna
Dr. Lamanna: Patients who had these features were considered more adverse or worse, but these new targeted therapies have done great for those individuals.
In the clinical trials, when we talk about these combinations, we’re trying to see if these alternative strategies will be better in higher-risk disease individuals versus non-high-risk disease individuals. How do we tailor our therapies better depending on the features of your disease?
Patients with 17p and TP53 are doing so much better on these targeted therapies. They’re still important but compared to the chemoimmunotherapy days, folks are doing much, much better because of these targeted therapies.
Patient: What is the consensus on the RSV vaccine?
Dr. Wierda: I don’t think there’s a consensus yet. It’s a new vaccine. We heard a little bit of data at the International Workshop on CLL meeting. We need more data on its effectiveness in patients with CLL.
I don’t see a lot of drawbacks in giving it but we haven’t entered an era where we’re recommending it for every patient like we do for the flu shot. That may come, but because it’s a new vaccine and there’s limited data in the general population, there’s not any data available for us in the CLL community.
Even though there are risk-benefit ratios for everything you do in life, including side effects potentially from some vaccines, we don’t want you getting sick and being admitted to the hospital due to these infections.Dr. Nicole Lamanna
Dr. Lamanna: We think about vaccines because we’re trying to mitigate infectious complications in patients with CLL. In general, for many CLL patients, the immune system is impaired so your ability to mount the same type of antibody response to some vaccines compared to patients without CLL is generally not as good, but that doesn’t mean you shouldn’t get them.
The point is that you can get the flu shot and still get the flu, you can get the COVID vaccine and still get COVID, but if it diminishes the severity of those illnesses and prevents hospitalizations, that’s what we’re trying to do, right? We’re trying to give you any armamentarium that you might have to protect yourself from bacterial or viral infections that are running around so you’re not as sick.
One of the complications we see in CLL patients is infection — pneumonia, sinusitis, cellulitis, and hospitalizations. Infections and recurrent hospitalizations inhibit the quality of life. We have many patients who go through this day in and day out. We try anything we can use to diminish infections.
Vaccines may not be perfect, but we still recommend the COVID vaccine. Despite all the potential side effects, you should get the vaccine. We lived through 2020 and saw how bad it was. We saw how many people died. CLL patients had one of the highest mortality rates due to COVID.
Even though there are risk-benefit ratios for everything you do in life, including side effects potentially from some vaccines, we don’t want you getting sick and being admitted to the hospital due to these infections.
There is no evidence that the COVID vaccine causes CLL.Dr. Adam Kittai
Jeff: Dr. Kittai, I know the answer to this question, but I need for this to be reinforced in our community because it is a pervasive belief. There are a large number of patients who believe the COVID vaccine gave them CLL. Can you talk about why they think this?
Dr. Kittai: There’s no data to state that the COVID vaccine gave patients CLL. Honestly, it comes back to the statement that Dr. Nicole made. A lot of people think that they get the flu vaccine then they get the flu. Ultimately, when COVID was first happening, we were recommending our older patients to get the COVID vaccine.
Given that CLL is a disease of older patients, there’s going to be a chance that any older patient might develop CLL at any given time. It may have also been that someone may not have seen the doctor for a while, got COVID, went to go see the doctor, and finally had labs. Remember that CLL is usually diagnosed incidentally so it just might be timing, but there is no evidence that the COVID vaccine causes CLL.
Optimized Care & Limiting Side Effects
Jeff: Dr. Bill, some treatment protocols have side effects. How, when, and what do you communicate to the healthcare team? What information do you need to help mitigate what can be unpleasantness in CLL treatment?
Dr. Wierda: That’s a tough question. All of the treatments that we use have their own set of side effects and toxicities that we see more commonly than others. There are rare things that we don’t commonly see, even if we see a lot of CLL patients on a particular treatment.
Letting your care team know what’s happening, what’s new, what’s uncomfortable and concerning to you is important. Talk to your physician. It’s hard to say if there’s anything in particular because each treatment has its own set of toxicities so we look for different things depending on the treatment that patients are on. But as I mentioned earlier, most of these treatments are very well tolerated by patients and much better tolerated than chemotherapy.
Letting your care team know what’s happening, what’s new, what’s uncomfortable and concerning to you is important.Dr. William Wierda
Jeff: Watching other people go through it, chemo is not a pleasant experience. When I went through my clinical trial, which was a monoclonal antibody, my first day was not the suggested six hours of a few bumps. It was a full day of unpleasantness. Why is it that so many of these treatment protocols have a bad first day?
Dr. Wierda: What you’re referring to is mostly the CD20 antibodies. What we see is called the first infusion reaction. There is an immune component. You get a monoclonal antibody that binds to your leukemia cells and some chemical messengers are produced in your body. You get a fever and shortness of breath. The higher the white blood cell count, the more severe those reactions tend to be. It’s an immune reaction from the infusion itself that quiets down when the infusion finishes.
Sometimes people have a little bit of fever a day or two after their infusion because there’s not as much leukemia there. For the second infusion, those reactions are much less. We try to pre-medicate patients liberally with steroids to mitigate those, although we can’t always achieve that with steroids. But the subsequent infusions are less severe, usually because there’s less disease.
Jeff: We talked about secondary cancers or associated conditions. Everybody knows you’re supposed to be taking care of your comorbidities. One of the things batted around a lot in the support groups is that CLL patients should be seen by dermatologists regularly. What’s going on there?
Dr. Lamanna: Because your immune system isn’t as good, your body’s ability to surveil and prevent other things from happening is not as good as well. In addition to the infections, this can also play a role in increased risk of other cancers.
All of us are bombarded each day by different environmental stimuli in addition to our genetic components. If you have CLL, your immune system is more impaired so your body’s ability to overcome them is dampened.
There’s no doubt there’s an increased risk of other cancers. Skin cancer is one of the most common we see in CLL patients, mostly basal and squamous, although there could be melanomas as well.
