We want to thank The Leukemia & Lymphoma Society for its partnership in this program. The LLS offers incredible free resources, including their Information Specialists as well as their Clinical Trial Support Center, both of which provide one-on-one support in different areas for the blood cancer community.

We also want to give a shout-out to our friends over at The CLL Support Group on Facebook led by our friends, including our moderator Michele Nadeem-Baker. They offer ongoing virtual support for folks dealing with a CLL diagnosis.

Treatment Advances in CLL

Michele: Doctors, the world of CLL has changed tremendously with so many more treatment options. Dr. Lamanna, can you give us a summarized update on the current CLL treatment landscape and how it’s changed, especially in the last couple of years?

Dr. Lamanna: To allude to what Michele was saying, back in the day, we had chemoimmunotherapy regimens like fludarabine, cyclophosphamide, and rituximab or FCR, or bendamustine-rituximab intravenous therapies. These were standard of care. We didn’t have as many choices.

Now we have more of these targeted small molecule inhibitors. The two big classes we have are BTK or Bruton tyrosine kinase inhibitors and BCL2 inhibitors. These oral therapies have become the standard of care. Patients can either take a chronic therapy with one of these oral BTK inhibitors or you can get a time-limited approach with a BCL2 inhibitor.

The only one we have currently approved is venetoclax in combination with a CD20 monoclonal antibody, which is rituximab or obinutuzumab. We’ve moved away from chemotherapy and now people are on either BTK inhibitors or some sort of venetoclax-based therapy.

Shared decision-making is a collaborative process where patients—often with their family members—and their doctors sit down, communicate, and come up with a plan.

Dr. Charles Farber

What is Shared Treatment Decision-Making?

Michele: I’m extremely thankful for all of these new treatments, but this means choices, and choices mean decisions need to be made. Many patients are hearing the term shared decision-making. What does that mean?

It’s understood that doctors are the experts from a medical and clinical standpoint, and patients are the experts on themselves and what matters most. Dr. Farber, please explain in simple terms what shared decision-making means when it comes to treatment and what the process typically involves.

Dr. Farber: Shared decision-making is a collaborative process where patients—often with their family members—and their doctors sit down, communicate, and come up with a plan. It’s not limited to a choice of treatment or duration of treatment. With CLL in particular, most patients don’t need treatment, so we observe them. We do watchful waiting or as my patients refer to it, watchful worrying.

The first decision is what criteria need to be met before a treatment is offered. Then we discuss what treatment options are available, what are they, and what’s best for the particular patient. It’s individualized, so it relies on two-way communication where the doctor may have in mind what’s best for the patient, but the doctor doesn’t make the decisions for you.

We do share in the decision-making where it’s appropriate. It boils down to trying to communicate and impart important information to our patients and their loved ones to determine what’s best. It’s interactive. It’s a dialogue. The doctor with their experience and knowledge has to work with the patient with what they desire.

What Factors Guide Shared Decision-Making?

Michele: Dr. Lamanna, what factors guide you in making treatment decisions?

Dr. Lamanna: This has become more complicated and part of it is because shared decision-making has become more present because we have more options. When there was only one option, the choices were whether the patient was going to do treatment or not. With all these options, it becomes a conversation.

We do shared decision-making because these treatment options are slightly different… what may be relevant for them at this particular moment in their life may be different later on down the road.

Dr. Nicole Lamanna

We think about the genetics and the disease itself. What is going on with the patient? What are the features of their disease? Are their blood counts bad? Do they have big bulky lymph nodes? Do they have genetic features? Do they have chromosomal abnormalities? Do they have high-risk disease? You might hear about 17p deletion, TP53 mutation, or even multiple chromosomal abnormalities.

What other medical problems does the patient have? What other comorbidities do they have? How is their kidney function? What are their social circumstances? Can they get back and forth to the clinic or the hospital frequently or not? Do they need extra support? Are we looking at therapies that might be easier for that patient?

We take all of those into consideration and that’s where shared decision-making comes into play when we talk about either BTK inhibitors or venetoclax-based therapy. What are the choices in that person’s life at that particular time? Some people might have little kids and are busy and active, so they need something simple and not going to be too labor intensive. Other people may choose something different and go for more intensive therapy because they can put in the time.

We do shared decision-making because these treatment options are slightly different. They’re both great treatment options. Even though many people will wind up potentially using both of these options during their lifetime, what may be relevant for them at this particular moment in their life may be different later on down the road. That’ll come up again when you talk about relapse or needing more therapy.

Balancing Treatment and Quality of Life

Michele: Dr. Farber, quality of life is an important factor for all patients when considering treatment options. How do you balance the potential benefits of treatment with the impact on a patient’s daily life?

Dr. Farber: It’s a very complex equation. I saw a physician newly diagnosed with a low-grade lymphoma. I asked him if he was retired, about his personal life, and what he enjoys doing. He was with his wife and family. The wife interrupted and asked, “Why are you asking these questions?”

I told her it’s very relevant in terms of the big picture. What are the goals of treatment? What’s the lifestyle of the patient? What are they willing to tolerate? How temporary is the initial treatment? Is it a phase? Some of the medicines require more intensive monitoring before things get better, so the questions are very important.

Quality of life is a very important issue and one of the more important variables in the treatment equation.

Dr. Charles Farber

Quality of life is life. Whether someone is willing to sacrifice, people want to live longer and better, and what they’re willing and able to tolerate and for how long has to be assessed. It’s a very complex equation and with these many variables, it needs to be explored.

What are the goals of therapy? Is it to make you live longer? Is it to make you live better? What are we trying to achieve? What are the treatment options? What are the side effects? Quality of life is a very important issue and one of the more important variables in the treatment equation. Shared decision-making is critical where you can’t do for the patient what you think is important. It has to be a dialogue.

Michele: All this is music to my ears because when I was on frontline treatment, my quality of life wasn’t so great, but at that point, there were no choices. We are so fortunate to have these choices now and that we can have a better quality of life as CLL patients.

Approaches to Treatment

Michele: Dr. Lamanna, what are the potential advantages and disadvantages of a fixed-duration treatment versus a continuous treatment?

