(Guest Lecture): September 2023 - Treatment-Free Ways to Delay Progression

Good morning. As I introduced before, I'm Betsy O'Donnell. I'm a multiple myeloma provider, but I actually also am board certified in something called lifestyle medicine. And so you've heard a lot about treatments and a lot of trials. And so today I'm going to actually talk about something you may not have formally talked about at any of these conferences before, but probably have asked a number of time for questions about nutrition and exercise. And I also mentioned we have some clinical trials in the microbiome, so I will get into that. So that is going to be the lens of this focus is on lifestyle medicine and specifically are there treatment free ways to delay progression. And so what is lifestyle medicine? So lifestyle medicine is the evidence based practice of incorporation of things like exercise, nutrition, sleep, stress, relationships and substance use. There are six specific pillars that comprise this. And again, the evidence, it's focused on evidence based medicine. And so why do we care about this? I think we all go home from our treatment centers no matter where they are. And we ask ourselves, what can I do in my life that may help me have a better outcome? And these are understandable questions. So as a general practice, attention to things germane to lifestyle medicine can improve quality of life, may potentially improve side effects of therapy, your physical function, mood, your level of fatigue, and even potentially your cancer outcomes. So I'm going to go through each of these six pillars. I will say that there is not a lot of data, unfortunately. There is a paucity of information specifically within plasma cell disorders about these topics. Several years ago, during the pandemic, I worked with my research coordinator to put together a compilation of all of the data for these six pillars. It's published in Blood Cancer Journal. But what I can tell you is that our conclusion in a number of these is that there is a paucity of evidence. So why do people exercise? What do we know? OK, these are studies that have been done in cancer patients. So exercise can improve quality of life, can decrease cancer-related fatigue. It's one of the few things that's actually been proven to decrease fatigue, decrease anxiety, improve emotional well-being. Libido can improve your sleep as well as social functioning. A critical question is exercise safe and beneficial. Exercise is safe with the caveat, and I'm going to talk about some caveats in this population in multiple myeloma. This is a discussion particularly as bones are very often involved. You must have this conversation first with your oncologist, and also there may be resources to help with strength and conditioning, particularly after you've had a bone-related event. So what is the American College of Sports Medicine, which is what informs the American Cancer Society? Historically, they've recommended 150 minutes of moderate or 75 minutes of vigorous activity per week with resistance training twice per week. There were updates in 2019 that demonstrated there's actually evidence for benefit of just doing 30 minutes three days a week. So when you think about all of the factors in your life, even just small amounts, and I will also say that 10 minutes three times a day will garner the same benefits of 30 minutes at a time. What is light exercise? So light exercise is no significant change in your breathing pattern if you're out walking. If you're walking hard, you can talk, but maybe not get a whole song out. And then vigorous activity would be saying a few words, but without having to stop to catch your breath. And so here are some general principles, and a lot of people either have an exercise in their life or can exercise, but are curious about it. So choose an activity you enjoy. Don't try to do something that doesn't appeal to you because you are less likely to want to do it. Start slowly. You do not need to hit that 30-minute target. And if you have not been exercising, I would start with 10 minutes even, nothing more than that. And even start light and build up. This is something that needs to be a progression, and it really depends on where you're starting from as well. Try to do it at least every other day. And so, trying for that moderate intensity and try classes. Try things that engage you and make you feel a part of something. Support is critical. If you are someone who wants to be more active, and we have different events for cancer patients, you see 5Ks and things like that, often advertised. Talk to someone first. I'm going to get into that in a slide in a moment. Set short and long-term goals. Find a friend or a partner. Engage with people. Most of us have devices now that calculate our steps. Steps can be the easiest way to get exercise in, but set goals for yourself on a daily basis. And if anything else, this is probably the most important slide about activity, is to avoid inactivity. When you have a new diagnosis in particular, there will be a flood of people who want to help you doing things for you. And unless you have specific bone-related issues, try to keep doing all of the things that you can do to help you. And we talk about