HCP Roundtable: Fine-Tuning CLL Dose Modification and Side Effect Management Strategies from Patient Empowerment Network on Vimeo.
What is the rationale and evidence behind dose optimization approaches in CLL treatment? What role does patient education play in recognizing and managing CLL treatment-related side effects? Dr. Andres Chang of Emory Healthcare and Dr. Daniel Ermann of Huntsman Cancer Institute discuss optimizing CLL care and the importance of empowering your CLL patients during their treatment journey.
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Dr. Nicole Rochester:
Welcome to this Empowering Providers to Empower Patients (EPEP) program. I’m your host, Dr. Nicole Rochester. EPEP is a Patient Empowerment Network program that serves as a secure space for health care providers to learn techniques for improving physician-patient communication and overcome practice barriers. In this CLL roundtable, we are exploring fine-tuning CLL dose modification and side effect management strategies.
As the chronic lymphocytic leukemia treatment landscape evolves, we’re going to talk about the rationale and evidence behind dose optimization approaches in CLL treatment for those who may need therapy. We’ll also discuss strategies for dose modifications to mitigate adverse events while maintaining treatment efficacy, as well as approaches that are transforming CLL side effect management.
It is my honor and privilege to be joined by Dr. Andres Chang, Instructor in the Department of Hematology and Medical Oncology at Emory University School of Medicine. Dr. Chang specializes in treating patients with hematological malignancies including leukemia and lymphoma. Thank you so much for joining us, Dr. Chang.
Dr. Andres Chang:
Thank you so much for having me.
Dr. Nicole Rochester:
It is also my pleasure to be joined by Dr. Daniel Ermann, Assistant Professor in the Division of Hematology and Hematologic Malignancies at the Huntsman Cancer Institute. Dr. Ermann specializes in the treatment of patients with chronic lymphocytic leukemia and other forms of Hodgkin’s and non-Hodgkin’s lymphoma, and he is passionate about working towards a cure. Thank you so much for joining us, Dr. Ermann.
Dr. Daniel Ermann:
Great to be here. Thank you so much for having me.
Dr. Nicole Rochester:
So let’s start the conversation with dose modification, and I’m going to start with you, Dr. Chang. As the treatment landscape evolves for CLL, for some patient populations that need therapy, what is the rationale and evidence behind both dose escalation and dose reduction?
Dr. Andres Chang:
Well, so I think that the question of whether to dose-escalate or dose-reduce really depends on the treatment we’re talking about. For new therapies like BCL-2 inhibitors such as venetoclax (Venclexta), we do dose escalation at the beginning of therapy to mitigate potential side effects such as tumor lysis syndrome, whereas in most of the other scenarios we will try to do dose reductions in order to mitigate adverse events.
In all of these patients and in all of these cases, we do take into account the patient’s comorbidities. In the case of venetoclax, for instance, we think of whether patients have kidney dysfunction, and in the case of BTK inhibitors whether they have concomitant heart disease, hypertension, whether they are on anticoagulation, and also we take into account what other medications they have, in particular whether they have medications that affect their cytochrome P450 system.
Dr. Nicole Rochester:
Awesome. Thank you so much, Dr. Chang. Is there anything specific that you think healthcare providers need to know with regard to dose escalation and dose reduction?
Dr. Andres Chang:
So dose escalation in terms of venetoclax initiation is, we already have a pretty well-established protocol that is on the label of the medication, and this is really mainly to mitigate the risk of tumor lysis syndrome. And in terms of dose reduction, I think it really depends again on which therapy we are talking about and also on which particular side effect we’re talking about. And so I really encourage all the providers to really inquire and look into what potential side effects the patient might have so that you can adequately address this, because each side effect can be addressed or should be addressed with a different kind of strategy.
Dr. Nicole Rochester:
Wonderful. Thank you, Dr. Chang. Dr. Ermann, I’m going to come to you. How do CLL healthcare providers better understand dosing, particularly with the emergence of novel CLL therapies?
Dr. Daniel Ermann:
Yeah. Thank you so much for the question. So I think nowadays, most of us in the CLL community, we’re really no longer using chemotherapy. We’re using, like Dr. Chang said, we’re sticking to these novel agents, BCL-2 inhibitors, BTK inhibitors in the frontline setting. All of these medications have been studied to the optimal dose in their respective trials. And for the most part, we start every patient, except for the venetoclax ramp-up, we start all patients at the optimal dose for what we think for them is the maximum tolerated dose in the studies, which is the dose seen in the FDA package inserts and the recommended starting dose.
