(Guest Lecture) September 2022 - Improved Fitness = More Options

Thank you so much. I think that's actually a good topic right after lunch. I feel fairly happy right now. The fitness is something that it came to me, this topic came to me. Well, I love doing workout myself and my patients when, as I said, when I started treating myeloma, it was many moons ago and we did not talk about fitness, quality of life or any of that because we talked about how can I keep your life a little bit longer. Now we thankfully have many new drugs and can prolong the life of patients and now quality of life is important because I said our credo in our department is as long as we cannot cure myeloma, we want to at least make sure that our patients have the best life they can live. Topics why exercise matters even a little bit and that's something that Greg added and I can tell you Greg actually lost a lot of weight, I think, right? You're really in great shape. I saw him in Utah hiking up a mountain like it's nothing. So that's pretty cool. He's a really role model. 40 pounds, see that's awesome. I didn't ask you if I can tell anyone, but it was so impressive to see you run up this mountain in Park City. So that was nice. And then the 10,000 steps, the magic 10,000 steps. I will talk about that a little bit and then stress, exercise, psychology, what's going on in our minds and combined with our body. I think those are very interesting topics. There are several challenges. If we talk about fitness in myeloma, there are challenges. Obviously bone disease is one of them, right? When I started treating myeloma and again, I say this sentence, patients with oscillatory lesions, I had no clue. Can they do work out? And some people here in the room had discussions with me about that. What can I do? How much can I lift? How high can I jump? And initially we had no idea if that's okay, if there's a risk. As you know, myeloma causes a disbalance of the bone building and the bone eating cells. And the bone building and eating cells, they are completely healthy. They're just overactive, the bone eating ones and the bone building ones are a little bit inhibited. And that leads to these osteolytic lesions and to the osteoporosis. In the worst case, it leads to fractures. This is kind of a scheme, how this, how it works, how these cells, oh, you know what, just brief interruption. I turn off these lights so that you can see the slides better. Right back. It's a bit better to see, I think. Yeah. So this shows the bone eating cells, the bone building cells and the myeloma cells. And it's kind of a vicious circle, right? The bone eating cells get nutrients out of the bone that then feeds the myeloma cells and the myeloma cells stimulate the bone eating cells. So these are the things that we have to deal with in myeloma. And you know, we give bisphosphonates, we give denosumab to prevent that, but there are other things that we can do as well. So our goal in myeloma is from here on the left side, you see an osteolytic lesion. Usually that should be all this light gray scale, right? That's a CT of a vertebral body. And then we give treatment and in some patients, not all, again, we don't know enough, but we are getting there. In some patients, we see how the body starts to rebuild bone. Can you see that? There's this white rim around this hole in the bone. And that's something that we want to see in our patients. And obviously our treatment, bringing the myeloma under control, giving bisphosphonates, giving denosumab, that should help. But there are other things that we can do on top of that. Another thing is, and please don't read all that, this is only showing you as we discussed earlier, the immune system of myeloma patients is compromised because the myeloma, if cancer develops in the body, the immune system was not able to stop that because every day in every one of our bodies, there are cells that go wrong. And then the immune system says, you're wrong. I have to kill you. If a cancer develops like myeloma, then there's this kind of this gap in protection in the immune system. And these are scientific data where myeloma has an effect on the immune system, weakens the immune system. That's where the infections come from. Then obesity is also something that we know about. People who are obese have a higher risk to develop myeloma and have a higher risk to die from myeloma. So being in good shape is actually good for your survival chances as well, and not even to develop myeloma. But I'm sorry, this frame's a little bit off. But it has been shown that if you, if patients are more obese, they have a higher risk to develop myeloma. So starting with the bone, what can we do to improve bone other than with our treatments? And as you might know, if when astronauts come back from outer space and now they stay longer and longer in the International Space Station, they come back and they are osteoporotic. And those people, I mean, they are the fittest on the planet before they leave. And then they come back and have bones of a very frail old person, even though they're still in their 20s and 30s. So what they do is they do weight lifting. Well, there is no weight in space. So they have to be very creative. And so they have very interesting ways to deal with that. But it shows that they have learned that they have to strengthen their bones by working out, by using our bones, our body always. What we don't use kind of fades away. And in space, they don't have any weight on their bones. So the bone fades away because the body thinks, why should I invest in something that I don't need? Right. And that's why they have to put pressure on their bones. And that's something that we can learn from them for multiple myeloma. Then there are different things that you can do. You can run, you can swim, you can do other things. Conventional is conventional in this. And so they did studies, not specifically in myeloma, but in other patients or in healthy controls where they measured the effect of exercise on bone density. And bone density, we want a high, highly dense and strong bone. And so they see that running seems to be the most, the least, the most effective way or combination of things seems to be the most effective way to bring the bone to redevelop. Swimming takes away gravity. So we have this effect like almost like in space where swimming is still a good thing, but it is not as effective as, for example, running. The problem with running again is that there's an impact, right? Every step that you run, there's an impact on your spine. And that's something that you have