frailty. We often talk about the activities of daily living and the instrumental daily, excuse me, activities of daily living. And these are the things that you do within your household. But they are also predictive of outcomes. So the greater independence that you preserve, the better you will do over time. So cancer rehabilitation is a really important one. And we have a lot of people who are trained in physical medicine and rehabilitation or physical therapists that can assist you. Physical therapy is covered by insurance. If you ask your doctor for a referral, you may be eligible for physical therapy. And the billing codes that are available are things like cancer-related fatigue, cancer-related deconditioning. And I think that is a very safe way, particularly in this population, to engage in exercise. Start with a physical therapist. If anybody's ever been to physical therapy before, they do an assessment. They see you more frequently at first and they graduate you out. That is what I would argue is probably most appropriate for anybody who has multiple myeloma and bone-related diseases. And so I talked about this, but physical therapy obviously is what I was just alluding to. So before you start, you should be screened by your provider and have this conversation with them. But I think many people should understand that when you are on medications like dexamethasone, that will decrease your lean muscle mass. That is a known side effect of that medication. So preserving what you have in terms of your muscle mass is critical and obviously potentially augmenting it if you've lost muscle tone over the course of your therapy. The next thing I'm going to talk about that is so relevant to this room is sleep. And so sleep is extremely important. We spend up to a third of our lives, if we're lucky, asleep. Our brains are active during sleep. They are not turned off. There is a lot going on. And it affects not only our sense of wellness, but it also affects our mental function, our mood in particular. So how much sleep do we need? You know, on average about seven hours should be a target for everybody. But sleep disorders are very common, and particularly when you're on medications such as dexamethasone. Some people are not affected by dexamethasone, and that's wonderful, but the majority of people are. It is our least important in terms of the efficacy when we think about drugs like daratumab, lenalidomide. We can decrease the doses. You do not need to be a hero and stay on 20 or 40 milligrams if it's keeping you up all night. The goal in all of myeloma therapy is continuous therapy, and so having a lower or even no dose may be better for you if it means that you have better sleep quality. So if you are suffering from insomnia, because very often, and I'm guilty of it too, we don't ask our patients, how are you sleeping? But if you are, bring that up with your oncologist, and they will decrease that dose, and that may be very important. Also, make sure you're taking in the morning when you get up with food, okay? And obviously the other huge element of sleep disorders for myeloma patients can be anxiety. And so this is something else that is treatable. And so if that is a component, make sure your team is aware we want to know and we want to help people. So there are some things that you can do. Sleep hygiene, have a routine, go to bed at the same time, get up at the same time. My dog knows what my bedtime is, and she will woof at me at 10 p.m. if I'm not headed upstairs. So it does make a difference. Set a stage, wind down, you know, stop doing for a little bit before you try to go to sleep. And what can you lose? Any substances or habits? So whether that's drinking coffee after 3 p.m., alcohol in the evening can actually impair sleep quality. And exercise during the day can make you more tired at night, being active. So try to eliminate things like caffeine, nicotine, and alcohol. High sodium foods. Don't eat late at night and power down those screens. The blue light from your screen actually activates your brain. So when you're on your phone, which suppresses melatonin, melatonin is something we make that makes it in our own brain that makes us sleepy. And this interrupts the circadian rhythm. Do nice things for yourself. Why not? Take a warm bath or shower. Do some stretches, read a book. Do things that condition you to want to go to sleep. One of my colleagues, this is not advancing. I'm not advancing here. There we go. Sorry. One of my colleagues back at MGH used to put together playlists. And so soothing music can also be very helpful. Social connections. How many people talk about this? But this is really important to your wellness. Having people you're connected to. This here today is a social connection. Finding people who are having an experience similar to your own. You know, during COVID, it was a very isolating time. And we all learned the importance of being around other people and what that means to our lives. It is particularly important to us. When we look at social connections, we know the single most important predictor of human happiness and longevity is having strong social connections. This was a lovely paper that was published several years ago. Health related measures