From Worn Out to Energized: Tackling Fatigue after Transplant and CAR T-cell therapy

Transcript of Presentation:

(00:01): Steve Bauer: Introduction. Hello, and welcome to the workshop From Worn Out to Energized: Tackling Fatigue after Transplant and CAR T-cell Therapy. My name is Steve Bauer, and I will be your moderator for this workshop. It's my pleasure to introduce today's speaker, Dr. Alexandra Muench.

(00:21): Dr. Muench is a clinical health psychologist at the University of Pennsylvania Perelman School of Medicine. She specializes in the treatment of sleep disturbances and fatigue in individuals with cancer. She developed the Penn Sleep and Cancer Clinic, where she delivers tailored behavioral interventions designed to address the unique challenges faced by cancer patients and survivors. She's a passionate educator and advocate for patient-centered care. Please join me in welcoming Dr. Muench.

(01:01): Dr. Muench: Overview of Talk. Hi, thank you so much. I'm so excited to be here. I do want to make a small correction, I've recently transitioned from Perelman to Penn Medicine, Princeton. I'm still at Penn, but I'm now in their integrated clinic, where I work with oncologists in an integrated setting, helping folks with all kinds of things related to cancer, including fatigue and sleep issues. As just mentioned, we're going to talk about how we tackle fatigue.

(01:31): I like to start presentations like this by saying that we are still in the early stages of figuring out how we identify and treat cancer-related fatigue. The research is growing, but some is specific to transplanted CAR T-cell therapy, while some of the research has been done in other cancers, and we're working tirelessly to try to expand this and figure out the best way to go about treating fatigue, both during and after treatment.

(02:05): I do like to start with some background defining fatigue. What is fatigue? I'd like to start with the dictionary, with our old friend, Merriam-Webster here, which defines fatigue as "a weariness or exhaustion from labor, exertion, or stress." That's our very broad definition, but what we're going to see in a minute is that, in the context of cancer, cancer treatment, and cancer survivorship, fatigue is a little bit different.

(02:38): What, then, is cancer-related fatigue? The National Comprehensive Cancer Network, also known as the NCCN, defines cancer-related fatigue as "a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion, related to cancer treatment, that is not due to recent activity, and interferes with usual functioning." That's a really big mouthful, so let's break that down.

(03:08): Cancer-related fatigue is not proportional to recent activity and interferes with usual functioning. What is cancer-related fatigue? It's distressing, and it can be persistent. It can affect you physically, emotionally, or cognitively, and it can result in tiredness or exhaustion. It's not proportional to recent activity – this is a big one. If we go back to our Merriam-Webster definition, and we think about things like exercise, or if we've had a big day, that's often proportional to the activity and the energy we expended. But cancer-related fatigue is not, which makes it distinct. And it interferes with usual functioning. Probably the biggest thing is that it makes it hard for us to live our lives in a way that brings us joy and adds value. This is often what I'm seeing, when I'm talking to folks, is that their quality of life is greatly diminished.

(04:02): These are different beasts. Fatigue, as we know it broadly, is proportional to our activity. It can be from labor, exercise, exertion, or stress. But cancer-related fatigue is vastly different, a different beast. It's more severe, more upsetting, more disabling, more long-lasting, and much more difficult to relieve, which we'll talk about in a little bit.

(04:33): How is cancer-related fatigue, also known as CRF, experienced? There was a meta-study reviewing 16 qualitative studies in which they asked folks, "How do you experience your cancer-related fatigue?" And six overarching themes were identified: loss of self, embodied experience, small horizon, (mis)recognition, role changes, and finally, regaining one's footing.

(05:01): When I think of loss of self, or read about it in the literature, and when we talk to folks who are experiencing this, it's losing a sense of who they are.

(05:10): Coming back to role changes, if before having cancer-related fatigue, you were able to run five miles, and that was a big part of your day and your life, then not being able to do that can make you feel sad, which can increase stress, thus maintaining cancer-related fatigue.

(05:29): (Mis)recognition refers to not understanding what you can and can't do. When things change so quickly, you can feel like you should be able to do these things, but it's hard. Role changes come under this, too. We talked about that. Embodied experience involves having these physical changes. People describe this as their body feels heavy. And small horizon, being that your world starts to become small as you feel more limited.

(06:00): But there are ways to manage this where you start to feel like you're regaining your footing and you come to accept that, although you might have this symptom, you're able to still live a full life.

(06:15): CRF is reported by roughly half of cancer patients and is the most common side effect of cancer treatment. The big question everyone always asks is, "How common is cancer-related fatigue?" The short answer is it's very common. In one study, by Ma and colleagues, they found about 52% of patients across 84 studies reported having cancer-related fatigue at some point. It is the most common side effect of cancer treatment, and it can be a symptom of cancer itself, so when our body is sick, we start to feel fatigued. It's often rated as the most distressing. There was a paper specifically looking at CAR T-cell therapy, and in this study patients rated fatigue as the most common symptom and also the most long-lasting.