If the dermatologist is following something, they’ll tell you if they want to see you more frequently. Listen to what they say, but at a minimum, see them once a year. If they find something early, they remove it and send it for pathology. We recommend it not just for dermatology but for other routine cancers as well.
Because your immune system isn’t as good, your body’s ability to surveil and prevent other things from happening is not as good as well. In addition to the infections, this can also play a role in increased risk of other cancers.Dr. Nicole Lamanna
Jeff: When should CLL patients be getting their colonoscopies?
Dr. Lamanna: Unless they have a family history, the age has shifted to 45. It used to be 50. We tell people to get their screening.
The point of a colonoscopy is to try to catch polyps. There is a lag time for most individuals on when polyps could turn into a malignancy. The goal is if they find those polyps, they remove them.
Generally speaking, if you have polyps, they’ll probably tell you to come a little sooner to get a repeat colonoscopy. Rather than 5 to 10 years, they might say 2 to 3 years. If you’re clean, they’ll probably say you’re good to go for 5 to 10 years.
I encourage my patients to do it a little sooner. The guidelines have shifted to 10 years if you’re clean. But if you have polyps, they’re going to want to do it sooner. The goal is to catch polyps early and remove them so that you don’t have a problem.
We recommend age-appropriate guidelines for other cancers. For folks who are much older, there comes a point in time where your utility of screening diminishes unless you’re high risk for a particular reason or you have a lot of polyps.
Some tests look at the DNA in the stool. For patients who have clean colonoscopies and are older or may have issues, doing a colonoscopy might be contraindicated for other reasons. There are other ways to screen people so we encourage you to talk to your docs about those, too.
Jeff: Are there any other conditions that CLL patients should be aware of other than the standard cardiac issues, high blood pressure, and diabetes? What else should we be looking at? Are we more susceptible to something else?
Dr. Kittai: Other things to think about are secondary cancers associated with treatment. For patients who have gotten prior chemoimmunotherapy, specifically with fludarabine or bendamustine, there is a risk of secondary myeloid leukemias that we have to watch out for so that’s why it’s also important not to stop following with your CLL doctor. Even if your counts are all normal and everything’s fine, you should still see a hematologist long-term to monitor for that and that’s going to be a simple blood count.
Other things that are associated with CLL include autoimmune complications. Most often, autoimmune complications coincide with progressive disease so that’s something that we follow. Autoimmune complications include autoimmune hemolytic anemia and immune thrombocytopenia or AIHA or ITP. We have to watch out for those as well.
Sometimes you can have complications that may happen down the road and your primary care doctor is not going to know how to manage those so finding a CLL specialist becomes very important.Dr. Jackie Broadway-Duren
Finding a CLL Specialist
Jeff: Dr. Jackie, we talk a lot about getting a CLL specialist. How do people get a CLL specialist? If you don’t live in a big city, how do you get a CLL specialist?
Dr. Broadway-Duren: You can always go to the LLS site. You can talk with your local oncologist whether they are CLL specialists or not, and they may be able to point you in the right direction or refer you to someone.
There are listings on the Internet where you can look up those things, particularly within certain hospital systems. Many times, patients are sent from the community. You can look it up or contact someone who is a CLL specialist.
Let me reiterate the importance of having a CLL specialist. If you come to Houston, we initiate you on therapy, say you’re doing well and we don’t need to see you as frequently, when you go back to your local areas, you need to have a specialist there, even just an oncologist in some cases.
Sometimes you can have complications that may happen down the road and your primary care doctor is not going to know how to manage those so that becomes very important.
If you don’t understand the disease process, it’s difficult to understand how to manage side effects from treatments. They may not be acute side effects but something that happens down the road. You need someone with the knowledge to manage that.
The problem lies in when you live out of town or out of state and we can’t examine you to make the appropriate choices on how to intervene. You need somebody knowledgeable enough to know how to manage these things.
Jeff: I’d like to shout out to the CLL Society. They have an Ask the Experts program that’s available. If you’re having difficulty finding a CLL specialist in your backyard, it’s a great place to start.
Telemedicine has created opportunities for all of us that didn’t exist before COVID so you should take every advantage that you possibly can to get a CLL specialist on your team.
Work with your care team, your mid-level providers, or the pharmacists to help with patient assistance programs.Dr. William Wierda
Cost of Treatment
Jeff: Our CLL specialists have talked about new treatments already here and coming down the pipeline. Dr. Wierda, how much do these cost?
Dr. Wierda: The new treatments are very expensive, without question. Most patients with CLL are in the Medicare age category and not all of them have supplemental insurance.
Medicare pays for 80%. Twenty percent doesn’t sound like a lot, but if you’re talking about $10,000, $12,000, $15,000 a month, 20% is a lot of money, particularly for patients on a fixed income.
There are a lot of patient assistance programs. The best recommendation to navigate the whole process is to work with your care team, your mid-level providers, or the pharmacists to help with patient assistance programs and opportunities that we have for patients to get the treatments that they need. There are a lot of them out there.
Mental health is one of the things that we really should focus on, especially for patients with cancer.Dr. Adam Kittai
Dr. Lamanna: When we’re about to initiate therapy for a patient, we will initiate that process on their behalf. We’ll prescribe and see if their insurance approves the medicine and what their copay is for the drug. We get that response back within a few days. We’ll sit down and talk if we’re going to go forward on a particular treatment based on that information.
If there seems like there’s a hiccup because of a large copay, the pharmacy team lets me know right away and they reach out to the patient to see if they can apply on the patient’s behalf to these assistance programs to see if they can get a reduction in the copay. We don’t start anything until we know and that we’ve all agreed that it’s okay.
Clinical trials are a different beast. This is how our European colleagues get a lot of the drugs they don’t have access to by getting their patients on clinical trials.
There are some patients whose copay is unreasonably high. It doesn’t happen often, but it does happen. We have to decide if that is a blockage to start a particular therapy or not. We have those conversations, but for most people, we do this behind the scenes before we start therapy.