like blood pressure and heart rate improve even with short positive social interactions. And so we know that cancer can be isolating whether it's because you're spending time in the hospital getting cartilage surgery or something like that. Or because during COVID you could not go out and feel safe. These are isolating times and they can be emotionally isolating as well when you don't feel that you can share with people the unique experience that you're having as a cancer patient. So support is needed throughout. And people who are caregivers need to recognize that this is a long process and it's not just on the day of treatment or the weeks that follow that this is a long process. This is an endurance race that requires ongoing support throughout the cancer journey. It can alleviate stress. You need to find people you can confide in. Being someone who also is a confidant in a social setting makes you feel good. So as you sit in this room and you share your experiences, I bet most people feel better too when they help someone else who's going through the same thing. It makes you feel a positive interaction and less isolated. Dumb things that some people may say are silly but they really do help. Saying hello to someone, having a smile on your face, it actually makes you feel better as you go through life. Spend time with people. Be there for those who need you and be supportive about other people who are doing your life will actually feedback to you in terms of your own journey. And be careful with social media. Whether it just be the information that you're getting, if you find that it's impacting your mood, be choosy about what you look at. And also be mindful that sometimes what people put on the internet is the highlights reel of their life. And so it may not actually reflect what is actually going on. Stress management is another important pillar. So we know that there is a dramatic impact on the quality of life that we're seeing. There is a dramatic impact of stress on people's lives. I actually worked at the White House during the Clinton administration and there were similar photos and it was really remarkable to see how much the job of being president impacts people. And it affects your whole body. On the cellular level, on the physical level, on the emotional level. I'm not going to go through this slide but this is a whole body experience. So what are some of the antidotes? What are the types of things that may help you feel better? Mind-body therapies. There are cancer centers, whether you're at Dana-Farber or MGH here in Boston, to have integrative therapies that are usually free to patients. So take advantage of those resources. It doesn't need to be every visitor every day but at least try them and see if they help you. Exercise, nutrition, and support. Identify your stressors. Build your coping resources. Some hospitals have psychosocial oncology. If you're not aware of that, I know that both Dana-Farber and MGH do. Where you may be eligible to meet with people who can give you cancer-specific advice to manage some of your stressors. What you think you become, what you feel you attract, what you imagine you create. There's a lot of power in positive thinking so remember that. Meditation receives a lot of attention. I personally don't like to meditate. I like to move. But it may be beneficial and there are all kinds of apps and resources that are available. Find the thing that helps you is what I say. There can be a cascade of events for things like meditation where you can lower your blood pressure and heart rate. There are studies that show improvement in inflammatory bowel disease. And there may be modifications to your brain in a positive way and reduction of physical tension. Focus on self-care. Do things for yourself that make you feel good. It is okay to do that. Try things like yoga if they make you feel good. Try anything, whether it be going for walks or carving out time for yourself. Just to recognize that that's a part of your cancer care. Substance use. People do ask about this a lot so I just want to specifically address this. Patients will often ask, am I allowed to drink alcohol? The less alcohol you drink, the better for you. It is a carcinogen and associated with an ingrown toenail. There are specific chemicals that can be DNA damaging within alcohol. So just be aware of that. The guidelines for the American Cancer Society say that women should not have more than one alcoholic beverage per day and men more than two. Is it safe is a question you need to ask your physician. There are therapies that you can be on. Alcohol specifically can be a good source of antigen. And you can also be on a diet. There are a number of different types of diet plans that you can take. There are a number of different types of diet plans that you can take. There are a number of different types of diet plans that you can take. And you can look at the pattern. When the doctor says you have an antigen. This is how alcohol makes the medicine. And alcohol can have side effects of your clotting ability. And if there is a change in your therapy or if you have a question, it is always best to ask your provider as well. And if there is a change in your therapy or if you have a