(07:04): Frequency of CRF varies with type of cancer, type of treatment, psychosocial stressors, and other comorbidities. One caveat here is that this research is up and coming. What you'll see, if you look at the literature, is that although Ma did a meta-analysis and looked at 84 studies, this 52% varies. It could be anywhere from 20% of patients experiencing this to 95%. And the reason for this is it really depends on the type of cancer, the type of treatment, sex or gender, other psychosocial stressors, and other comorbidities, both physical and mental. In the research that I'm doing, we’re trying to drill down on this to figure out, by type of cancer and by treatment, the risks of this symptom.

(07:57): Coming back to Ma's study, they looked at cancer-related fatigue in regard to severity, sex, age and treatment. What they found in their study was that most people rated their cancer-related fatigue moderately. By sex, it was females who seemed to experience a little bit more, 39% versus 34%. Folks over the age of 65 seem to experience fatigue a little bit more than folks under the age of 65. We are doing a study that's ongoing where we're collecting as much data as we can, looking at cancer-related fatigue across different diagnoses, age, sex, et cetera, and radiation treatment. And we found a similar thing, that folks over the age of 65 do seem to experience and report cancer-related fatigue more than the younger cohort.

(09:03): Chemotherapy and radiation produce more CRF than surgery alone. The type of treatment seems to matter, too. This is pretty consistent across the literature. Chemo and radiation, when compared to surgery alone, seem to produce more cancer-related fatigue. Again, this is ever-evolving and growing, and different types of treatments are coming on board, so we will keep evaluating.

(09:26): Why does cancer-related fatigue happen? It's like a needle in a haystack. There are so many things that can cause fatigue that we don't really know for sure. What we do know is there are some things that can contribute. Systemic inflammation, such as in CAR T-cell therapy, anemia, depression, sleep disturbance. We'll come back to sleep disturbance, because we do think that cancer impacts sleep, and subsequently it can cause daytime consequences like fatigue. Physical inactivity, higher body mass index, pain – if you have pain, that can certainly impact you, especially if it's impacting your sleep at night.

(10:09): Type of transplant seems to be related, i.e., the type of stem cell transplant you get. Infection, if you're having any respiratory issues, any problems with other organs. Coping strategies and expectations are things we talk about with medical teams as well. Depending on what the patient's needs are, it's probably helpful to be transparent about what could happen. It doesn't mean you're going to develop these symptoms like cancer-related fatigue. However, you can, and it's important to educate folks around what could happen. Cancer treatments, depending on the treatment you get, might make you more prone to developing cancer-related fatigue.

(10:56): CRF can begin happening even before diagnosis and sometimes prompts people to seek a diagnosis. When does cancer-related fatigue happen? The ultimate question. I think about it a lot. We suspect that it's probably happening even before diagnosis. This is an assumption that's hard to test because I can't go back in time, as much as I would like to. But anecdotally, a lot of folks will say to me, "I knew something was off because I just wasn't feeling like myself. I was feeling fatigued, so I went to the doctor." We suspect it probably happens at some point before diagnosis, then continues through treatment, and then oftentimes into remission. In CAR T-cell therapy, a lot of the studies only look out three months, but fatigue still seems to be present at that time. Overall, it does seem to remit, but more work needs to be done there to determine how long fatigue is lasting into survivorship.

(11:55): There are other cancers, like breast, where the fatigue is partially due to the post-treatment drugs that people are on, so it can last way longer. The jury is still out on that.

(12:10): Transplant and CAR T patients often experience CRF as the longest-lasting, most impactful, and most persistent symptom arising from cancer and treatment.  In terms of how long CRF lasts, there was a study done where they asked patients to rank each symptom as lasting the longest. And what they found was that 54%, more than half, reported fatigue as lasting the longest. They then asked what symptom impacted everyday life the most and fatigue, again, was rated as the most persistent symptom. Which, when I saw this, didn't shock me. It's often the one that people come in with, that and pain, as having the most impact and burden on their quality of life.

(13:00): Specific to CAR-T cell therapy, there was a study done by Whisenant and colleagues, in 2021, that looked at different symptoms that present with CAR-T cell therapy. They found that fatigue was, again, the one that was most prevalent. Pain was also up there, but fatigue seemed to be the one that was impacting quality of life the most and lasting a bit of time. Again, the study looked out about three months, and didn't follow up after that, so I'd be curious how folks are faring after that three-month point.