Strategies for Coping & Living Well with CLL
Jeff: Dr. Kittai, how often do you interact with your patients on the mental health aspects of dealing with this disease?
Dr. Kittai: If I’m ever worried about a patient, I do engage. I work with a wonderful team of nurses, nurse practitioners, and a case manager. My case manager has a very bubbly personality. She knows all the things that she can help with. I usually ask her to go and talk to patients after I talk to them.
Mental health is one of the things that we really should focus on, especially for patients with cancer. In addition to telehealth with cancer doctors, telehealth with psychologists and psychiatrists is huge these days.
Be open and honest with your physician about how you’re feeling. Depression causes fatigue. That is one of the main things I screen my patients for when they’re complaining of increased fatigue that is disproportionate to the amount of CLL that they might have.
If you’re actively having depressive symptoms, if you’re struggling, you need to let your doctors know because there are things that we can do.
Jeff: I want to dig a little bit deeper into this because it’s such an important aspect. What is depression?
Sometimes just being able to talk about it is an immense relief so I encourage you to all be candid with your team about mental health.Jeff Folloder
Dr. Kittai: There are two screening questions I use for my patients. Would you describe yourself as being depressed? Typically, someone who has depression has thought about it. It’s not something that is not without mind.
Have you lost interest in the activities that you typically like to do? If you answer yes to either of those questions, there are more screening questions after. But if you have either of those things, I would seriously consider talking to your doctor.
The worst form of depression is suicidal ideation. I would say that if you have any concerns that you are feeling down and out and it’s related to your cancer diagnosis, there are certain things that we can do. There are programs that we have or have patients see psychologists and psychiatrists to help our patients through this.
Jeff: That’s good information. It’s good advice and good direction. Oftentimes, patients believe that there is a stigma associated with depression. If you are exhibiting any of those symptoms, if you loved playing catch with the dog and that doesn’t do anything for you anymore, let your team know. There are a lot of resources available. Sometimes just being able to talk about it is an immense relief so I encourage you to all be candid with your team about mental health.
To date, we have no supplements that cure CLL that I’m aware of. I’ve read no studies to support that.Dr. Jackie Broadway-Duren
The Role of Diet & Exercise in the CLL Journey
Jeff: Dr. Jackie, we have three basic groups in our patient support communities. We have patients who take an active role in their care. We have patients who just lay there and take it. Then we have patients who believe that they can diet and exercise their cancer into oblivion.
I worry about my diet and I worry about my exercise, but I’m not doing it to make my cancer go away. I’m doing it because I’m addicted to endorphins and I admit that freely. Let’s talk about diet and exercise. What is the role of diet and exercise in the CLL journey?
Dr. Broadway-Duren: We have patients who think that there are specific dietary supplements they can take that will help cure or treat their CLL. To date, we have no supplements that cure CLL that I’m aware of. I’ve read no studies to support that.
However, we do encourage patients to eat a healthy diet low in saturated fats. You want to eat healthy fats, such as avocado and grapeseed oil. Eating a diet that’s high in fat and carbs makes you tired.
Eat things within reason. I talk to people all the time about exercise and, many times, their response to me is, “If I’m already tired, how can I exercise?” Believe it or not, when you’re tired, just as Jeff said earlier, if you just get up and put one foot in front of the other, if you just walk from down your driveway maybe to the mailbox and back to the house, that’s a form of exercise.
Nobody has to run a marathon or do 50 laps in the pool every day. Anything that gets you moving and gets your heart rate up is going to be beneficial towards helping CLL and your overall body health in general.
Eat healthy. Drink lots of water. Any patient who comes to our clinic knows there’s a constant theme of hydration.Dr. Jackie Broadway-Duren
As far as supplements, several years ago there were some studies about green tea extract and its benefits, but I don’t know of any patients that were cured of CLL from green tea. I can’t argue against the fact that maybe it may be beneficial, but everything within reason.
When patients are in therapy, I try to tell them to stop all supplements because they’re not regulated. We don’t know exactly what’s in them and the quantity of what’s in them. We don’t know what’s going to interact with the drugs you’re taking for CLL and compete for that pathway where those drugs are metabolized.
Eat healthy. Drink lots of water. Any patient who comes to our clinic knows there’s a constant theme of hydration. They walk in the door telling me how many bottles of water they drank. All of us need to stay hydrated.
For patients who are on the venetoclax ramp-up, we are monitoring tumor lysis. We are monitoring your potassium levels very closely so that’s not the time to take one potassium supplement and think if one is good, three is better. We will tell you to lay off the potassium supplements at certain times during the ramp-up phase.
Disclose to your physician and team other alternative medicines you may be taking.Dr. Nicole Lamanna
Dr. Lamanna: I want to echo what Dr. Jackie is saying. I don’t want everybody to feel like the docs and the team are against supplements because it always comes off that we don’t believe in any other alternative medicine strategies.
To be fair, part of that may be a fault of the system. It takes funding to run clinical trials with alternative medications. Remember, some plant-based therapies have become cancer therapeutics. It’s not that we don’t believe in other therapies. It’s just that what may work for one cancer may not work for another cancer. When we talk about supplements, we haven’t tested them in the CLL community, outside of the trial of the green tea.
You must disclose to your physician and team other alternative medicines you may be taking. People don’t want to talk about it. Sometimes they feel that the doctors will get upset, but the truth of the matter is that they may have an impact on your organ function, like your liver and kidneys.
Supplements are drugs, too. Anything we take in has to be processed by our body. There may be drug interactions with other medications, even medications that have nothing to do with your CLL. It’s important to disclose anything you might be taking or considering taking so that your team can talk to you about the potential downsides, benefits, and so forth.
It’s not that we don’t believe in them. We want to keep you safe. It’s a conversation that needs to be held.
Everything in moderation. Battling cancer is hard in and of itself. The more that we take away things that we find joy in makes it even harder to battle the cancer.Dr. Adam Kittai
Jeff: Dr. Wierda, I love a good hamburger. Do CLL patients do better on a plant-based diet versus a meat-based diet?