Dr. Lamanna: Both treatment options are great and because we have these excellent options, we talk about the logistics, the advantages and disadvantages of going for either approach, and then we align that with what’s going on with the patient at the time in their life.

Unless there’s something glaring, like a comorbidity or medical problem where I think one drug might be better than another, then I’ll still discuss both agents, but I’ll bring up my concerns and what I think they should do. You have these discussions and factor in what their wishes are.

We teach everybody that if you’re taking BTK inhibitors continuously, some of these nagging side effects can occur later because you’re taking this indefinitely unless you have a side effect or your disease progresses. The downside is you could have some uncomfortable side effects, like diarrhea, GI issues, cardiac issues, bleeding, and bruising.

The benefit of venetoclax-based combinations is that it’s time-limited. It’s very similar to what we used to do with chemoimmunotherapy where you’re getting a short duration of therapy and hopefully won’t need to be on treatment until many years down the road.

The downside is that it’s more labor-intensive in the beginning. There’s a lot of monitoring because your blood counts can fluctuate a little bit more commonly with the combination. Sometimes you need extra help. They might have dose modifications. There are different logistics with a time-limited approach that people have to be willing to commit to, but the advantage is you get a break from therapy.

I have both of these conversations with patients because it is rare to say that somebody is precluded from one regimen versus another and that’s why most patients have an option. There might be some circumstances based on comorbidity, cytogenetics, or other issues that I’m concerned about with where I might recommend one approach versus another, but we have that dialogue.

Michele Baker: Dr. Farber, is your approach different and if so, how?

Dr. Farber: No, it’s very much in line with Dr. Lamanna’s. I would echo what she said that BTK inhibitors are very easy to start and hard to continue whereas the BCL2 inhibitor venetoclax is very cumbersome to start and requires a lot of initial monitoring. The patient has to come in very frequently for lab work and hydration as we’re ramping up, but it’s easy to continue.

Treatment has to be individualized. There may not be a perfect treatment, but one clearly may be better than another.

Dr. Charles Farber

With ongoing treatment versus finite treatment, the majority of people would like to be treated with finite therapy for one or two years, but that’s not for everyone. It’s a little counterintuitive, but some people feel very comfortable being treated with ongoing therapy because they feel like they’re proactively being monitored and treated.

A lot of people panic when it comes to the end of the year or two years on venetoclax and they become concerned about what we’re going to do next. It’s not broken. Why do we want to fix this? What’s wrong with continuing with venetoclax?

Shared treatment decision-making is individualized. Comorbidities, age, and ability to come in frequently in those first few weeks may dampen my enthusiasm for venetoclax in certain individuals. If they’re on an anticoagulant or blood thinner, I worry about that with BTK inhibitors.

It’s truly a situation where the treatment has to be individualized. There may not be a perfect treatment, but one clearly may be better than another. There’s a lot of information. CLL patients tend to be older and have comorbidities, so Michele, you are quite the exception. But you do the best you can. It requires a lot of patience, but it’s very gratifying.

We’ve had amazing treatments historically. If you look back 10 or 15 years ago, it was prehistoric, particularly for patients at higher risk with unmutated, immunoglobulin-heavy chains or TP53. We had no treatment until the advent of ibrutinib. It’s a very gratifying time to be in practice where we have options and we can talk to patients about what may be better for them.

Bridging the Gap: When Patients and Doctors Disagree on Treatment

Michele: What happens when a patient and their doctor have differing views on a treatment plan’s next steps? What do you do?

Dr. Farber: To some degree, the patient’s always right. If you feel they’re taking a misstep and if it’s not a horrible misstep, you voice your concern. If it’s something terrible to you, tell them you’re not willing to do it or perhaps they should seek an additional opinion. You try to resolve it.

The C in CLL is chronic. If they want to take ivermectin or something unproven, you try to educate them. You try to intellectualize. But it could be difficult because some patients get an idea and it may not be a good idea, but they feel very strongly about it.

If it’s something you’re uncomfortable doing, you can try to excuse yourself and offer a second opinion. It could be challenging and some patients get offended when you don’t do exactly what they’d like you to do. They could come at you with something from Dr. Google that isn’t necessarily appropriate. You have to be calm and try to explain the rationale for why you think it may not be a great idea.

Michele: What you would say to someone exactly if they brought up ivermectin?

Dr. Farber: I tell them that there have been anecdotal reports of patients doing well with various diseases, but that’s not scientific and doesn’t prove that ivermectin is effective in a given setting. I explain about randomized prospective trials. The best way that this is done scientifically is to take a group of patients and divide them into two or more groups. One group is treated with the test agent and the other is treated with standard therapy, placebo, or under observation. The true scientific way is if the group that gets ivermectin does better, lives longer, has a better quality of life, and has objective improvements in their labs or radiographs, that is scientific.

Sometimes in CLL and other diseases, there are spontaneous remission improvements. Single cases of patients getting better is akin to snake oil where someone comes up and endorses a treatment. That’s what I would I would try to explain. I try to explain that individuals getting better on ivermectin is not akin to a randomized prospective trial showing clinical benefit.

Michele: You’re very polite with your explanation and what you would say to someone about ivermectin. I appreciate that. Dr. Lamanna, what would you do if you and a patient disagree about what their treatment plan will be and their next steps?

Dr. Lamanna: To be fair, it is a dialogue. I’ve been fortunate that there aren’t many patients who I’ve had real troubles with. Thankfully, many patients either want to hear the whole discussion or read and bring up their questions with me and that helps the dialogue because you hear where they’re coming from.

If people bring up things that are completely not standard of care, then I have a discussion with them on the standard of care and about supplements or alternative medicines and how to integrate those into current practices or therapies that might be needed for their leukemia.

If somebody doesn’t want to take any standard of care treatment, then I’m probably the wrong person for them. It’s not difficult to have that conversation because either the patient is a right fit and doesn’t want to have anything, is afraid to take any kind of standard of care therapy for CLL, and that’s very easy to have the discussion and see where they want to take that.

Another conversation is when people get multiple opinions from different doctors. We see patients who talk about different therapies and they’re usually talking about all the standard of care therapies. The discussion now shifts to treatment sequencing. Should they do this one first or that one first?