(13:45): The big question is what can be done about cancer-related fatigue. We don't at this time have a medication that can be given. I typically put together with my patients what I call the fatigue package, pulled from the literature, which includes things that you can do to take the edge off the fatigue and maybe roll it back a little bit. I use the analogy of pain. If you've ever had any type of pain, typically what's recommended is you take the medication before the pain gets really bad. Likewise, intervening on fatigue early (and sleep disturbance for that matter) can be prophylactic in nature so it doesn't get too serious. I'm always encouraging my medical providers, "Consult me at the first mention of fatigue, not when it's already having a detrimental effect on someone's quality of life."

(14:43): The first intervention in the fatigue package is patient and family education and counseling, because we don't want to forget the caregivers. Providing education about fatigue, especially if undergoing fatigue-inducing treatments like radiation, chemo, and CAR T-cell therapy. What is the risk of fatigue? How long might fatigue last? What can be done about it? In terms of expectations, "How am I going to feel after treatment? Are there ways to navigate this beforehand, for the caregivers as well? What can the caregivers expect for their loved one who is undergoing this?"

(15:23): We also want patients to recognize that fatigue is not necessarily a sign the treatment is not working, or that the disease is progressing. After chemotherapy, fatigue is the worst, but that doesn't mean that the treatment isn't working. Chemo can have an effect on your system that causes fatigue, and after a few days it can remit. Just recognizing what is a normal symptom of treatment, and what might not be, can be helpful.

(15:50): To reiterate, fatigue can be a consequence of treatment, and other things can also have an impact. You can seek nutrition consults if you're having trouble eating, which is totally fair, or trouble drinking water.  

(16:17): In terms of general strategies, energy conservation, also called activity pacing, is a big one, and I often struggle with how we measure this. Pain literature has done a good job of expanding on this. In chronic pain they talk about activity pacing because oftentimes fatigue is not like  having a "bad day" every day. It comes and it goes and, like I said earlier, it might be worse after treatment.

(16:49): I encourage my patients to engage in this activity pacing, which means learning to manage some expectations around what you can and you can't do. It might be you're used to running a few miles every day, and that might not be possible right now, but could you take a walk? It might not feel the same at first, we're all active people, but is walking helpful for now? Then maybe we can build up to running again, if that's possible. Think of your energy level as a flat line, not as a good day, where you go up. Maybe you don't feel good for a couple of days, good day, bad day. It's about starting to tune into what your body needs. Maybe today we need to relax, take a bit of a nap. It's starting to tune into, "What can I do right now? What's good for me? What feels good?" And maintaining energy levels, so you're not crashing and burning.

(17:56): There are apps for this which I sometimes recommend to my patients. No conflict of interest here, just something that I recommend, there's an app called the Visible app. It was created specifically for folks who have fatigue. It'll track your energy and say, "You know what? Maybe you need a rest. Maybe you can be a little bit more active today." Or you can maintain a diary where you say, "You know what? Yesterday I helped my kid move, and then I was out all day, and I felt really bad the day before, and I didn't take any breaks." And bring that to your doctor, or someone like me, and we can go through and say, "Okay, what could we have done differently to make sure you're able to maintain your energy, and not have a few days where you don't feel so good?"

(18:48): Distraction is another coping mechanism. When I think of distraction, it’s not in a negative way. Once we become really focused on the symptom, which is hard not to do, it can be all consuming, so try finding value: what are the things that maybe you've disengaged from in your life, that you could bring back in? It might look different, like walking versus running, but distraction can be a powerful thing.

(19:13): Napping can be another coping mechanism. Naps. On social media, in our culture and the zeitgeist, napping has been seen as a no-no. I don't feel that way, and the literature tends to agree, in the context of illness and treatment and things like CAR T-cell. What I try to do for my patients is to put some boundaries around that nap. For daytime naps, 30 minutes or less, in bed, because we want the bed to be paired with sleepiness. We don't want to spend all our time in bed, because that can lead to wakefulness in the bedroom. Nap before 3:00 PM.

(19:52): One thing that I love is something I heard from a military psychologist. It's called a ‘nappuccino.’ I wouldn't encourage inserting caffeine if you don't drink coffee but, if you drink coffee, have a small cup of coffee before you lay down for your nap. The reason is that you get a double whammy of rest. You get rest and restoration from the nap and, by the time you wake up 30 minutes later, you have the coffee hitting your bloodstream. That can help you feel a little better, if you feel you need it.

(20:26): Another caveat about napping, it doesn't always mean falling asleep. It could just be taking a moment, taking 30 minutes to yourself, if you have it, or even 15, 10, 5, to rest. Then come back to your day.

(20:47): Some psychostimulants may take the edge off fatigue. Let's talk about pharmacologic interventions, because this is a question I get asked a lot. We don't really have any that work super well. There's some evidence that psychostimulants like modafinil (Provigil), as well as corticosteroids, can take the edge off fatigue, and that's something to talk about with your doctor. There's some thought that the reason they don't work really well is that the fatigue we're experiencing is at brain level or neurobiological level, so the psychostimulants aren't hitting the parts of the brain they would need to to cause relief. But they can take the edge off, and I have seen doctors prescribe modafinil.  There's some literature to support it. In terms of the size of the effect, they're moderate. But it depends on you, and the treatment. Oftentimes, the coffee that I just recommended will have the same effect.