Dr. Wierda: Not to my knowledge.
I love hamburgers myself, but I don’t eat hamburgers often because they’re not good for you. And I don’t have CLL. There’s a lot of fat in them.
Moderation is my keyword. I love French fries. I love onion rings. You can’t eat that stuff all the time. It’s not good for you.
A lot of it is common sense. There isn’t any diet that’s been shown to be beneficial for patients with CLL in particular.
Jeff: If a CLL patient is in watch and wait or in treatment, are there any vitamins that they should be taking, or should they just be focusing on eating good food?
Dr. Wierda: I take a multivitamin every day. Some things are helpful in terms of the regular multivitamins a day for patients with CLL and non-CLL patients.
Dr. Kittai: My general recommendation is the same. Patients who are healthier when they start treatment do better. If you come in in a healthier state, you’re going to do better. There is no food that we typically recommend.
Once again, it’s everything in moderation. Battling cancer is hard in and of itself. The more that we take away things that we find joy in makes it even harder to battle the cancer.
If you like a hamburger every once in a while, that’s fine. If that makes you happy, that’s fine. It’s not going to affect anything going on with your CLL. It’s a matter of keeping everything in moderation. Make sure that your health is as best as it can be because the healthier you are, the better you tolerate therapy.
Moderation should be the key. It’s not that you can’t have some dietary indiscretions, but it shouldn’t be all the time.Dr. Nicole Lamanna
Jeff: What about alcohol? I’ve joked around quite a lot about if my doctor ever says I have to give up alcohol, I probably will be getting a new doctor. That’s the way it is.
While we’re talking about stuff that we put in our bodies, I would like for Dr. Lamanna to address what I see thrown out on support forums every single day without fail. Sugar feeds cancer. Why do people persist in saying sugar feeds cancer?
Dr. Lamanna: If you have a lot of sugar in your diet, a lot of carbs, and a lot of other things that are not good for your body, you’re not taking care of your temple, and that leads to other medical problems. People who have diabetes are impaired in terms of healing because of their high sugars. It impairs their immune system and healing ability.
If you take care of your body and your temple, then you’re better able to deal with other medical problems or CLL therapy that goes with the territory because you’re a better fit and your organ functions better. There’s a lot online about how high sugar levels are bad for cancer. It’s not just bad for cancer; it’s bad for other medical problems, too.
Moderation should be the key. It’s not that you can’t have some dietary indiscretions, but it shouldn’t be all the time and that’s where that feeds into. I don’t like to take everything away from everybody.
Lowering your sugar and your potential of getting other medical problems are going to be important in how you fight off infections and cancers.
Jeff: Dr. Kittai, is there a connection between CLL and cholesterol levels?
Dr. Kittai: Correct me if I’m wrong, but I have not seen any connection between cholesterol levels and CLL levels. CLL mostly affects older patients. As we get older, we have more difficulty regulating our glucose and our cholesterol, and that just comes with aging and the American diet.
Ultimately, what it comes down to is to take care of yourself and your other comorbidities, and you should do better with therapy. But generally, there’s no link between cholesterol and CLL.
Jeff: Dr. Jackie, we’ve been talking about the fuel that we’re putting in our temple and taking care of the spiritual center of our temple, making sure our mental health is in order. Are there any other tips you want to share? How important is it for CLL patients and their caregivers to take charge of their bodies, take charge of their lives?
Mental well-being is as important and sometimes more important than physical well-being.Dr. Jackie Broadway-Duren
Dr. Broadway-Duren: It’s very important. We determine how we can cope with things. Sometimes our coping mechanisms are not 100%. You’re weighed down with, “I have CLL. They say I don’t need treatment yet, but that’s in the back of my mind.”
Maybe with the job you had, you’re not able to function fully anymore so you had to cut back on hours and now you have financial responsibilities that you have to worry about. Some people are already at retirement age so if you’re retiring with CLL, you’re not bringing in as much income so you can’t always afford to continue to do the things that you were doing.
If you’re having problems coping and you feel like you’ve just been weighed down, talk to someone. When patients come into the clinic, as Dr. Kittai alluded to, all of them are screened. The nurses screen them with a questionnaire every visit.
If there’s a patient who tells us that they’re having some problems coping or some suicidal ideations — and, yes, sometimes patients do — that’s an immediate call for help. We contact the social worker or psychologists and then psychiatry in some cases to get those patients’ immediate attention.
If you have somebody that you can confide in and talk to that can help allay some of that anxiety and depression, then do that. Speak to a licensed counselor. There are times when patients have to go on antidepressants or anti-anxiety drugs temporarily to get them through that immediate period.
Mental well-being is as important and sometimes more important than physical well-being. Their CLL status doesn’t matter if they’re at a point of wanting to commit suicide. That’s a very key fact that we have to address and do address. I encourage patients to always talk to somebody. If they don’t talk to you about it, then find someone who they can.
Jeff: Excellent advice.
Our relationship with our spouse and a healthy sex life is very important.Dr. William Wierda
CLL & Sex Life
Jeff: Dr. Wierda, you’re part of CLL Global. I would be remiss if I did not channel a part of CLL Global’s founder, Dr. Keating. Since you are here in his stead right now, you know that one of his big action items is his patient’s mental health.
Part of that is how they’re getting along with their significant other so I’m going to quote him. Let’s talk about sex. How important is a CLL patient’s sex life? How do we deal with it?
Dr. Wierda: It’s important for everyone. Something that you said in the very beginning resonated with me and that was that you have taken account of your priorities in life — who’s important to you and building relationships with those who are important to you. That’s a special thing and not everybody does that.
You don’t have to have CLL to do that. COVID helped with that a little bit, but perhaps we should take your advice on that and take account of what’s important to us.
Our relationship with our spouse and a healthy sex life is very important. We’re all human beings and although I blush about it, it’s just part of being a human being.