Another discussion is talking about the different clinical trials and that’s great because that’s an open dialogue and right up my alley. I’m happy to talk about any of that, share my knowledge and expertise, and come to a mutual agreement if they want to do one or another, whether with me or someone else. I’ve never had too many difficulties where we’ve disagreed or where it’s been not approachable. It’s something that we have a conversation about.

You want to partner with a doctor and a team that fits you. I may not be the right person for that person all the time and that’s okay. I respect that.

Dr. Nicole Lamanna

I always say to patients that because CLL is a journey, you need to find somebody that you feel comfortable partnering with. That may not be me and that’s okay. It’s a long journey and they’re with you for a lifetime. You hope that they’re with you for 20-plus years or more. Hopefully, they will have a normal lifespan. That’s what we’re shooting for with all our research. You want to partner with a doctor and a team that fits you. I may not be the right person for that person all the time and that’s okay. I respect that.

Michele: It’s a long-term relationship and it’s important that you and your doctor gel. I always say it’s almost like dating, trying to figure out who’s right. My relationship with my CLL specialist is probably one of the longest I’ve had; not quite as long as with my husband but almost.

Beyond Initial (Frontline) Treatment

Michele: Let’s move forward to second-line and third-line therapy. Dr. Lamanna, what factors do you consider? Are they different when selecting a second-line therapy and planning for future treatment options?

Dr. Lamanna: This is a journey. Although most patients are focused on their first treatment and what they’re getting at that moment, I’m always thinking about their next lines. The goal is to try to think ahead.

What they got in the frontline and what their response duration was to that therapy will play a role in what they’re going to be recommended in the second or third line.

Dr. Nicole Lamanna

In the second or third line, you consider several factors. What did they get in the frontline? Have the genetics of their disease changed? Were they once a favorable risk and now changed to 17p deletion or TP53 mutation? How did they tolerate their first regimen? Do they have new comorbidities or new medications that we have to be concerned about? What they got in the frontline and what their response duration was to that therapy will play a role in what they’re going to be recommended in the second or third line.

If they got a time-limited approach with a venetoclax-based regimen, like venetoclax-obinutuzumab, how long did that last? Was it short? Was it long? Did they tolerate the regimen? Is that something we can reconsider? If they were on a BTK inhibitor for their frontline treatment, then we’re not going to offer them another covalent because most people at this point have gotten covalent BTK inhibitors in the frontline.

How to sequence these drugs is still being evaluated. The point is it’s important to know what they had for frontline therapy.

Dr. Nicole Lamanna

If they’re continuously taking a medicine, you’re not going to switch them to the same class of covalent BTK inhibitor. You’ll likely go to a venetoclax-based regimen. We have a non-covalent BTK inhibitor, pirtobrutinib, which recently got approved. How to sequence these drugs is still being evaluated.

The point is it’s important to know what had for frontline therapy, whether their genetics changed, if they have any new comorbidity, what their response was, and if they had any major side effects. All of those play a role in determining second and third-line therapy.

The Role of Genetics in CLL

Michele: Dr. Farber, this is something that CLL patients are always asking. I had my test when I was first diagnosed and this is what it showed, but now they’re showing something else. What happens to our genetics? Is it from treatment?

Dr. Farber: Yes, genetics can change. If you look at newly diagnosed patients who’ve never been treated, perhaps 5% or 7% will have a TP53 mutation or 17p deletion whereas if you look at populations of patients who were very heavily treated, particularly with chemotherapy drugs, up to 50% of those patients will have the dreaded TP53 mutation or 17p deletion.

If a patient needs a new line of treatment or is having progressive disease, if they haven’t had genetic testing, they should be checked

Dr. Charles Farber

By treating, you do one of several things. You can introduce new mutations or at least select a population of cells that have that mutation. What’s very important is if a patient needs a new line of treatment or is having progressive disease, if they haven’t had genetic testing, they should be checked again because there may be something emerging that was not there or not recognized earlier. There are a variety of different assays used, like FISH and next-generation sequencing.

It’s not the same biology through the course of the disease in a given patient. It can sincerely change in part through treatment and that’s one of the reasons in general that we tend to try not to treat patients until they need treatment. The International Workshop on Chronic Lymphocytic Leukemia (iwCLL) has criteria for who needs treatment and not everyone needs treatment.

They say there’s no benefit to treating early. I would take it a step further. There may be a detriment to treating a patient before they need treatment. It’s like shooting off your ammunition before the war begins. Some are seldom accused of starting treatment before an individual needs treatment. If a patient hasn’t had a genetic profile of their disease done in recent times and they progress, they should be checked out again.

Key Takeaways

Michele: What is your advice to patients? How can they most effectively advocate for themselves and have shared treatment decision-making conversations with their doctors, especially when they’re so overwhelmed with the amount of information they’re getting? How can they advocate for themselves when their doctor is not looking at newer therapies, like if they’re in a rural community and don’t have that advantage?

Dr. Farber: The patient needs to bring their spouse, a relative, or a loved one to review what the doctor’s saying at one of these critical junctures. It’s important to write things down.

When all is said and done, the patient can come up with a little chart where they can see the pros and cons of a treatment. You might have one for each different treatment being offered to you. Listen carefully to the doctor.

Come up with very focused questions. Write things down before you go in rather than having a free-for-all discussion.

Dr. Charles Farber

Ask their opinion. What do you think? Do you think one is better than the other? Do you think they’re equivalent? What aspects of one treatment would be better than another treatment? What aspects would be inferior? Are there any nuances to my current medical state that might make one treatment better than another? Come up with very focused questions.

Write things down before you go in rather than having a free-for-all discussion. Back in the day, we didn’t have options. There was one best treatment and we could change the dosing and the schedule to try and finesse it, but now we have different options. We have different agents within a given class. The doctor and the patient must come up with a good plan for the individual.

Dr. Lamanna: It’s often good for patients to bring somebody to their appointments because it’s hard to hear everything with one set of ears. Sometimes what the patient might be focusing on is different from what their loved one or friend might be. They may hear other aspects of the conversation.