(21:43): There's a bit of hope potentially coming, in terms of medication. I know I'm a psychologist, but I'm also a believer that, especially in the context of acute treatment right after therapy, medications would do a world of good. And there are some medications that could potentially be on the market soon that might be helpful, so stay tuned for that.

(22:09): There are a number of non-pharmacologic interventions:  

We've talked a little bit about physical activity. This is a significant development. A lot of this has come from the multiple sclerosis literature, and I don't want to equate the two, because we don't really know if, across disease states, the fatigue is similar or different, especially mechanistically speaking. However, there is some literature to suggest that, even in cancer, physical activity can be helpful. We'll talk more about that in some detail.  

Psychosocial intervention, like coming to talk to someone like me, so we can dive deeper in on your fatigue and anything that might be causing it.  

Bright light therapy. Another really good one, especially if you live in a place that's dark for a few months out of the year, I highly recommend. We'll go more into that in a moment.

(23:00): Any type of exercise can help with CRF. Physical activity. There was a study done, a meta-analysis, which looked at 72 studies across over 5,000 patients in active treatment or follow-up. They showed that exercise had a moderate effect, which means probably around 0.5, of reducing cancer-related fatigue compared to control group. This is important. Exercise type does not matter, and the more tailored the better. Even a little bit helps. If you're really feeling fatigued, can you get up and just walk around the living room? Just something to get your body moving. If you can, have physical therapy, or other exercise programs. Again, this isn't going to take away all the fatigue. I don't want to overstate this, but it's just getting your blood flowing and moving if you're feeling up to it.

(23:55): Another area of research is bright light therapy. Historically, this has commonly been used to treat seasonal affective disorder. One thing we're seeing in the literature is that cancer and cancer treatments seem to influence the circadian system. We're still trying to tease this apart, however what we think happens is this. We have a main clock in our brains called the suprachiasmatic nucleus, and it stands to reason that our cells have clocks too, and tumor cells probably have clocks. We think that bright light therapy is effective – we've seen it be effective for cancer-related fatigue – because it's re-regulating your sleep system, your circadian system. What we're seeing is that systematic exposure to bright light helps to normalize these rhythms., There are pilot studies, some by Sonia Ancoli-Israel, that show it may prevent fatigue. Remember, we are prophylactically trying to prevent fatigue, and or treat fatigue, in patients with cancer and survivors.

(24:57): I often recommend that my patients get a HappyLight or one of the similar lights on Amazon. They're the size of an iPad and relatively inexpensive. You use it for 30 minutes each morning. It's important to use it in the morning, not in the afternoon or night, because light can impact your sleep. Use it every morning for four to eight weeks, bright light, broad spectrum. Again, you can find these on Amazon. It's a small lamp. The ones on Amazon look a little bit bigger. They're the size, again, of an iPad, and you keep it at about a 45-degree angle at an arm's length away.  

(25:36) There are also light goggles. The only caveat with light goggles is that, if you're sensitive to light and have migraines or anything going on in the brain, we don't recommend them. They're also quite a bit more expensive than the lamps. But light is important, in general, for us as humans. It's why seasonal affective disorder exists, for those of us in the Northeast and other areas where it's dark.

(26:06): The bottom line about fatigue is that it's real. It's different from regular fatigue. It's common, severe, impactful, and long-lasting. The causes and mechanisms are unknown, and although we suspect we understand why it's happening, there's more research to be done. There are a variety of tools to help treat or manage cancer-related fatigue. For fatigue specific to CAR T-cell, the literature is new. A lot of this research has been done in breast and prostate, but we're expanding, we're moving. I'm doing some of this work to try to figure out how it looks different across disease states, and with treatment. Stay tuned for that.

(26:50): Cognitive behavioral therapy for insomnia (CBT-I) can help with sleep which in turn can help with fatigue. Let's talk about cognitive behavioral therapy for insomnia (CBT-I). I focus a lot on fatigue, but I don't want to miss out on the sleep health component of it. CBT for insomnia was developed about 25 to 30 years ago. If you've heard of cognitive behavioral therapy in general, this is a little bit different. It's more behaviorally focused, typically six to eight sessions, and it's super robust. I'd love to say it works for a hundred percent of people, but I can't say that. But it works for a lot of people, and it works for cancer. We're running some trials on this now, and I will share those slides with you in a few minutes.