So I think for most patients, generally we start at what dose that is recommended. And then the only time we really begin to dose-reduce is as Dr. Chang mentioned, if we’re seeing side effects or intolerance. So these are things that I always start looking at very early when I start patients on treatments. I check in with my patients within the first two weeks of them starting a BTK inhibitor. And then during the venetoclax ramp-up with BCL-2 inhibitors, I keep a very close eye on them.
So I think though these novel therapies are extremely effective at treating CLL, they do come with some toxicities. And it’s important to be aware of the toxicities, to keep an eye on the patients when you start them and know what the dose reductions are and how to effectively manage them.
Dr. Nicole Rochester:
Thank you, Dr. Ermann. And I just want to acknowledge and thank both of you for highlighting the importance of partnering with patients, particularly in an Empowering Providers to Empower Patients program. We understand that this is a partnership between the healthcare providers and the patients. And so I appreciate both of you really highlighting the importance of engaging with the patients and then making necessary adjustments.
So, Dr. Chang, can you speak to any unforeseen or outdated practice-related barriers that may actually hinder your work and that of your colleagues as it relates to understanding CLL dosing?
Dr. Andres Chang:
Yeah, even though most of us in the CLL community have already moved to these novel targeted therapies, we do occasionally still see patients are referred to our centers who have undergone frontline chemo-immunotherapy, which for the vast majority of the patients nowadays, there really shouldn’t be an indication for that sort of treatment anymore. And so I think one of the main limitations is that we are using or at least some providers are using frontline chemo-immunotherapy and by doing so, they negate the great benefits that these novel targeted therapies have, particularly again in frontline setting.
Other unforeseen or outdated practices might be related to how patients, how we optimally mitigate the tumor lysis risks. And also occasionally, we might see some referrals from community practice physicians with patients who have CLL, and they have recurrent cytopenias or persistent cytopenias while in therapy, and they attribute it to toxicity of the therapy. Where in reality, if you do a bone marrow biopsy, they might be having a lot in the bone marrow, and that might be the answer for this particular so-called toxicity, but in reality it’s actually disease progression.
Dr. Nicole Rochester:
Thank you, Dr. Chang. So, Dr. Ermann, based on what Dr. Chang just shared and some of these, sounds like maybe knowledge or practice gaps, what are some solutions? How can we begin to bridge these gaps so that patients are receiving the best of the best with regard to therapy?
Dr. Daniel Ermann:
So there’s a little bit of, I would say that there can be a little bit of delay in certain providers changing their practice to the current academic approach. I think that from what I’ve seen, the best way to manage it is when patients are seen in the community by providers, I personally have quite a good relationship with many community providers in the community setting. And I encourage those providers if they get a new patient diagnosed with CLL, to recommend a CLL consultation.
And I would advocate that the patients also look into their disease and see whether or not a CLL consultation with an expert in the field of lymphoma or CLL may be good for them. And in those ways I’ve seen, personally I co-manage many patients across the Western United States. They’re still able to be seen by their local oncologist and also be seen for consideration of clinical trials in the CLL space when indicated for their more rare disease.
So I do think it comes from both providers and patients, but I think empowering your patients, letting them know that there are other doctors who may specialize in a condition that they have is really important. And when patients do that, not only are they happy, their local oncologist is happy. It makes it kind of better for everyone.
Dr. Nicole Rochester:
Absolutely. Thank you, Dr. Ermann. I love that idea of a team-based approach. Thank you so much. Well, let’s move into talking about side effects. And you all have already alluded to the importance of dose modification with regard to side effects and minimizing toxicity. So I’m going to go to you, Dr. Ermann. What techniques do you use in your practice for optimizing treatment efficacy while minimizing toxicity? And feel free, if you’d like, to share a specific example.
Dr. Daniel Ermann:
Yeah. Great question. So in CLL, there are a lot of unique toxicities with our CLL-directed therapies. I’ll take, for example, BTK inhibitors. So BTK inhibitors have certain off-target effects. The way these medications work is they turn off BTK, and that’s like flipping a switch that decreases the growth of the CLL cells and eventually causes them to die. However, some of the unique toxicities we see are things like atrial fibrillation, bleeding, bruising, infections, to name a few.