question, it is always best to ask your provider as well. One of the other big ones that comes up is marijuana. There are data that suggest not done in the United States, so you cannot study class two substances in the United States, but in other countries such as Canada and Israel, there are some studies that have been done that demonstrate the use of marijuana lessens the need for some pain medications. You have to be aware, though, that with euphoria, there can be other side effects that may not be right for you, including increased paranoia and anxiety, so be careful if you do choose to use these things. Our providers who are licensed to prescribe marijuana products, but use them with caution would be the advice I give. A lot of patients who suffer with difficulty with appetite or nausea ask about edibles. Just remember that dosing, we don't know, you're a doctor, I don't know doses appropriately, so be careful because there are different amounts of marijuana in edibles that you might consume, so just be judicious in what you choose and try to use a consultant if you do. There are FDA approved medications that have chemical pure drugs that are based on this concept that you can have prescriptions of. And again, the American Cancer Society official statement is medical decisions about pain and symptom management should be made between the patient and his or her doctor, balancing evidence of benefit and harm to the patient, preferences and values and any laws and regulations that may apply. And last but not least, and I think this is probably something most people would love to talk more about, is what is the appropriate diet? So there are a number of people, including Dr. Maranac, who study this. It is hard because we don't know whether it's your specific diet at a time, your lifetime's diet that can dictate the efficacy of nutritional interventions in your wellness. In general, though, a healthy eating plate looks something like this, where you see fruits and vegetables are half the plate, whole grains a quarter and healthy proteins about a quarter as well. This is a complex slide and I'm short on time, so I'm not gonna go all through that, but we'll take your questions about it. Americans Cancer Society recommends having a community around eating, so again, this whole theme of social connection, be around people who support healthier life choices, who support healthier eating, can be critical for your own success in adopting healthy eating habits. Limit the amount of sugar sweetened beverages. So when you pick things, look at the labels, often there are added sugars. And so it's okay to have sugar that's within foods like apples, for example, but what you would like to avoid are added sugars to beverages in particular. Limit your consumption of red meat. That includes processed meats, deli meats. Consider replacing red meats with poultry fish or plant-based protein sources. On average, try not to eat red meat more than once per week. Limit consumption of fast foods or processed foods. So I had a boss that once said, you shouldn't eat anything that you can't shoot or pull out of the ground. That was said back in 1998. Vito Gambini at the Tupelo Restaurant in San Diego. So I think that's sage advice. Here we are many years later. Try to limit your consumption of things that are heavily processed. And really an emphasis should be on fruits and vegetables. There are broad range. There is something for everybody in terms of fruits and vegetables. You can keep frozen vegetables or fruits in the freezer. You can mix in a lot of things to augment the attractiveness of vegetables. You can try different cooking preparations. So really try to be creative and try to incorporate them in every meal. Whole grains, hummus is something that has a lot of nutritional value. It spices up a lot of vegetables. My kids will eat it. So really try to find more things that have whole grains and also bring together foods that are healthy for you. So eat food not too much and mostly plants is an important take home message. The old American plate, which is the one that looks like the dinner table at my house growing up is on the right. And on the left you see the more modern new American plate which is much more focused on vegetables, smaller portions of protein and the introduction of whole grains rather than white starchy foods. Be mindful. Think about what you're doing when you eat. Ask yourself if you're really hungry. Be honest about if you're stress eating. Give yourself 10 minutes if you're craving something and see if you still want it. Think about your food as something to have gratitude for and be thoughtful about it. Try not to be distracted when you eat because often you eat more if you're doing something like watching TV. Engage your senses. Notice the colors, the smell, the texture. If you're aware of what you're eating, it's also a good way to moderate your consumption of it. Think about the timing. So the role of meal timing and this is something I'm now transitioning to. So how might meal timing affect your metabolic health, your gut microbiome? There are data that were first recognized by Dr. Maranac in breast cancer that patients who fasted greater than 13 hours had potentially lower risk of