The beauty of CLL compared to other cancers is we can have multiple conversations when we’re gearing somebody up for treatment. I often encourage them to write down questions and bring them to their next visit or message us. Thankfully, we have the leeway and flexibility of doing this at multiple sessions to try to answer their questions more thoroughly. That’s very rare. That’s not to say it never happens in CLL because sometimes it happens, but often, you have that luxury of time.

Thankfully, we have the leeway and flexibility of doing this at multiple sessions to try to answer their questions more thoroughly.

Dr. Nicole Lamanna

We also try to set up educational visits to go over the drugs and their side effects. There are a lot of good support groups for CLL where they can go over questions. I hook patients up early when I first meet them. I give them a book from The LLS talking about CLL and then I give them websites that they can visit. I say to patients that not everybody’s ready to go online and look at their disease. Dr. Google can be a problem, but for those who want to, I want them to go to reputable sites that talk about the disease.

Conclusion

Michele: This has been wonderful. I’ve learned so much from you. Thank you, doctors, for your devotion and dedication to helping CLL and SLL patients. We all better understand shared treatment decision-making and how important it is in our journeys.

Stephanie: Thank you so much, Michele. Thank you to Dr. Lamanna and Dr. Farber for all the work that you are doing with your patients and patients everywhere in CLL and SLL. It’s so important to be empowered again, especially in the space of this disease, which requires a lot of engagement and understanding because there’s so much rapid development happening with different therapies.

We want to thank our partners, The Leukemia & Lymphoma Society and The CLL Support Group.

I hope that you learned something from the program, that it spurred some thoughts, and that you can walk away with some actionable items on your list of things to do. We hope to see you at a future program. Take good care.

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Special thanks The Leukemia & Lymphoma Society and The CLL Support Group for their partnership.

We want to thank The Leukemia & Lymphoma Society for its partnership. The LLS offers incredible free resources, like their Information Specialists who provide one-on-one support in different areas for blood cancer. We also want to thank The CLL Support Group on Facebook led by our friends, including our moderator Jeff Folloder. They provide virtual support anytime for folks dealing with a CLL diagnosis.

We want to thank our sponsors for their support, which helps us to host more of these programs for free to our audience. The Patient Story retains full editorial control over all the content. While we hope this will be very helpful and that you walk away with a better understanding of this topic, this is not meant to be a substitute for your own medical advice.

Now we get to the great discussion ahead and I’ll send it to Jeff.

I like the long-term relationships you can have with patients and the variety of experiences with CLL. You have people who are quite ill, who have experienced a lot of treatment, may have had CLL that’s become resistant to some of those treatments, and need to do a lot of things to manage the CLL. You also see people who are living with it who currently do not have symptoms or do not need treatment.

I also like the fact that there are some people you encourage to do what they want with their lives and not focus on having cancer. Mostly, I’d like all my patients to be bothered by CLL as little as possible, but you do get people in a variety of situations and I appreciate that about working in CLL.

Everyone reacts completely differently to the treatments. For most patients, treatment side effects are common and can be impactful. Some of them are temporary, but some of them are more severe.

Impact of Recent Treatment Advancements on Side Effects

Jeff: I participated in a clinical trial where I received intravenous monoclonal antibodies. Like everyone who participates in a clinical trial, I received a stack of informed consent papers that looked to be about a foot and a half thick and described every single side effect that might happen with the administration of that drug.

The first time that I went to get the infusion, I was told to expect that it was going to take four to six hours. Unfortunately, it took 23 1/2 hours for me because I experienced pretty much every single one of its side effects. We got through them all. When the side effects happened, they were treated and we’d hit the reset button and start over again. As I progressed through the clinical trial, the side effects were minimized.

We’re in a different world now. Everyone reacts completely differently to the treatments. For most patients, treatment side effects are common and can be impactful. Some of them are temporary, but some of them are more severe. Sometimes treatment or even hospitalization is required. And then some people, for whatever reason, never have a single side effect.

Dr. Davids, the treatment landscape for CLL patients has truly evolved in the past couple of years. Could you discuss these advancements and how the side effects of CLL therapy, more specifically the BTK inhibitors, have changed over time?

Dr. Davids: To contrast with the older chemotherapy-based approaches, I told patients, “We’re going to start treatment. You’re going to need to take probably 6 to 12 months off from work and go on disability. Your whole life is going to change over this timeframe, but eventually, you’ll get better and get back to what you’re doing.”

When BTK inhibitors like ibrutinib first entered into trials, we quickly realized that these drugs are much better tolerated than the older chemotherapy-based regimens. There may be some side effects that arise, but we’ll deal with them. We’ll use various supportive care measures. We may need to reduce the dose, but you should be able to keep doing the things you want to be doing. You can usually keep working while on treatment.

We have venetoclax, which we usually give in a time-limited fashion for one or two years, and it has a different side effect profile than the BTK inhibitors. The nice thing about that is with a time-limited treatment, when we stop the treatment, usually the side effects go away or are minimized at least. There are lots of different options.

Jeff: When we first started treating CLL, the treatments were pretty drastic and the side effects were pretty intense for the majority of people. Now, with the new treatments, specifically the BTK inhibitors and drugs like venetoclax, the side effects aren’t as intense and are usually easier to treat. Is that a fair statement?

Dr. Davids: Yeah, that’s a fair statement. There are rare situations where you can have more severe side effects, but for the most part, most of our patients are doing very well with these new targeted therapies.

Relationship Between Side Effects and Quality of Life for CLL Patients

Jeff: For me as a patient, quality of life is at the top of my list. If I can’t do the things that I want, we’re going to have a conversation and figure out how to get there. Quality of life is a complex and personal concept, but it’s directly intertwined with cancer treatment side effects. Dr. Rogers, how do you define the quality of life for a CLL patient and how do the side effects of treatment impact this in your experience?

Understanding what matters most to the patient or what’s going to have the least impact on their enjoyment of their life is what we do.

Dr. Rogers: If we’re trying to decide between two targeted agents that are both good options with different side effects, understanding what matters most to the patient or what’s going to have the least impact on their enjoyment of their life is what we do and it can be different for different people.