So, for example, you would like to start a patient optimally on the maximum dose, which is the kind of recommended starting dose. However, let’s say a patient gets a side effect such as bleeding or atrial fibrillation, I usually will follow the package insert pretty closely. In most cases, the recommended management is to hold the drug until a side effect resolves and then resume at the same dose. In my practice, I found that with many of our novel therapies, there are some cases where you can continue the same dose, but oftentimes you’ll need to dose-reduce.
And I will say from my personal experience, I think dose reduction can make a big difference in the side effect profiles of these medications. I’ve seen reduced bleeding, for example, reduced rates of atrial fibrillation. With BCL-2 inhibitors, I’ve seen reduced rates of neutropenia, for example. And I’ll just say from my experience, I haven’t seen too much compromise in efficacy. So I think I would recommend for providers when you’re thinking about dose reduction, it’s really a balance of toxicity and efficacy. And I think with just how good our treatments are for CLL these days, I try to reduce toxicity. And I think in that way, it does maximize their efficacy.
Dr. Nicole Rochester:
Thank you, Dr. Ermann. What about you, Dr. Chang? How do you approach dose adjustments for CLL patients, particularly those who may be experiencing severe side effects? And what factors influence your decision-making process?
Dr. Andres Chang:
Yeah, so first of all, I agree with Dr. Ermann that I think trying to mitigate side effects and oftentimes following the package insert is really, really helpful. One of the things that I want to add, though, is I do spend quite a bit of time before starting any medication, educating patients and trying to teach them about what potential side effects, what to look for. And importantly, if there are mechanisms to mitigate or prevent those side effects, I will spend quite a bit of time talking about that. And these can be things such as taking caffeine to prevent an acalabrutinib-induced (Calquence) headaches, for example, maintaining adequate fluid intake and hydration to minimize the risk of tumor lysis, and so forth.
I find that by spending that time with patients ahead of starting therapy, that oftentimes it allows patients to identify the side effect and also start addressing it even before needing to come back to the clinic. My team, in addition to myself, also spends quite a bit of time, and we perform phone calls, follow-up phone calls, and things like that, that are conducted by my pharmacist or by my nurse. And together, I find that oftentimes just by talking through these potential issues, patients will feel a lot better.
Now, depending on how severe an adverse event is, or a side effect is, I tend to potentially dose-reduce somewhat quicker. Or if there’s an alternative, like in the case of BTK inhibitors, I will be a little bit more prone to switching from one BTK inhibitor to another, because there is data suggesting that if you don’t tolerate one BTK inhibitor, you can tolerate a second one.
And that’s particularly true if we are seeing some of these side effects that arise in the long term, particularly with ibrutinib (Imbruvica), and switching them to acalabrutinib or zanubrutinib (Brukinsa), oftentimes resolve those kinds of side effects. And I’ve seen that particularly true in cases where I see hypertension induced by ibrutinib (Imbruvica). I have a couple of patients where they are four or five years into ibrutinib therapy, came in with uncontrolled hypertension, I switched them to another BTK inhibitor, and the hypertension gets better controlled.
Dr. Nicole Rochester:
Thank you, Dr. Chang. I just really appreciate again how both of you are continuing to highlight the importance of a multidisciplinary team. So the importance of involving the patients, educating the patients, both ahead of time and as you’re beginning treatment. And also, you mentioned bringing in the pharmacists and bringing in your nurses and all of the other members of the support team. So I really, I really appreciate that. And speaking of patient education, Dr. Ermann, I’d love for you to share if you can have any ideas around the role that patient education plays in recognizing and managing treatment-related side effects.
Dr. Daniel Ermann:
Yeah, absolutely. So I’m a big advocate on educating patients, and I completely agree with what Dr. Chang mentioned. I think prevention is the key. I think the more work you can do up front to improve the outcomes down the road, the better. So in my experience, what I do for my patients in the clinic when it comes to education is I actually, I do quite a bit of, quite a few things. So I not only do I myself personally educate the patient on the drug, I also have my pharmacist meet with the patient either in person or over the phone depending on where things are at. I also print out handouts, because occasionally we hear a lot of things and as patients, sometimes it can be overwhelming, even as doctors, it can be overwhelming hearing a lot of things at once.
So I like to print things out for my patients, whether it be from UpToDate pages, whether it be from things like the websites that have drug information like Chemocare, etcetera etcetera. And I also utilize kind of these free sheets that you can find throughout…from many different organizations such as, like Lymphoma Research Foundation or others that have drug information, safety information.