(27:35): The way this works is that we ask folks to keep a sleep diary. With that data we set a standard schedule for your bedtime and your wake time. In cancer, the wake time is very important, coming back to that circadian system. Circadian is our alerting signal. It wakes us up in the morning. If you want a strong circadian system, especially if we suspect that cancer is dysregulating that, you want to try to get up at the same time every day. CBT-I works on both 1) your sleep system, which puts you into bed at night and hopefully keeps you asleep until you wake up in the morning, and 2) your circadian system, by giving you a schedule, ensuring that you're tired enough to go to sleep, and that you're able to wake up at the same time every day.

(28:23): Right now, we don't have enough CBT-I providers. At Penn we have the Sleep and Cancer Clinic. If you're in the Pennsylvania area, that exists, your oncologist should know about it and can refer you over. However, there are CBT-I providers throughout the country. We're still growing this field. The broader field called ‘behavioral sleep medicine’ is relatively new when compared to other fields in medicine. The first paper was in 1987, so we've grown quite a bit, but we're still trying to train people up. If you google ‘CBT for insomnia provider’, a provider directory should pop up and hopefully you can find someone in your area, or somebody who provides telehealth services.

(29:26): The Sleep and Cancer Clinic, which I developed in collaboration with the Department of Psychiatry, began in February of 2024. We, mainly I, provided CBT for insomnia and cancer-related fatigue management to patients diagnosed with cancer and to cancer survivors, i.e., patients across the diagnostic spectrum. We assessed treatment outcomes with what we call the Insomnia Severity Index and the Brief Fatigue Inventory. And we also looked at something called sleep efficiency, which we calculate based on how much time people are spending in bed and how much time folks are sleeping.

(30:13): I also provided information and education to oncology teams on how to identify insomnia and fatigue in the context of cancer, so patients can get referred appropriately. Providers were encouraged to refer patients with insomnia and or cancer-related fatigue. This was predominately a telehealth clinic, because . I did this because  ,we have folks coming from all over the place, so I wanted this treatment to be as accessible as possible. Folks also could come in person, but most people opted for sessions conducted via telehealth.

(31:04): I looked at reach (the number of patients referred divided by the number of patients scheduled for an intake) and retention (the number of patients who completed treatment divided by the total number of scheduled patients). From March 2024 to February 2025, we had 78 patients referred, and 44 completed intake, so we reached over half of the people, about 56%. In terms of who we retained, 26 patients out of a total of 44 scheduled patients completed treatment, so we were able to retain about, about 60% of folks. Some reasons for loss of follow up were that we had some folks pass away, and we had some folks who went back into treatment and felt like it was a lot to do this at the same time, which is totally fair. Overall, what we're seeing in the treatment of fatigue and insomnia in the context of cancer is that we are able to reach and retain folks and help them with their symptoms.

(32:25): Of the 44 patients who completed treatment, I have included 13 subjects in the following analysis. The analysis excludes patients who did not have pre-deposed data. Either I was in the process of collecting those measures, or they received only fatigue management  not both insomnia and fatigue management. So the subsequent slides include data on 13 subjects, including their demographics, pre-post insomnia data, fatigue data, and their sleep efficiency.

(32:57): We had primarily females, comprising about 85% of our sample, and most were white. The mean age was about 62, with a standard deviation of 14.7. What we see in this graph is that the insomnia severity index (ISI) is 14, which is moderate insomnia. At post-treatment, we were able to decrease their insomnia to mild, at 6.2, which was about a 56% decrease, with an effect size of three, which is a big effect.

(33:38): The Brief Fatigue Inventory (BFI) was 4. Anything above 4 is considered moderate to severe fatigue. After treatment, I was able to get them down to 2, which is great. That's below the significant threshold, with a percentage change of 50%.

(33:53): For sleep efficiency, we're often aiming for folks to be above 85%. On average, people came in at around 76%, and at post-treatment we had them up almost at 92%, which is a percentage change of 21%.

(34:08): Early studies suggest that CBT-I can improve both sleep efficiency and fatigue.  Although this is a small sample, I wanted you all to see the effect that CBT for insomnia can have, not only on sleep, but also on fatigue. We think this has something to do with our ability to consolidate sleep, and its effect on the daytime.

(34:29): Here's a graph representing our pre-to-post change in insomnia, and here's our fatigue pre-to-post change; our sleep efficiency went up quite a bit.

(34:49): Another study that we're doing, related to breast cancer, is looking at the effects of CBT for insomnia, on insomnia of course, but also fatigue. When I was in my fellowship, I was thinking a lot about the studies that I was reading, and I noticed they were reporting fatigue as a secondary outcome, and they were doing CBT for insomnia. After about six to eight sessions, the manual is eight sessions, the effects weren't that great. I thought perhaps that was because we were giving the same number of sessions that we would give to somebody who doesn't have cancer or hasn't survived cancer. Maybe we need to increase the number of sessions to see more of an effect on fatigue. If we hypothesize that part of fatigue is related to disrupted sleep and circadian issues in the circadian system, then it stands to reason that maybe we need more treatment to regulate this.