With a BTK inhibitor, some of the common side effects are bleeding, bruising, joint pains, and abnormal heart rhythms like atrial fibrillation. I have a few patients where atrial fibrillation has been much harder for them than the CLL was at any point. If you’ve had someone who’s experienced atrial fibrillation before and it was bothersome to them, they’re going to try to avoid that treatment.

Treatment Side Effects vs. Treatment Schedule

Dr. Rogers: Meanwhile, for venetoclax, quality of life isn’t treatment side effects but also treatment schedule. When given as a first treatment, venetoclax is given for a year with obinutuzumab, which is a monoclonal antibody, and that requires an eight-week start-up. It was very striking what Dr. Davids said that we try hard now to make it clear to patients that we don’t want them to be disabled by the treatment they’re going through, even temporarily.

We mostly want you to be able to live your life and do what you want.

People have told me they worry about their lives being over and not being able to do anything when they do treatment. I usually tell them that some people get severe side effects that have to be dealt with, but we mostly want you to be able to live your life and do what you want. That’s how I define quality of life as a physician. I want my patients to be living their lives and doing the things they enjoy with minimal impact from their treatment.

These days, one of the biggest impacts can be the treatment schedule. You can continue to work or play golf, but you still have to come for visits and that’s the biggest thing that changes with treatment. The venetoclax and obinutuzumab regimen requires an eight-week start-up, which can be intense. I’ve had patients who choose not to do that because they don’t want to take time off work to go to infusion visits.

I’ve also had patients take online meetings during infusion visits, which I’m fine with as long as they’re still engaged in their medical care. I don’t tell anyone they have to work during treatment but some people love their job and don’t want to step away from it.

Quality of life is defined by the person and I try to minimize the impact of what we’re doing for CLL on people’s enjoyment of their life, whatever that is. Something that isn’t talked about a lot is trying to minimize the psychological impact of starting treatment. We make sure people know that treatment doesn’t mean that they won’t get to do the things they like, even though scheduling is something they’re going to have to deal with for the most part.

Dr. Davids: If they do want to do the venetoclax-based regimen, it’s a bit disruptive to their schedule. When patients aren’t on a clinical trial, I try to have some flexibility so that if they have an important event, we can delay by a day or two, but I try to keep them on schedule. It can be a little more challenging when patients are on a clinical trial because we need to rigorously adhere to a specific schedule.

For some patients, it doesn’t make sense to invest eight weeks or so in coming in for frequent visits. A lot of our patients are used to being seen every three to six months. If we tell them to come in once or twice a week for a couple of months, that can be challenging. Some of our older patients don’t drive anymore and need to get rides or live far from the center.

One of the beauties of the CLL treatment setting right now is that we have other options. Patients like that can go on BTK inhibitors. They require minimal monitoring and for some patients, that’s nice for their quality of life. They come in a couple of times early on to make sure everything’s going well and they can get back to their three- to six-month interval schedule.

Having different options for different patients is great. We’re on the precipice of having a new regimen approved in the US, which is a combination of acalabrutinib, one of the BTK inhibitors, with venetoclax. That’s going to be a nice advance because it will offer the opportunity for an all-oral, time-limited regimen.

One of the beauties of the CLL treatment setting right now is that we have other options… Having different options for different patients is great.

Right now, if you want all-oral therapy, you have to go with a BTK inhibitor and take it long-term for many years or you can go with obinutuzumab and venetoclax and have that opportunity for the one-year, time-limited therapy.

If approved, which we think it likely will be, acalabrutinib with venetoclax will be two pills. It’s a time-limited treatment of about 14 months or so and then you’re done. You don’t need to go through obinutuzumab infusions and that’s going to be a nice option to have for patients as well.

Dealing with Side Effects

Jeff: Whether you’re being treated, waiting for treatment, relapsed, or in remission, all CLL patients are dealing with some kind of symptom. It’s a fact of life, whether we call it fatigue, low platelets that make people bleed easily, joint pain, or AFib. Dr. Davids, what kind of practical advice do you give patients for dealing with those symptoms?

Dr. Davids: The disease itself can cause a lot of symptoms. There’s an interesting study where they took CLL patients who didn’t need treatment and randomized them to an early intervention approach with ibrutinib versus a placebo. It’s a rare opportunity in CLL to see what happens in a population being treated with a placebo.

As they stay on therapy longer and the CLL gets into a better remission, they tend to start to feel better overall.

In that study, there was a 90% rate of side effects in the patients on ibrutinib and a 90% rate of side effects in the patients on placebo. It was the same in both arms. That speaks to how the disease itself can cause a lot of issues, like fatigue, unintentional weight loss, sweats, and joint aches.

I counsel my patients that as they stay on therapy longer and the CLL gets into a better remission, they tend to start to feel better overall. They’ll develop better energy, their appetite may come back, they may gain some weight back if they’ve lost weight, and sweats can go away.

One of the more challenging periods is getting started on treatment because that’s when you have some side effects from the drugs and there’s still a lot of CLL around, so they may not be feeling great. As they get a few months into treatment, the CLL starts to get better. It involves counseling and coaching them through that. Hold out and be optimistic. It’s going to get better with time. For most patients, they may start feeling better pretty quickly, even within a few weeks of starting on therapy, because of disease control.

We have a very good multidisciplinary team. We have a great nurse practitioner who’s seeing the patients often more frequently than I do. We have pharmacists who help and look for issues with the drugs and side effects. The caregivers for the patient are a key part as well. It’s a team effort, but we do a pretty good job of getting patients through that more difficult period and to a better place where they’re feeling better.

How Can Patients Actively Participate in Their Care?

Jeff: Dr. Rogers, it’s hard for a doctor and the care team to know how to guide a patient through their side effects if they don’t know they exist. How do we do this? What does a patient have to do to get the best possible side-effect care from you and your team?

Dr. Rogers: One thing Dr. Davids said that’s important is I’m not the only person. Different members of the team are asking about side effects. Nurses, nurse practitioners, and physician assistants help too.

The nurse practitioner I primarily work with is a man and sometimes, patients tell him things that they won’t tell me or vice-versa. Sometimes the gender of the care provider or the care team member can make a difference in people disclosing side effects.