breast cancer recurrence. That is something that we are actively now studying in the myeloma population. So I wanna tell you quickly about some trials that we have. So very often patients, particularly those who have precursor disease are interested in understanding what they can do to improve their outcomes. As Dr. Nadim said, we don't necessarily treat patients with precursor disease besides those with high risk of smoldering. And so led by Dr. Maranac, we have a trial of 14 hour prolonged overnight fasting and MGUS and smoldering myeloma. This is not the same thing as intermittent fasting, which is where you vary the intervals that you fast. I personally don't like the idea of not eating for all but four hours a day. That would depress me. So I think that this is actually a much more reasonable strategy with demonstrated efficacy, not only potentially for cancer outcomes, but also cardiovascular disease, where there is an up to 14 hour window where you're not eating overnight. This is also ties into sleep where it can also improve sleep quality as well. So we are actively enrolling patients to this study at Dana-Farber. Something that is particularly interesting to me. So during my time at MGH, I founded and was the director of the Lifestyle Medicine Program within the Cancer Center. And behavior change is hard. And understanding the biology of why it may be effective is particularly, I think, important when you're trying to give advice to patients. So as I alluded to before, the gut microbiome are the bacteria that line our stomach. There is burgeoning research across numerous diseases, underscoring the importance that this might have an autoimmune disease and in a variety of different cancers. It's kind of like that old saying, you are what you eat. Well, this is something that we're interested in. There is very little data in myeloma at this point. There are a handful, and I mean a handful, less than five studies that are available. And what we do know is that in patients, there were certain types of bacteria that were seen in patients who were MRD positive versus MRD negative. Not only are there few studies, there are very few patients on these studies. But there is some suggestion that certain butyrate producers may be associated with greater response to therapy. And so there also are data in just one study that they may be involved in progression of disease. So moving from MGUS to smoldering to multimyeloma. But again, the numbers in these studies were very low. And so right now, going on, and if anybody's interested or knows anybody that might be interested, we have a study at Dana-Farber looking at where our goal is to accrue at least 300 patients with precursor disease. And what does that involve? And so no one likes the idea of collecting stool, but it's actually really not that bad. We send you a kit. It has a lovely tote bag that you can use if you need. So and within it, it comes a hat, gloves. There is just a test tube and a plastic scooper that comes with it. The mailing labels are on the package. So everybody uses the bathroom. This is doable for anybody. And really what it will help us do is amass the amount of data that we need to start to really understand these questions and why are they important? Because there are now studies of targeted therapies, things like probiotics that may potentially be usable. And frankly, sometimes the idea of taking a probiotic may be easier than modifying your diet in such a way to get that balance that we need and more doable for people. And I am all for doable. So this is an ongoing study for anybody who's interested. And then this is another ongoing study. So there were data from Sloan Kettering that demonstrated that there was an improved response in certain cohorts of patients receiving CAR T cell therapy based on their gut microbiome. When you think about the bacteria in your stomach, they are heavily affected by things like antibiotics. The longer you have multiple myeloma, the more likely you are to have received antibiotics. So that's one factor that we're studying. But basically, because we are fortunate to have clinical trials of Toclystomab and Cilticell in the smoldering and myeloma spaces, we are looking at the gut microbiome in both of those populations, both as a comparative. Are the differences between people with smoldering and multiple myeloma? And what happens to them when they get these therapies? And the most important question is, if we see changes in response and we see that there's a signature associated, can we come up with therapies, particularly in that one month window as you await your CAR T cells that may benefit you and change your response to therapy? I think this is really exciting work that will help people in their own lives potentially help their outcomes. And also finally, we do have a study of metformin. This is a older medication that's used for diabetes. Again, it has off-target effects that have been suggested to be potentially beneficial in cancer prevention and cancer recurrence. And so also led by Dr. Maranac, we have this study going on at Dana-Farber. And these are some of the criteria for that, but I'm way over my time. So thank you all, and I'm happy to answer any questions. Thank you.