Jeff: It’s part of being a normal human being. If that part of your life is no longer normal for whatever reason, get some help. That’s what we’re talking about here. If something’s not working the way you want it to, get some help.
I ask the patient how they would like to bring other people into the conversation and who they want to share this information with, and then we work on that depending on each patient.Dr. Nicole Lamanna
Talking to Family & Friends About CLL
Jeff: How do we talk to family and friends about our CLL diagnosis? There are a million and one different approaches and strategies, and people believe one way is better than the other. What are some strategies for this?
Dr. Lamanna: First is the comfort level. Each patient is different. Some people have to get a handle on the diagnosis themselves first. Usually, when I have that conversation, I ask who they want to include in the conversation. Sometimes they’re ready to do that, sometimes they’re not and need a little time.
You can’t remember everything in one sitting. Oftentimes, I say, “Why don’t you bring your family member, your significant other, children if you want to?” If you can’t explain it, you can’t relay everything about your new diagnosis when you’re hearing half of it most of the time.
Oftentimes, I’ll suggest calling them on the phone or bringing them to the next consultation so I can explain things and if they have questions.
I ask the patient how they would like to bring other people into the conversation and who they want to share this information with, and then we work on that depending on each patient.
Depending on how old you are, that conversation can be tailored differently because some people feel they’re not ready to share with their extended family, their children, or people at work. People have different times when they feel comfortable and ready to include others. I do think that’s personal and different for everybody.
I encourage all my patients to let their kids know when they get this diagnosis because, ultimately, it’s important for them to know.Dr. Adam Kittai
When it comes to children, there are adult children and there are little children. When they’re little children, there are support groups that we can reach out to on the patient’s behalf, like CanCare. Different groups can incorporate how to do that with children.
Children don’t need to hear everything, but they are savvy. Even little children are savvy. They’ll get very upset not knowing because they do know something’s going on. They’ll be more upset about the fact that they don’t feel like they’re included. If they have little children, I encourage the patient by finding a forum to do this because I think it’s important for the child.
Dr. Kittai: As an older child with aging parents, one of the things that I’ve talked to my parents about was the concept of protecting me. I don’t know if everyone’s a little different, but trust me — you’re no longer protecting your kids from this diagnosis. You want your family to know what you’re going through.
At the end of the day, it’s your children who are going to be the ones helping you through all of this. It’s important to let them know if something’s going on as soon as possible, in my opinion.
This is something very personal to me. I encourage all my patients to let their kids know when they get this diagnosis because, ultimately, it’s important for them to know, they need to help if they can, and be supportive of you going through this process. The whole concept of protection because they’re better off not knowing, I think, is a total fallacy.
It also depends on the family dynamics… You have to look at the family dynamics and what type of relationship they have with family members.Dr. Jackie Broadway-Duren
Dr. Lamanna: There’s more hurt involved that way. Would you tell them that you didn’t have heart disease or diabetes? It’s the same concept. Most people know they’re taking medicines.
Your children want to know what’s going on with you. If they can be supportive, great. They may be supportive in ways that you never even could have imagined. I think it’s important early on.
Everybody does need a little bit of time to digest their diagnosis first, which I get, but I think it’s important to include others.
Dr. Broadway-Duren: It also depends on the family dynamics because, in some families, they’re not in that type of relationship to share with certain family members. When you talk to a patient over time, you get a sense of what the family dynamics are.
If it’s going to be more of a stressor for them to share this with their kids who may not be as supportive, then maybe they shouldn’t. It’s individualized. You have to look at the family dynamics and what type of relationship they have with family members.
I have a patient I’ll never forget. He and his wife thought they were doing the right thing for many years and didn’t tell their kids from when they were small until they graduated from high school. When they finally told them, they were very angry for a long time. I always encourage patients to talk to their kids and be honest with them, if they can.
When you get a CLL diagnosis, you have a unique opportunity in your life… CLL allows you to stop, figure it out, and take care of what’s important.Jeff Folloder
Jeff: Everyone has a different family dynamic, but for the most part, we have family members who deeply care about us and are deeply concerned about what’s going on. They may not always be able to express it well and you may not always be able to understand how they’re trying to express it.
My mother passed away shortly after I was diagnosed with CLL. She was dealing with Parkinson’s at the time. I have the very last voicemail she ever sent me. Whenever I need a little bit of centering and focus, I play that voicemail back.
She says, “Hello, Jeff, it’s your mother.” You could tell that her voice was creaky and that she was under duress and strain. “I need you to call me back. I need an update on your health situation. Love you. Bye.” I can’t get rid of that voicemail. That tells me that my family is important to me.
My youngest daughter asked me to serve as a mentor in her school and I’m happy to provide that service. When she has problems, she comes to me. I owe her the respect of letting her know what’s going on in my world and what I need from her. I do that with her sister and with her mother.
When you get a CLL diagnosis, you have a unique opportunity in your life. You can pull up the parking brake instantaneously and decide what it is that’s going to be important to you going forward. You can make the personal decision to get rid of the stuff that doesn’t matter. You have to determine if the juice is worth the squeeze. A lot of times, it’s not. CLL allows you to stop, figure it out, and take care of what’s important.
If you find that you have to take NSAIDs multiple times a day for multiple days in a row, that’s something that you really should let your doctor know about.Dr. Adam Kittai
NSAIDs for Joint Pain
Patient: Being on ibrutinib, I can’t take ibuprofen or naproxen. Tylenol is great but not strong enough for a lot of muscle-skeletal pain and I’m wondering if you have any recommendations.
Dr. Kittai: You can take naproxen and ibuprofen but not all the time. If you’re having severe pain, it’s okay to take an NSAID every once in a while, but it can increase the risk of bleeding and it can affect your kidneys. We don’t want patients on it long-term. We use a calcium-magnesium-phosphate supplement. It’s a triple pill that can help with joint pain associated with ibrutinib so you can ask your doctor about it.