Asking about specific side effects that we know are common can help because I find people disclose more. If there’s one that they perceive is ruining their quality of life, we ask about it so we can get the spectrum.

Sometimes there are side effects that are bothersome to one person that aren’t to somebody else, like joint pain. We ask about it, learn about it, and suggest pain medication. But if the person’s happier living with it than trying any sort of intervention, I’m okay with that.

Effective Patient-Physician Communication

Jeff: Dr. Davids, it sounds like in the current landscape, most side effects are fairly easily managed for CLL patients. Let’s talk about how you deal with these side effects.

Dr. Davids: Every drug is different. Every side effect is different. Every patient is different. Sometimes we see more significant side effects with BTK inhibitors where we run into issues with bleeding and that can be serious.

Being very proactive and communicating with your doctor about what’s going on is important.

One thing that’s very important for patients on BTK inhibitors is to know that if they need any kind of surgical procedure, they need to stop taking their BTK inhibitor before and after the procedure. It’s helpful for patients to check in with us because every procedure is different and may require a different length of hold.

I have seen some patients run into issues where they forgot to call and ask us. They were taking their BTK inhibitor and had pretty serious bleeding issues after surgery. It’s about communication and anticipation. We’ve had situations where we’ve had to postpone surgeries. Being very proactive and communicating with your doctor about what’s going on is important.

Another common one that I see with venetoclax and BTK inhibitors is diarrhea or loose stools when patients are first getting started on these drugs. There’s a period when your body needs to adapt to the drug.

If it’s pretty significant diarrhea, we usually want to do some testing first before we do interventions. We’ll look for certain infections, like C. diff, which can be a more serious infection. It’s usually not there, but we like to make sure that’s not there before we recommend things like loperamide, which slows down the bowels.

There are little tricks as well. Sometimes taking the pill at a different time of day or with a different type of food can be helpful. With venetoclax, I’ve had luck with patients taking it with a fatty meal at night and when they wake up, they feel better and not having diarrhea during the day.

Sometimes we need to reduce the dose of the drug. I do find that it settles within the first couple of months. Most patients can then back off on loperamide and get back up to the full dose of venetoclax.

Overcoming the Fear of Dose Reduction

Jeff: Dr. Rogers, for whatever reason, a lot of patients are uncertain and fearful regarding dose reduction because it introduces a cloud of uncertainty to what’s going on.

Dr. Rogers: This is true across other cancers as well. People worry about dose reduction largely because they worry that the treatment will stop being effective if the dose is reduced.

With venetoclax, for example, the target dose for most people who don’t have drug interactions with it is 400 mg a day. However, when people have been on it for a while, there’s an efficacy at 300 mg or even 200 mg. If you’re taking 100 mg twice a week, you start to worry that it’s not going to work. There’s a point where you get to a dose where most people think that’s not going to be effective or with BTK inhibitors, you’re not going to have occupancy or the inhibitory action.

There’s a lot of room for dose reduction before you get to a point where the drug isn’t going to work. For people with side effects, maybe the target dose isn’t the right dose for them. When we do studies to design dosing of drugs, they look at drug levels in the blood, biological outcomes, and how much of that BTK protein is occupied with different dosing schedules. But that’s in a group of people and individuals can have different experiences.

There’s a lot of room for dose reduction before you get to a point where the drug isn’t going to work.

There’s some thought and some data to support this that people with side effects might naturally have different drug metabolism and maybe what’s needed is a different dose. With BTK inhibitors, there’s some scientific evidence that early in the disease, the drug is cleared by the amount of BTK in the body, which is a lot when there’s a lot of CLL, and further in is not a lot and the protein production is downregulated.

It’s quite possible that a lower dose is necessary to maintain that response after beginning treatment. Some of these side effects improve over time. People have a lot of CLL in their bodies. They see things improve every time they come for a visit. But a year in, when you’re looking at joint pain that’s interfering with your pickleball game when your blood counts look good, maybe it’s time to think about dose reduction. It’s also a time when the CLL is in a different spot and dose reduction might be more reasonable.

It’s quite possible that a lower dose is necessary to maintain that response after beginning treatment.

There are even some studies looking at databases of people using these drugs through insurance claims showing that reducing the dose did not result in a sooner time being prescribed a new treatment. It looked like it might even be going better for people probably because they were able to tolerate and stay on this drug.

It’s always worth asking your physician anything you’re worried about. If dose reduction is suggested, talk to them about whether they expect this will change your treatment outcome, but there are plenty of reasons to think that in most cases it will not. There’s a lot of room for dose reduction in a way that we know is not going to compromise how well the treatment works.

Fostering Effective Provider Communication

Jeff: We’ve talked about side effects. We’ve talked about the difference between male and female patients and how they communicate these side effects to their care team. Is there a way that you prefer patients to communicate with you?

Dr. Davids: I encourage patients to make a list of their issues ahead of time before coming to the visit. When you get to a visit, sometimes you’re like a deer caught in the headlights. Sometimes people don’t think of the things that have been occurring to them.

Keep a little notebook over the months in between the visits and jot stuff down. I find it most efficient to go through all those things in person together with the patient and counsel them through each one. I don’t mind if it’s a long visit.

A challenging mechanism that has developed is using a patient gateway to communicate, which has its pros and cons. It’s good for patients to be able to access their care team. But sometimes, over three months, patients send a message every time they think of a question, so they may be sending 15 to 20 messages in between their three-month visits.

It takes a lot of time on our end. We try to be as responsive as we can. We’ve hired additional staff to manage the volume of messages that come in because as you can imagine, if you have 10 or 15 messages from 200 or 300 of your patients, that’s a lot. I’m not saying that’s a bad thing, but we need to rethink  how we do that.

If patients are having more acute side effects, I encourage them to page us directly. We’re available to call back and have teams to help support us as well. If you’re sitting on a more serious side effect, that’s not good. Communication is key, but be smart about how to communicate.

A challenging mechanism that has developed is using a patient gateway to communicate, which has its pros and cons.