And then I also recommend them easy ways to contact us, whether it be through like a messaging app or calling our office with questions. I think that educating your patients on what to expect with these drugs is really important. Fortunately in CLL, a lot of our medications, though there are some unique toxicities, are overwhelmingly much better tolerated than many other therapies for other cancers. So that is one good thing. So you want to give them enough information, but you don’t want to scare them to thinking that they’re going to have the worst of every situation, but I think it’s very important, especially up front, and then most patients will see how different drugs affect them.
Dr. Nicole Rochester:
Thank you, Dr. Ermann. I love that you’re offering multiple different ways, because like you said, some people may be auditory learners. Many of the patients, when they’re hearing this information for the first time, as you alluded to, they’re going to be overwhelmed. They’re not going to remember. So I love the idea of also leaving them with something in writing that they can refer to later. What about you, Dr. Chang? You’ve been doing this for a while now. Are there any specific strategies or something that works really well for you, a particular tactic as it relates to educating your patients about side effects?
Dr. Andres Chang:
Yeah, I couldn’t agree more with Dr. Ermann. I spend quite a bit of time, again, speaking directly to my patients, having my team speak to my patients, and I follow many of the similar strategies that Dr. Ermann has already mentioned. In particular, places like Leukemia & Lymphoma Society, Leukemia Lymphoma Research Foundation, the CLL Society, all those societies have a wealth of information about the different treatments and approaches that we normally use for CLL. And I find it very useful that as part of our discharge paperwork from clinic, we do include links to those societies so that they can find additional information.
And aside from that, I think once you have a good rapport with a patient and your team has a good rapport with a patient, as long as there’s good communication either through the patient portal, through phone calls, through return visits, I find that once patients are very well-educated, then they are actually very comfortable starting therapy and pretty much know exactly what to expect at each step in the therapy. Whether it is a dose escalation week for venetoclax, for example, or what happens when we have to hold a medication for a procedure, when to restart, and those sorts of things.
Dr. Nicole Rochester:
Wonderful. Thank you both. Well, we’ve talked about the importance of educating patients. We’re going to circle back to our healthcare providers. And, Dr. Chang, I’m going to stay with you for a moment. Can you share any successful strategies for healthcare provider to healthcare provider education, any innovative approaches with regard to side effect management in CLL?
Dr. Andres Chang:
Yeah, I think that as important as educating patients, educating other healthcare providers is as critical. And as such, I think one of the missions that we have at academic institutions is that we should also offer some educational aspect to our consultant physicians across the community or nurse practitioners or nursing staff.
And so one of the things that I commonly do is that my notes tend to have a couple of paragraphs that explain my rationale behind the recommendations with sources, primary sources of information if they want to look up any particular data where I’m basing my decision on. And that happens both in terms of picking this treatment versus this other treatment, what is the efficacy data, but also for side effect and adverse events data.
I also, as part of the Winship Cancer Institute, we have a big outreach program to our community. And I’m sure Dr. Ermann has [this] too over at Utah, where we have outreach programs and reach out to other community oncologists, trying to give them information about the newest and latest therapies. We do symposia. And we also have an app where community oncologists can actually look us up directly and give us a call or something that, in case they run into problems.
And then we are happy to talk to them and help guide the management of their particular patients. I find that this kind of verbal communication and live direct provider-to-provider contact has been very useful. And I think that the community oncologists have really appreciated that.
Dr. Nicole Rochester:
I’m sure that they do. That is amazing. That’s awesome. What about you, Dr. Ermann? Do you have anything to add in terms of what you all are doing at your institution to communicate with other healthcare providers?
Dr. Daniel Ermann:
I just have to say Dr. Chang and I were on the same page. I completely agree with everything he said. I think that he is…it’s we’re super imposable at this point. I do the exact same things as he does, which is great, I think. I think that that’s fantastic. A couple other things I would just say as well is that I agree 100 percent. Communication is the biggest thing. Communication is not only one of the most important things, but it also can be a big barrier. So I think fostering communication between, a lot of what I do is deal with local oncologists as the academics. So I may only see patients a couple times a year, whereas the local oncologist may see them a couple times a month.
And so having an open line of communication, whether it be cell phone, like occasionally I’ll be texting local providers, calling them, having their phone number is very helpful, emailing back and forth. And then after I see patients, similar to Dr. Chang, I document well in my notes. And I also have my team send the note to them through fax or other means. So things like that, I think are very valuable and important and I think are game-changers when it comes to excellent patient care, because the communication barrier can sometimes be one of the biggest ones.