(35:51): So this is what we did. This is from my fellowship, and we're testing it now in a larger sample. These results are from 13 people. We gave the Insomnia Severity Index, which is on the left, and another type of fatigue measure, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT). If you look across the bottom at the x axis, you see the numbers 1, 2, and 3.  They represent pre-treatment at 1, post-treatment at 2, and follow up at three months at 3. The graphon the left shows ISI and on the right you see  FACIT. Not surprisingly, we saw a treatment effect with the ISI, because CBT-I works. It's super robust, and we were able to improve sleep. That wasn't that shocking to me. They went from having moderate to severe insomnia to not really having any insomnia at all.

(36:36): What was more interesting to me is the FACIT results. FACIT is reverse scored, meaning higher is better. If you're around 30, that's moderate to severe fatigue. Once you get up around 40, that's minimal fatigue. What was interesting to me was that the folks in the number of sessions we tested (4-8 sessions is normal; we had 10 - 12 sessions, which was considered higher dose) we saw quite an effect. We can't make a lot of claims, because this is a small sample, but the percentage change was about 69% remittance of fatigue. That got me curious, so we're doing this again in breast, and we plan to write a larger grant where we're going to expand this to other cancers to see if we get the same effect across different diagnoses.

(37:20): We think that consolidating sleep and fixing sleep health seems to have an effect on fatigue, but it doesn't explain all of what's going on with fatigue, as I said earlier. But CBT-I does seem to help a little bit, so sleep is important here. Just a note – historically the literature has said that sleep and fatigue are distinct entities, and that fixing one will not fix the other, but we're starting to show that that's probably not true.

(37:47): Future directions include:

Expansion of services – as I said earlier, we need to increase the accessibility of services, including to underserved populations.  

Research and innovation – we need more research on novel treatment approaches to CRF, especially in transplant and CAR T. We don't have enough, very minimal.  

Training and education – enhancing provider training and behavioral sleep medicine, which is our umbrella over the work that I'm doing, to improve integration in oncology care.  

Long term impact – assessing the sustained benefits of treatment and further exploring the role of sleep interventions in cancer survivorship and recurrence prevention. I often wonder whether fatigue is an early symptom of cancer. What if we were able to identify that? Could we diagnose sooner? But that's a different talk for a different day.

(38:40): I want to thank my collaborators, Dr. Gary Freedman in radiation oncology at Penn, and Dr. Michael Perlis in behavioral sleep medicine at Penn, as well as my administrator and research coordinator, Desiree and Mark, and really all of Perlman Oncology, and all of the amazing patients I've been fortunate enough to work with and continue to work with. I will give my email. If you have questions or comments, or questions about receiving CBT for insomnia, I'm always happy to hear from attendees. Thank you, and here are my references. Thank you so much.

Question and Answer Session

(39:23): Steve Bauer: Thank you, Dr. Muench, for this excellent presentation. We will now get to some questions. "My spouse is five months post-transplant and naps a lot during the day. Should I wake him up and get him to talk, or should I let him sleep when he wants?"

(39:53): Dr. Muench: He's five months post-treatment, and again, a lot of the data goes out only three months, but I would try to have some boundaries around naps. I'm not sure if he's not sleeping well at night, but the concern always with napping during the day is that it's going to make it hard for you to sleep at night. If his sleep isn't impacted, I would say you can let him nap, but if his sleep is being impacted, or you feel like maybe it's impacting his mood, it might be worth encouraging him to have some boundaries around the naps. I try to encourage patients to limit naps to before 3:00 PM, so we're not impacting sleep, and limiting naps to around 30 minutes, in bed, with an alarm.

(40:51): Steve Bauer: "Are there any studies for patients affected by fatigue after six years? For example, 10 to 15 years out? I'm interested to learn if fatigue improves over time.”

(41:15): Dr. Muench: I have not seen studies that look at the long-term effects of fatigue, in any cancer, 10 or 15 years out. I could certainly go and dig, and I didn't see any in CAR T-cell. We are currently running a study  in Radiation Oncology at Perlman at Penn, where that is our goal. So stay tuned, but I don't think that data exists. It should exist, but oftentimes researchers stop thinking about it after treatment has ended. That's slowly shifting. We're going to have some three-year data coming soon, so look for that publication.

(42:09): Steve Bauer: “Could you repeat the name of the app to track the energy that you recommended?”

(42:18): Dr. Muench Yeah, it's called the Visible app, V-I-S-I-B-L-E. Visible. Patients that have used it really liked it. You have the option of getting the Polar arm band with it, which costs a bit of money, but if you're able to do it, the patients that I've worked with have found it useful.