Dr. Rogers: If there are things you want to discuss, make a list. I’ve had a couple of people who send a list of questions a week before their appointment through the patient portal. We have a list now so that they know what it is and I can read what it is. Some people take physical notes, some people have them on their phones. If there’s something that they want to discuss, decide ahead and use your visit time to do it.

The patient portal is an excellent communication tool, but you can’t be doing that every day, asking something new. We do those during business hours. I tell my patients that they’re welcome to write a note at 2 a.m., but we will not be replying until the next business day. Sometimes, you get people who send a bunch of concerns and I tell them that we can’t answer all of these on the phone and that we’re going to schedule a visit. Occasionally, we’ll provide education. This is a concern. This is something that should be handled by the phone, so we can call and get it sorted out.

I have some patients who don’t use MyChart and they have a different way to communicate with us. It’s good to have multiple approaches. In terms of making lists of questions and sending them ahead, whatever helps you stay organized so that you get the answers you need.

Something that has been very helpful for us is open notes. We have been required to provide all test results to patients and provide notes. Some people like reading them but some people don’t. Some patients couldn’t remember something I said so they went back and looked at what I wrote and that helped. They didn’t have to call because they saw my notes. Some people know how to look at those. Some people don’t. They’re not written in patient-friendly language.

Patients will get their blood test results before they even come to see me, so they can think of questions about their results and I can address that during the visit.

Think through if you want to open your test results on a weekend and do what’s right for you.

Overall, it’s good to allow people access to their health information immediately. But I’ve had a few patients who call us up very angry that we released imaging results on a weekend. We didn’t do that; radiology did. Then they thought they had no way to reach out to us about something they were terrified about, which is also not true.

We have a 24-hour answering service if people are extremely worried about a test result that was released to them by the system on a weekend. Understand the process and the value in it but also think through if you want to open your test results on a weekend and do what’s right for you.

Dr. Davids: I feel very similarly about test results. It’s great to have access to all your data, but you have to know yourself. If you’re the type of person who’s going to freak out if you see something strange in a report and it’s a Friday evening and no one’s going to be able to get back to you for a few days, don’t open the report.

I see our job as looking at those reports, filtering out the things that aren’t worrisome, and telling you what’s important. Patients will be very worried about a tiny little lung nodule that wasn’t described before. If it’s 2 mm, I’ll say that they don’t have to worry about it, but if you see that result first and I’m not immediately available, you may be worried for days. It doesn’t bother some people and if you’re one of them, look right away. You have to know yourself and what you’re comfortable with.

If you’re the type of person who’s going to freak out if you see something strange in a report… don’t open the report.

Dr. Rogers: We have a system where if it’s a result that needs emergent action, which rarely happens in my clinic, the radiologist will call me so I can contact the patient. We don’t release test results with emergent findings without anyone on the healthcare team being notified, which I think some people don’t know.

Jeff: For the past couple of years, as I sat in the waiting room after having my blood work done, I have a very distinctive alert from my phone as my test results start coming in. I’m one of those people who are face down on the phone almost instantly because I want to know what questions to ask my doctor when I go in to review those results.

I’m coming up on 15 years of living with CLL and I’ve learned that the most important thing is not one test result; it’s the trend of the test results and how things are going over time. Not everyone is there yet and this is part of how we communicate with our care providers. This is how we work with our team.

Clinical Trials in CLL

Jeff: We’ve been talking about BTK inhibitors and it seems like the drugs keep on coming, one after the other after the other. When I started, it was pretty much FCR (fludarabine, cyclophosphamide, and rituximab) or nothing.

Let’s talk about how we got here. We’ve been doing all this research. We have CLL patients participating in clinical trials. We have the data coming back. How do you anticipate these advancements and how they’re going to impact treatment decisions? Are people going to put off starting treatment because something new is right around the corner?

Dr. Davids: We wouldn’t have all these great new drugs if patients didn’t go on clinical trials. The patients who came before helped bring these drugs to the patients of today. Patients of today also should consider clinical trials because you can help to develop the next wave of drugs for the next wave of patients. Patients deserve a ton of credit for making all this possible.

We wouldn’t have all these great new drugs if patients didn’t go on clinical trials.

Ibrutinib was a huge advancement. When I heard about a new BTK inhibitor coming along, acalabrutinib, I was skeptical at first. We already have a great drug with ibrutinib. Why do we need a second BTK inhibitor? Acalabrutinib turned out to be as equally effective as ibrutinib but with fewer side effects. It was a big innovation that acalabrutinib came along.

Then zanubrutinib came along and I said the same thing. Why do we need another, more selective BTK inhibitor? It turned out that in one study, zanubrutinib is better than ibrutinib in terms of how well it controls the CLL and is better tolerated.

Pirtobrutinib works very differently from the three BTK inhibitors and it can work even after all three of those other drugs stop working, so that’s a big advance. I’ve been proven wrong at each step along the way.

It’s helpful to have four different BTK inhibitors. I’m trying not to make the same mistake with a new class of drugs called BTK degraders, which are in early-phase clinical trials. This is another way to target BTK and they’re showing some significant promise.

It’s possible and very likely that eventually, we’ll have at least a fifth BTK inhibitor approved for this disease. It’s not what we’d call me-too drugs where it’s the same drug with a different label. These are all different drugs. They all have pros and cons and there’s a role for each of them in the treatment of CLL. It’s exciting times and continues to be exciting for patients to have all these options continuing to evolve.

It takes some courage to try new combinations or schemes for giving them.

Dr. Rogers: I completely agree. The only reason that we have these drugs is because people were willing to participate in clinical trials. I also see people who are afraid of participating in a clinical trial for fear of getting a placebo. Some of the lack of understanding of what research participation is a barrier to people doing it. It takes a lot of courage to do something where we don’t have all the information about how this particular treatment scheme is going to work.

A study we have right now for people going through their first treatment is a combination of currently approved drugs. Mostly, when people hear what it is, they say, “Okay, neat. These are drugs that you’re talking about as a standard of care.” It takes some courage to try new combinations or schemes for giving them. I always try to remember to cover that people will not be getting a placebo because we don’t have that in any of our current CLL trials.