Dr. Nicole Rochester:
Absolutely. Thank you for that. Before we wrap up, we know that social media is often leveraged in healthcare among providers. And I think you mentioned, Dr. Chang, an app. So are there any other digital tools or are there ways that either of you leverage social media in order to manage side effects, either with education to providers or to patients? And, Dr. Ermann, I’ll start with you on this one.
Dr. Daniel Ermann:
Sure. So social media is a tricky one, because not everyone uses it. Also in CLL in particular, our median patient age is around 70 years of age, and not too many of my 70-year-old patients are on, but they can be. So I think as a provider, there are a couple of things. I’ll be honest, Twitter is actually, can be a great resource. If you follow certain providers in the field, you’ll get some updated information before anyone else, including especially during our annual ASH meeting, there’s an ASH app. And if you could attend the meeting, you’ll see that most updated data. And you can see that on Twitter and/or X as well. Other than that, we also have a Huntsman app similar to Emory. But I think that that’s about as far as social media goes for me. What about you, Dr. Chang?
Dr. Andres Chang:
I agree with Dr. Ermann that places like X and LinkedIn, if you follow the right people, you can get very useful information. And I think that that’s particularly true for people within the academic community and healthcare providers. But for patients per se, I think that this could be a little bit more tricky. And so I try to steer them away from that, in fact, and I try to kind of keep them within the main resources.
And if they have any questions or they have…or they’re confused about something, I always tell them, feel free to send me a message, and we’re happy to discuss whatever you read. And so I find that patients really appreciate the openness of discussing data because sometimes the data might be not very accurate. And by having that trust, they find it comfortable talking about things that might not be as conventional as we might think so.
Dr. Nicole Rochester:
Wonderful. Fully understood. There are certainly some risks associated with getting information from social media. So I appreciate you all providing that balance. Well, it’s time to wrap up our roundtable. And, as always, this has been an incredibly enlightening conversation. So as we close, I’d love to get closing thoughts from each of you. And I’ll start with you, Dr. Chang. What is the most important takeaway that you want to leave with those healthcare providers who are listening and watching this program?
Dr. Andres Chang:
Yeah, I think that the most important takeaways are actually two things, I think. One is really, really important to educate patients about their disease, about their treatment, about the potential side effects, and also to try to anticipate and mitigate those potential side effects so that patients know exactly what they’re expecting.
And then the second thing is really essential to have a great team around you because practicing medicine, particularly oncology, is not a solo practice. We really need a village to take care of our patients. And so having well-trained nurses, having excellent clinical pharmacists, all of them are essential members of the team that will help with patient care.
Dr. Nicole Rochester:
Wonderful, Dr. Chang. Thank you. And, Dr. Ermann, what are some closing thoughts you’d like to leave with our audience today?
Dr. Daniel Ermann:
I would say is that I would say don’t be afraid. In medicine, there’s often this thought that reducing treatment doses or things like that is a bad thing and you shouldn’t do it. I would say I would empower providers to not be afraid to dose-reduce, especially to mitigate very undesirable toxicities. So I’d say don’t be afraid to dose-reduce. There’s a lot of, at least in some of our medications, good efficacy data showing that dose reductions can have similar, if not the same, efficacy profile while mitigating toxicity. So I would say don’t be afraid to dose reduce, especially if the toxicities are not improving. Don’t be afraid to dose-hold.
And when it comes to empowering our patients more, I’m a big advocate on empowering patients. Particularly diseases like CLL, where two-thirds of patients at diagnosis don’t require treatment, and they’re told that they have cancer, and then all of a sudden they’re told that they don’t need treatment can be very scary. And I think that’s when patients feel like they have their disease understood and that they’re doing the best that they can for their own disease, it makes it better for everyone involved.
So I think empowering both providers and patients is kind of the optimal way to do things. And those are the best patients. When you deal with someone who knows their cancer, knows what’s going on, sometimes I get patients they know as much or more than me and I’m like, wow, this is incredible. Those are the best.
Dr. Nicole Rochester:
That is such a perfect way to end this program. An empowered patient is the best patient. Thank you so much, Dr. Chang. Thank you so much, Dr. Ermann, for this amazing discussion about managing side effects and managing dose modifications and educating patients and educating providers with regard to CLL. Thank you again for tuning in to this Empowering Providers to Empower Patients, Patient Empowerment Network Program. I’m Dr. Nicole Rochester. Have an amazing day.
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