(42:47): Steve Bauer: "Is it possible to ever get back the same level of energy after your transplant?"

(42:57): Dr. Muench: I think it really depends. I try to encourage the patients I work with to think about, and work through, some of the understandable feelings about their role changes, and to find a way to still maintain doing the things you enjoy doing, realizing it might look different. I know that isn't the answer that people often want nor that I want to give, but I think it really depends. It does seem like in CAR T, based on the literature, there is more of a chance of coming back from fatigue, versus other diagnoses. I think it's about managing the fatigue and keeping your energy stores level. And remaining active and engaged in your life.

(43:59): Steve Bauer: "The recommendation of no screens before bed, does that include TV? My wife and I like watching music videos. Is there a difference between TV and computers, and that light, and impact on your sleep?"

(44:17): Dr. Muench: What I tell people is it depends on where you're doing your screen time, and the type of screen time you're engaging in. I think screen time can be fine if you're not doing it in bed. The rationale for this is, if you've ever heard of Pavlov's dogs, he paired food with a bell, and over time the cue for the bell was all that the dogs needed to salivate. They didn't need to see the food.

(44:45): Humans make the same kinds of associations all the time, and we do it with bed, too, so if the bed becomes paired with wakefulness, and you're predisposed to insomnia, like in a stressful situation such as being diagnosed with cancer, or having CAR T-cell therapy, you will be more likely to be awake in bed. If you want to watch music videos, which I think sounds awesome as an avid music lover, that's totally fine, just do so in another room. I know there's been a lot about blue light for somebody who's a night owl, or up really early in the morning (think of our night shift workers), but if you don't have what we call circadian rhythm disorders, a little bit of light isn't going to hurt you.

(45:33): I will add, though, to be mindful of the content that you're taking in at night. Try to limit what my kids call doom scrolling, watching things that are going to make you anxious. Those types of things can make you feel more anxious and aroused, so again, music videos sound lovely. If you're doing it in another room, not in bed, I think that's totally fine.

(46:02): Steve Bauer: "What are your thoughts on Ambien-type medications when you've tried CBT, sleep studies, and are seeing a sleep hygiene specialist, and nothing else seems to work?"

(46:17): Dr. Muench: I'm not a prescriber, so any information I provide on medication is solely from the research and what I've seen anecdotally. It's really up to you and your prescriber. If the medication is working for you, and you're not having side effects, it's probably fine. I'm certainly not anti-medication. Sometimes those medications – the Ambiens, the class of drugs is called benzodiazepine receptor agonist (BzRA) – can cause daytime sleepiness, or they don't always work for long periods of time. They're often best used in short-term situations, but if you find that it's working for you, and your prescriber agrees, I don't really take issue with them.

(47:11): Steve Bauer: "Is a morning cup of coffee helpful or harmful in the overall fatigue cycle?"

(47:16): Dr. Muench: I think everything in moderation. I don't think having a normal cup of coffee in the morning is going to impact your sleep too much. The half-life of coffee depends on your metabolism, but let's say it’s somewhere around four hours, so I think a cup of coffee in the morning is fine. I even recommended the nappuccino, if you're already a coffee drinker, a little four to eight ounce cup of coffee before you lay down. Test that out, and if you find it impacts your sleep, don't do it. But I think coffee can be helpful and give you that little boost.

(48:01): It's similar to using stimulant medications in fatigue. It's a similar kind of rationale to if your doctor were to prescribe you something like modafinil, which is a stimulant for cancer-related fatigue. I think it's fine.

(48:18): Steve Bauer: “What are the medications that are safe to take for fatigue?”

(48:28): Dr. Muench: Just to reiterate, I'm not a prescriber, but what we've seen in literature is that they've tried modafinil, which is a stimulant. There's been some work with corticosteroids. Again, it's not going to get rid of your fatigue, I think at best it takes the edge off, which isn't a bad thing, especially during treatment. There have also been some trials with antidepressant drugs like Wellbutrin. These are all options that you could certainly bring to your treatment team.

(49:02): I've had mixed results.  For example I might have a patient in the throes of treatment and reach out to a doc and say, "What are your thoughts on modafinil?" A lot of times docs will say, "No, I don't know. The research isn't that great." It's really up to your medical team.  If you're working with palliative care, they often know a lot about these drugs and what may or may not work for you.

(49:26): Steve Bauer: "I had R-CHOP chemo before CAR T therapy, and CAR T definitely caused more extreme fatigue, which has improved over the two years since my treatment. Why is fatigue so persistent?"