If you’re having long-term pain, you should also be evaluated, too. I often send my patients to ortho. In addition, if we think the joint pain cause is ibrutinib, I switch to second-generation BTK inhibitors. You can dose reduce or do dose holds as well if the joint pain is directly related to BTK inhibitors.
The classic naproxen dosing is five days. I wouldn’t take it longer than that. If you find that you have to take NSAIDs multiple times a day for multiple days in a row, that’s something that you really should let your doctor know about.
Dr. Broadway-Duren: As far as joint pains, topical Voltaren gel has been shown to show benefits in patients. It’s over-the-counter. I’ve heard some positive outcomes with using that topical gel.
Jeff: Joint pain is a very common complaint in support groups. A lot of people report that taking Claritin helps with joint pain. What’s going on with that? I’ve never made the connection.
Dr. Lamanna: Antihistamines in general can help with the inflammatory response in your body. Even people who take vaccines and have reactions to vaccines take that, too, because it might mitigate some of the autoimmune inflammatory response.
Dampening this very hypersensitive immune drive that you have from CLL where you get exaggerated responses to certain medications, bug bites, and other things can be driven down sometimes with the antihistamines.
If you’re trying to stay healthier, it’s about maintaining your diet, not eating excessively, and not doing things excessively. The key is everything in moderation.Dr. Adam Kittai
Dr. Kittai: We’ve given short courses of steroids as well.
Dr. Lamanna: Figuring out if this is related to the drug or arthritis will help the doctors figure out how to best help you with certain supportive medicines or other referrals.
Dr. Kittai: Don’t be afraid if you get steroids and your white count jumps up; that’s a normal reaction. Every single time you get a steroid injection within a week of seeing your doctor, your white count will go through the roof. It’s a normal effect so don’t be worried. It will come down again.
Patient: Intermittent fasting is a big trend. Several of my family members do it and my son said, “If you fast long enough, your body starts to generate stem cells.” Could that be any help with our CLL?
Dr. Kittai: Not that I’m aware of. At the end of the day, diet and exercise is the key. Oftentimes, it’s hard to stick with a diet so I tell my patients to choose a diet that works for them.
Most diets are good because they limit caloric intake. If you’re trying to stay healthier, it’s about maintaining your diet, not eating excessively, and not doing things excessively. The key is everything in moderation.
Dr. Lamanna: If you’re fasting, make sure it’s okay with your other physicians in case you’re on medicines where you shouldn’t be fasting.
There probably is some genetic basis because there are multiple family members affected, but we just haven’t figured that out yet.Dr. William Wierda
Jeff: I have CLL. My uncle has CLL as well. Is CLL hereditary?
Dr. Wierda: There’s familial CLL where multiple family members have a diagnosis of CLL. It’s usually family members who are directly related like mothers, fathers, uncles, aunts, brothers, and sisters. Multiple family members are affected.
While 10% of patients with CLL have familial CLL, 90% are sporadic, meaning there’s not any family association with a diagnosis.
For a while, we’ve been interested in understanding the risk factors for familial CLL. What’s the genetics behind why family members develop CLL? We haven’t figured that out yet, but we’re interested in it. There probably is some genetic basis because there are multiple family members affected, but we just haven’t figured that out yet.
Jeff: Is there any group of people or ethnicity that may be more prone to this?
Dr. Wierda: There’s a high incidence of CLL among individuals who are of northern European descent. It’s very uncommon in the Japanese population. Those with an Ashkenazi Jew heritage also are at increased risk.
Dr. Lamanna: Sometimes, CLL may not be part of the familial CLL incidence, but there might be a more global issue in the family genetics, meaning a predisposition to cancers in general so CLL could be one of them.
When we first see patients, we often ask them about their family history to see whether or not they should be screened for familial mutations that might run in the family that might warrant genetic screening for other cancers.
Patients who have good disease control on BTK inhibitors can go without therapy for around 2 to 3 years.Dr. Adam Kittai
Dosing of BTK Inhibitors
Jeff: Dr. Kittai, the idea of reducing dosage or stopping the dosage for a BTK inhibitor. How does that work? What patients are candidates?
Dr. Kittai: I don’t know if everyone shares this opinion but now that we have the second-generation BTK inhibitors, which are safer than ibrutinib, I favor the second-generation BTK inhibitors when I’m starting patients on BTK inhibitors.
A lot of people who are on ibrutinib are asking if they should switch to the newer class of BTK inhibitors that are safer. I don’t typically switch if someone’s tolerating ibrutinib very well.
If someone has been dose-reduced on ibrutinib or if they’re developing symptoms due to ibrutinib, I switch. I have a low-threshold switch. I don’t mess with dose reductions anymore. I just switch patients to second-generation BTK inhibitors.
In terms of dose reductions on second-generation BTK inhibitors, it depends. If I’m starting therapy, usually within the first year, I try to maintain the dose as best I can and treat side effects that might be associated with the drug.
In general, we can reduce the dose. I try not to do it in the first year but that depends because I’m trying my best to get as good disease control as I can. That’s an overall sense, but there are exclusions to that. Talk to your provider about when a dose reduction is appropriate.
Another question is if a patient on BTK inhibitors for several years can stop. I’ve done this in one patient who had undetectable minimal residual disease. She was fed up with taking her BTK inhibitor. She’s still doing well. We now have some data that shows that that is something that maybe we should be considering.
We know that patients who have good disease control on BTK inhibitors can go without therapy for around 2 to 3 years. I also have had patients that buck that trend as well. These numbers are not absolutes. These are all averages and medians so some people may not have 2 to 3 years and some people have much longer.
There was data presented at iwCLL where they stopped patients’ ibrutinib who had good disease control and measured the amount of disease that came back over time. Most of those patients one year out of stopping had stable disease.
This is something that’s coming. In select cases, I would consider it as I have done but talk to your physician about that if that’s something that’s right for you.
In general, if you’re healthy and you’ve been vaccinated, you can’t go through life being worried about every little thing every minute. Use caution.Dr. Jackie Broadway-Duren
Exposure to Infections
Jeff: Dr. Broadway, a patient asks, “I’m afraid to go to restaurants and other crowded places. Should I be worried?”