Someone said once that participating in a clinical trial is like getting tomorrow’s treatment today. For people who are worried or don’t want to take an investigational drug, I remind them that these currently approved drugs were drugs that people got as research participants before they were on the market. They were able to benefit from what is a highly effective therapy before it was commercially available. This can directly improve the type of treatment people are getting, even though there’s some element of unknown because it’s a research study and we’re trying to learn more about these drugs.

For anyone considering research participation, definitely asking what’s known about the drug, where it is in development, and what the goal of this study is can help people understand better. When people are excited about approved drugs, we were able to treat people with those same drugs before they were commercially available because they participated in research.

These currently approved drugs were drugs that people got as research participants before they were on the market.

I would never suggest a clinical trial that I didn’t think was going to be highly beneficial to the person who was going to take that treatment. We’ve talked about choices for taking a first targeted agent, but there are people who have had CLL that’s now become resistant to several targeted agents. That’s where drugs we have under investigation are much more likely to be effective for their CLL than drugs that are currently on the market and a huge reason for people to consider research participation. At that point, you’re going to get something that we know is very likely to be better than commercially available drugs.

Shared Decision-Making in Your Care

Jeff: What you were saying got me thinking about this process as a collaborative process. It used to be like it or not. The paradigm was a patient presented with an illness, they saw the doctor, the doctor did an evaluation, the doctor prescribed a course of treatment, and the patient took the treatment. Things have changed now.

We have a lot of options. There are four BTK inhibitors. There’s venetoclax. There are monoclonal antibodies. There’s no treatment. I would like to think that we’re moving closer to a collaborative environment where the care team does the decision matrix with the patient. Dr. Rogers, how do you foster that environment with the patient?

We’ll discuss the treatments and by the time we’re done talking, it’ll be clear what to do and we can decide together.

Dr. Rogers: I strive to make my clinic a collaborative environment. When the venetoclax and obinutuzumab regimen was approved, you have BTK inhibitors versus venetoclax and obinutuzumab. I had a lot of consultations with people considering their options for the first treatment and asking me what they should do. Until I get to know you, I can’t help you. I can’t tell you what to do.

Usually, I say, “Why don’t we talk? I have some questions for you. You probably have some questions for me. We’ll discuss the treatments and by the time we’re done talking, it’ll be clear what to do and we can decide together.” That’s the best approach.

Some people don’t want to get options. They’re very overwhelmed by the options, so they want a recommendation. After a discussion, they say, “I don’t want to think about this. Ask me what you need to know to make the best recommendation for me, but I don’t want options. I want you to tell me what I should do.”

I find it difficult to pick for someone. I have to ask enough questions so that I can make the recommendation for what I think will be best. I respect the fact that some people get overwhelmed by the choices, don’t want to have options, and want to be told what to do. That’s not the way I prefer to do things, but if that’s what the person who I’m taking care of wants, then I try to do that.

I try to narrow it down. Often, there will be 1 or 2 options that I would prefer for the patient.

Dr. Davids: I have a very similar approach, I would say. Some patients prefer to be told what to do and it’s important to ask what their preference is upfront about how they want to approach it.

Another scenario is completely leaving it up to the patient. Present the options as all being equal and let the patient choose. I tend not to do that so much either, so I try to narrow it down. Often, there will be 1 or 2 options that I would prefer for the patient.

Sometimes you get the dreaded question: what would you do if this was your sister or your mother? I would recommend to a patient anything that I would for a family member because I believe in it no matter who I’m recommending it for.

There are scenarios where we’ve gotten down to maybe two or three options and the patient will say, “I would lean more toward this one based on what you’ve told me, but these other choices are reasonable too, so think it over.” Ultimately, it’s the patient’s choice. I see my role as guiding them to that choice and sometimes it does help if I express what my thought is for a particular patient. A lot of patients find that helpful.

Final Takeaways

Jeff: If a brand new CLL patient comes into your clinic and you’ve got 60 seconds to give them one message, what do you tell them?

Dr. Rogers: I usually tell people that we expect them to live with this for a very long time. The goal is to help them live as well as possible and be the least bothered as possible by CLL.

Dr. Davids: Depending on their age, for patients diagnosed with CLL in their 70s and 80s, I always say to them that our goal is to have them live whatever their normal life expectancy would be otherwise. We have very effective treatments and it’s unlikely that CLL is going to shorten your lifespan.

For younger patients, I don’t feel as confident saying that yet because if you’re diagnosed with CLL in your 50s, we don’t know what happens with these targeted therapies 30 years from now. I tell those patients that we already have a lot of good treatments, but over the next few years, we expect even more good treatments to be developed. The longer you live with CLL, the longer you’re going to live with CLL because we’ll have more and more treatments available. I also try to be optimistic.

Jeff: I was diagnosed with CLL at 46 and I’m now 60. Currently, I’m knocking out between 40 and 55 miles every week speed walking. I’m eating well and drinking well. I’m being a good father and husband. I’m doing all the things that I would want to do if I didn’t have CLL. I’m living a good life. It’s my mission as a patient advocate to make sure that it is possible to live a very good life, even with a CLL diagnosis.

I take an active role in my care. I listen to my care team when they say I need to do this, this, and this. I do what I need to do to present my body to my care team in the best possible shape so that when it is time to treat, we get to pick the right treatment plan so that I can live my best life. That is literally what I want for every single patient and caregiver. You can live a very long, very good life with CLL.

Conclusion

Stephanie: Thank you so much, Jeff, for your guidance in the conversation and for your perspective. We always want to make sure that we are emphasizing what that patient and care partner voice is. It is critical obviously beyond the education here.

Thank you so much, Dr. Rogers and Dr. Davids, for not only being incredible as CLL specialists but also for providing so much more time and extra time to help the community beyond the people and the patients you see in the clinic.

We also want to say thanks again to our sponsors for their support of our independent patient program and special thanks also to our partners, The Leukemia & Lymphoma Society and The CLL Support Group.

Thank you so much for joining us. I hope that this was helpful in one way or another. We hope to see you in a future program. Take good care.

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Thank you to The Leukemia & Lymphoma Society and The CLL Support Group for their partnerships.