(49:40): Dr. Muench: Oh goodness, that is a wonderful question, something I think about from the moment I wake up 'til I go to bed. I am not sure. There are some hypotheses that have been proffered. There's been some animal work in this arena, but it's very new and preliminary. – When you have cancer or anything, that causes your immune system to go into overdrive, like long COVID or chronic fatigue syndrome, you can think of your immune system like a light switch. Your immune system goes on and there's no dimmer, and because of this there are some neurobiological effects, effects to the brain, that cause the fatigue to be virulent and persistent. This is just a hypothesis, we aren't entirely sure, but we are working to figure it out.

(50:42): That’s why it’s helpful to use the fatigue package that I was talking about – bright light, making sure you have good sleep health, and activity pacing – these things are important, because they not only take the edge off, they also keep the fatigue in check, so that its not getting worse. Again, think of the pain analogy. We're not going to wait to take our pain med until the pain is at a 10, we want to keep engaging in these preemptive behaviors to maintain quality of life.

(51:14): Steve Bauer: "Have you seen any trials with Vyvanse, V-Y-V-A-N-S-E? I took the brand version for 2024, and found it helped some days, not all, but found the generic versions didn't help at all."

(51:32): Dr. Muench: I can't speak to the generic versus on label versions, and I haven't read the literature, if there is any literature on the use of Vyvanse for cancer-related fatigue. But like modafinil, it probably will help a little bit, in the way that coffee would help. It just isn't getting at the mechanism of fatigue. Let's say after treatment you take Vyvanse. It might not have worked well because it's not targeting the place in the brain where fatigue is emanating from, because we're not quite sure what's going on there. But I'm glad it worked for you a little bit, and now I feel prompted to read the literature, because somebody else brought it up to me as well.

(52:32): Steve Bauer: "Caffeine has never impacted me. It doesn't work for waking me up or helping me stay awake. Would nappuccino work for people like me?"

(52:42):Dr. Muench: Maybe. I think the reason why it takes some of the edge off is because you're also taking a nap. When we get really sleepy, it’s because something called sleep pressure builds, and that's driven by a chemical in our body called adenosine. Caffeine blocks adenosine, the chemical that's building up in our body when we're sleepy. That's why we think it's a little bit effective, because you're knocking off some sleep pressure when the caffeine is blocking adenosine. I would say, give it a try. Again, a reasonable amount of coffee. I'm not recommending a Monster Energy drink, but it might help you just feel a little bit restored.

(53:27): Steve Bauer: "What about being outside in the morning as a bright light source? How early, and for how long, would be useful?"

(53:35):Dr. Muench: The sun is the best. I recommend a light box only if you're in the midst of treatment, or you're not feeling good, or you live in an area where it's hard to get outside. I live in a city and sometimes there isn't a place for me to go. But sunlight, at this time of year, if you live in an area where it's good weather, it's not too hot, I would say take a walk. Make sure you're wearing your sunscreen and your hat, of course, but take a walk, whatever feels good to you, because that’s also combining exercise, which is great, and getting yourself moving. It depends on what feels good to you, sometimes people go out in their backyard and they sit in a chair, in a shady spot. But natural sunlight is the ideal situation.

(54:27): Steve Bauer: "How persistent is fatigue after an allogeneic bone marrow transplant, compared to after CAR-T cell?

(54:42):Dr. Muench: I will look this up specifically, but I think with allogeneic the fatigue is a little bit worse, but I think the effects weren't large. Again, for CAR T cell, more work needs to be done in terms of what's happening during treatment and what's happening after treatment, and having studies that look out past three months would be useful. Let me see if I can put up this slide up so you can email me, and I can get you a better answer with some definitive data.

(55:29): Steve Bauer: "I feel that people may judge me for taking breaks if they aren't aware of my situation. What's a good way to deal with that, or let people know?"

(55:41):Dr. Muench: This comes up a lot. I'm not sure about your specific situation but when I say taking breaks, number one, I think it's really dependent on your situation. Oftentimes with my patients, if they have busy schedules or work or something like that, a break can be even five minutes. And if somebody is expressing judgment towards you, then if you feel safe to do it, communicate, "Yeah, I think I just need a break, and I'll be back at it in X amount of time."

(56:16): But this is a larger conversation around communicating. In certain types of cancers, or in a lot of them, you can't always see how unwell someone's feeling, so people forget. It's not that you need to remind people every second, but just say something like, "Hey, you know what? I'm going through this," or "I just need to go take a break." Sometimes I even encourage people to go to the bathroom. If you're feeling super self-conscious about it, which is understandable, no one's going to follow you to the bathroom. Just saying, "I need to use the restroom," excusing yourself and taking five minutes or so, depending on how long you want the break to be. I could do another whole lecture on role changes, and communicating, and feeling safe to do that. I wish I had more time.

(57:09): Steve Bauer: Closing. On behalf of BMT InfoNet and our partners, I'd like to thank for a very helpful presentation. And thank you, the audience, for your excellent questions. Please contact BMT InfoNet if we can help you in any way. I hope you have a great day.