Dr. Broadway-Duren: I am.
Here’s the deal. For patients who are on therapy and maybe neutropenic, meaning your absolute neutrophil count is low, less than 1.0, then yes, you should have some concern about being out and about eating at restaurants and so forth.
I try to not recommend or even discourage patients from going to these all-you-can-eat buffets. Pay attention to what people are doing before they reach for those ladles. I strongly discourage them from eating at buffets, as I don’t myself routinely.
If you’re neutropenic, you may want to limit your outings. That would probably be a time to pick up something and eat at home or avoid being around a crowd of people anyway.
In general, if you’re healthy and you’ve been vaccinated, you can’t go through life being worried about every little thing every minute. Use caution. Avoid areas where people are sick. Avoid being in direct contact with them, but use good handwashing and a lot of common sense.
Richter’s transformation is extremely uncommon among patients with CLL who haven’t had treatmentDr. William Wierda
Jeff: Dr. Lamanna, are there warning signs for Richter’s transformation?
Dr. Lamanna: Richter’s transformation is transformed from your CLL cells. Sometimes they can change into a more aggressive lymphoma. The most common happens to be what they call diffuse large B-cell lymphoma, but some other transformations can occur such as Hodgkin’s disease and prolymphocytic leukemia.
Back in the day of chemoimmunotherapy, patients presented a lot sicker in general. They would have fevers and chills, loss of weight, and feeling very unwell. That still can happen, but with the targeted therapy, sometimes the transformation can also be more subtle.
Not everybody is very ill when they present. Maybe it’s profound fatigue that seems out of proportion to the rest of how they feel. They might be currently on a drug, but they’re having profound fatigue. If we haven’t found another reason, that would be a reason for us to look.
Sometimes people still get fevers, sometimes their LDH is rising. The presentation is not as classic in my experience.
There’s more of a mix in presentation than when we only had chemoimmunotherapy and patients were much sicker. We still have some patients who present very sick, but there’s a range in how they present.
Most of the CLL community is working on collaborating and trying to develop new and more effective treatments for Richter’s transformation.Dr. William Wierda
Dr. Wierda: Richter’s transformation is extremely uncommon among patients with CLL who haven’t had treatment. That situation is probably another disease and not something that has arisen from the CLL. We can cure those patients of their Richter’s transformation typically with chemotherapy.
Most of the time, Richter’s happens in patients who’ve had treatment and it’s from the malignant cells and the aggressive cells that have arisen from the original CLL. In those cases, they’re a lot more resistant to treatments and more difficult to manage.
It’s an area of unmet clinical need for us and an area of active research. Most of the CLL community is working on collaborating and trying to develop new and more effective treatments for Richter’s transformation.
Quality of Life of People in Watch & Wait Who Don’t Need Treatment
Jeff: Some patients get diagnosed with CLL, they’re on watch and wait, and then they go on to treatment. Some patients will never need treatment. What percentage of the population is that and what’s their quality of life?
Dr. Wierda: I think it’s exceedingly good. They still can have infections. They still can have other cancers more commonly than the general population. But in general, the disease isn’t growing. It’s not causing any problems. They’re not getting anemia. Their platelet counts are normal and they live a relatively normal lifespan.
In my experience, probably overall it’s 20%.
Jeff: Interesting. I would have thought it would be closer to 100%. I’m surprised to hear 20% don’t need treatment. I would have thought that most CLL patients at some point would need treatment.
Our patients with CLL are living very close to the normal life expectancy, even if they require treatment with our new therapies, which is great news.Dr. Adam Kittai
Dr. Lamanna: But the counter, I think, is often the way it’s described. Since most people are diagnosed incidentally by their primary care physician or if they’re getting screening for surgery or mammography, they’re picked up routinely. The docs will often go, “Ah, you have CLL, it’s okay. You’re going to die of something else.”
The fact is that the majority of patients do need therapy for their CLL. It’s not the benign disease that everybody talks about when you hear from other doctors not to worry about it. It’s a small percentage of patients who don’t need treatment; the majority do.
One of the first things I do when I see somebody with a new diagnosis is counseling them that 20% likely don’t need treatment, but the majority at some point do. I’d rather you think that you might be one of those. We can talk about the ones that we think are in that 20% group, but that doesn’t mean we have a perfect test that identifies them. Even if you’re a good risk, I wish I could say that they never need treatment but that’s not the case.
Dr. Kittai: To add to that, one of the questions I hear is the average age of death of CLL patients. There was an interesting study that was presented at iwCLL that looked at all patients who were treated in modern-day clinical trials. These are patients who require treatment. They did a study where they took all those patients and matched them to age-matched controls in the general population. The overall survival of the two groups was practically equal.
With treatment, patients were getting very, very close to their life expectancy. Remember, these are all clinical trials so it’s going to seem a little bit low. It was 52 to 55 months versus age-matched controls which was 56 months. Once again, it was age-matched controls so they matched the population to age-matched controls to general society and the difference was only by a few months. That tells us that our patients with CLL are living very close to the normal life expectancy, even if they require treatment with our new therapies, which is great news.
I’ve seen a patient go into spontaneous remission. My point is to be hopeful.Dr. Adam Kittai
Dr. Wierda: Again, you have to factor in the age component to that. For patients over 65 or 70, we’re achieving probably a similar survival as the non-affected, age-matched controls in the population. This group tends to see younger patients because we’re at academic centers and referral centers so we see young patients.
I have a 17-year-old with CLL who I’m treating now. For that patient, even though we have great treatments, we need a curative treatment, perhaps a stem cell transplant. The life expectancy for a 17-year-old is going to be different compared to an 80-year-old so you have to consider that also.
Jeff: That’s an astonishing bit of information. I had never heard of a CLL patient that young.
Dr. Kittai: One more astonishing thing I’ve seen is someone going into remission without any treatment. I’ve seen a patient go into spontaneous remission. My point is to be hopeful.
Patient: Dr. Wierda mentioned stem cell transplants and I was wondering what work is being done in that area.
Dr. Wierda: Not a lot because we’re not using it as much as we used to. In the last two years, I’ve probably sent two patients for stem cell transplants. Thankfully, we’re not having to utilize it as often as we used to when we were using chemotherapy.
We’re much more enthusiastic and interested in CAR Ts. There is research work with cord blood-derived CAR NK cells. Those are cell-based strategies that may ultimately take over the allogeneic stem cell transplant where you’ve got a donor that you’re doing a transplant with.
We are now in an era where we take a pill a day to keep our cancer away. We couldn’t have said that 10 years ago.Dr. Adam Kittai
Jeff: We have covered a ton of information. This has been great. I love having these sessions. They fill me with hope. It helps me get my message that you absolutely could live a great life with CLL.
What’s one message you want them to hear loud and clear that you could not say a decade ago?
Dr. Wierda: A cure is soon to come. We couldn’t have said that 10 years ago. I remember going to a meeting with a CLL research group that we were collaborating with. Somebody brought up the word cure and one of my colleagues said, “How can you say that? We’re nowhere near a cure. That’s not something we even need to talk about.”
I thought about it at the time and reflected on it. It was before we had ibrutinib or venetoclax. That comment today would not at all resonate with anybody because I do think we have the tools to cure patients with CLL.
A cure is on the near-term horizon for us. We just need to figure out how to use the drugs that we have available now and optimize them to cure patients.
The issues of Richter’s should subside and go away. The issues of refractory disease should go away. Ultimately, and hopefully in the distant or not too-distant future, the stress and concern about watch and wait will go away because we’ll be talking about curing patients with well-tolerated treatment, and watch and wait will be a thing of the past.
The good news is that from where we came from with chemoimmunotherapy… There’s a lot to be hopeful for.Dr. Nicole Lamanna
Dr. Lamanna: Targeted therapies have transformed the way we care for patients. We need to figure out ways to tweak the therapies. We have a whole bunch of new players coming in the mix and that will impact many patients who have relapsed on BTKs and venetoclax.
There’s a lot of hope for the relapsed population as well. There’s a lot of work that needs to be done. Despite these therapies, we have to figure out ways to improve people’s immune systems. There are still a lot of side effects and infectious complications that we need to work on.
It’s different from when I started. The good news is that from where we came from with chemoimmunotherapy, the side effects, the issues we used to see, and the limitations, there’s going to be a lot more personalization of some of these medications with different subgroups of characteristics of patients within CLL. There’s a lot to be hopeful for.
Think about your blood pressure, your weight, your diet, and all of these things that you need to maintain a healthy lifestyle. Continue to thrive in every aspect of your life.Dr. Jackie Broadway-Duren
Dr. Kittai: At the end of the day, we are now in an era where we take a pill a day to keep our cancer away. We couldn’t have said that 10 years ago. Not only are these pills effective, but they’re getting safer and safer and safer and that is a really exciting thing for our patients with CLL.
Dr. Broadway-Duren: I want to focus on the patients who are in the watch and win category. I want you to think of the analogy of an elephant in the circus. The elephant is the center of all the animals and they’re the largest animal. But other smaller animals around the elephant need to be taken care of.
Think about your blood pressure, your weight, your diet, and all of these things that you need to maintain a healthy lifestyle. Continue to thrive in every aspect of your life so that you’re not so consumed with feeding the large animal, the elephant. All of the animals need to be fed and cared for.
With that being said, I 100% concur with everything that’s been said. I’m excited about the future of CLL and can’t wait to see what’s next.
A cure is on the near-term horizon for us. We just need to figure out how to use the drugs that we have available now and optimize them to cure patients.Dr. William Wierda
Jeff: I want to thank each of you. Thank you to our doctors.
Everyone in the CLL universe needs to know that progress is being made. I’m hopeful that we are making progress and that the future is indeed bright.
I would like to thank the CLL Global Research Foundation for putting effort and resources in the pipeline to find a cure.
I’d like to thank MD Anderson for taking great care to make sure we have a venue to witness these things.
The Leukemia & Lymphoma Society does an awesome job of education and patient support. They provide so many resources that most of us are unaware of all the good that they can do.
I am constantly referring patients and caregivers to their patient support programs. They’ll help you with your copays, your transportation, and a myriad of things. They print out brochures and information so that you can have a handy guide when you want to figure out what questions to ask and how to get through particular things.
I thank them for their support during my journey and I hope that you’re utilizing LLS as part of your resource package.
I’d like to thank the CLL Society. Dr. Kaufman is providing wonderful resources all across the globe for anyone who asks. These are great people.
I also want to give a big thank you to a local organization in Houston, CanCare. Most cancer support organizations provide help and group support. CanCare approaches things completely differently.
When you call CanCare, you’re interviewed and matched with someone who’s just like you. Whether you’re a cancer patient or a caregiver for a cancer patient, you’re matched with someone and you get to walk that journey with someone who’s been there.
I’ve been a CanCare volunteer for quite some time. It’s incredibly rewarding to talk to someone who’s been recently diagnosed and explain to that person, “We’ll get through this. We’ll figure out a way to get this done.” It’s a unique approach.
They’re a nonprofit that exists exclusively upon the kindness of strangers. For 33 years, they’ve been providing this wonderful support in Houston and other communities across the country. I appreciate the fact that they’re here today.
I’d like to thank CanCare for providing shoulders to lean on and for anyone who needs to get matched.
I would also like to thank our sponsors, AbbVie and BeiGene. When companies like AbbVie and BeiGene sponsor events like this, they do it with absolutely zero editorial control. They know that these types of interactions are not just important for the CLL community, they are crucial for the CLL community. They want the word to get out.
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I wish you well. Go live a great life.
Everyone in the CLL universe needs to know that progress is being made. I’m hopeful that we are making progress and that the future is indeed bright.Jeff Folloder