to discuss with your doctor in most of your cases, me, to be sure that this is not too much for your bones. And this is again, a lytic lesion. And you can see if there's this, where this blue arrow is on the right-hand side, you can see that there's a piece of the vertebral body missing because the myeloma has eaten it up and has over-activated its bone-eating cells. And there you can see that there's a high fracture risk because there's no stability anymore because bone is, as you know, very strong material. And if that is the case, we have to be very careful with things like running. Then coming to the immune system, that's really good. Again, this is just kind of a picture to show you. There's a lot of things that are going right when you work out. Work out physical activity, has a beneficial effect on most immune cells. There again, don't read all of that, but some of the cells, and we talked about the T cells, they can be, can kind of be woken up, can be, become more active, can be less exhausted. And that is something that we need for our immunomodulatory drugs to get good CAR T cells and all of that. So if we keep our immune system happy by working out, that's definitely beneficial. And these are the effects of exercise on the immune system. We don't know how much this works in myeloma and the current study will investigate that. We have first pilot data that will be presented at our hematologist's meeting, so I cannot talk about it yet, but I can tell you it's encouraging. So what we have done with the help of Health Tree is that we sent out questionnaires on the Health Tree platform and asked how much, and maybe some of you have participated, how much exercise or physical activity have you done? How many hours per week have you done before you got your diagnosis? How many do you do now during you have the disease and what would you actually like to do in the future? And we saw that there's a clear drop. Even patients with MGAS who should not have a problem just knowing about the diagnosis seem to have a negative effect on their physical activity, so they were less active. And almost every patient said, I want to do more than I'm doing right now. So that is definitely an urgent need to get more data. So we asked in Health Tree, we got feedback from 794 patients within a few months, which is awesome for the research and me, like the kid in the toy shop. That was really cool to get it very, very quickly, a lot of answers. So we had a lot of myeloma patients, some small, some MGAS, median age of myeloma patients. And unfortunately, fortunately, I don't know, Caucasians seem to be more engaged in that. I would like to see more African-Americans also to be engaged because they have a little bit different immune system sometimes. So we would learn from that as well. I guess most of you know the history in this country and also other countries, which is the reason why they oftentimes don't participate in clinical trials. But we do have some patients also responding on that. And again, I cannot really show you the results, but in three months from now, I can show you. So stay tuned. And we have a new study now where we build on our pilot data. We have a prospective trial with three cohorts. One cohort is doing exercise remotely twice a week for six months. So we have learned it has to be quite some time, as you know, our body changes not that quickly. And the older we get, the slower our body changes. So that's something we will measure immune markers. We will measure bone markers. We will measure quality of life markers, psychological markers, like depression, anxiety. And we want to see what the effect will be of this exercise. That's one cohort. The other cohort is intermittent fasting, because as I said, obesity is a factor. I have to admit, back in the day when patients asked me, I heard fasting is good for cancer patients. It doesn't matter. Cancer cells just take what they want. There's actually data literature showing, scientific literature showing that fasting, healthy cells can adjust to fasting state much better than cancer cells. So cancer cells actually starve when we fast. Should not be too extreme, because obviously our bodies can be weakened by that too. But there seem to be positive effects. And that's something that we look at in our cohort too. And in cohort three, only for newly diagnosed patients, we look if beta blockers that block the negative effects that stress can have on the immune system. We use beta blockers in combination with myeloma therapy. So these are the three cohorts. And the exercise is the largest because we have the preliminary data. The intermittent fasting is very early. So we only have a few patients that we can enroll, but please approach us if you're interested and participate. Briefly, about the 10,000 steps, the large women's health study where they screened hundreds and hundreds of people, healthy controls, found out that there is more steps per day is better. And I get no money from Fitbit, unfortunately, but I use the Fitbit. You can use whatever brand you like. And it helps me too, because I'm a little bit competitive. So I like to be beyond the 10,000 steps, but what they actually found, the not magic number, but the number that's actually scientifically proven is 8,500 steps, which helped me because I sit my butt so much, because I have an office job other than when I'm in clinic and getting up and walking 8,500 or more steps per day seems to be beneficial. You can see this benefit kind of flattens out. If you walk 20,000 steps, that's awesome, but it doesn't make a lot of a difference in this setting. So 8,500 seems to be where 8,500 and more seems to be good to be active per day. And as I said, these step counts seem to help. And here's just a show. They looked actually into other things than cancer, but it was beneficial to have this around 8,500 steps. And then also what we learned, and my wife should actually give this talk because she's a nurse and now a personal trainer like Lindy, who will train you later. And she looked into the literature for multiple myeloma as well. And again, this is not literature for myeloma. We are building this literature right now, but in other control groups, they found that if you sit for eight hours straight, which unfortunately a lot of us do, and work out after, the workout basically does not do anything for your body. So this sitting eight hours straight is so bad that after that, not even workout can save you. So what I do now, and that's another thing that my watch can do, it tells me every hour to get up and walk a few steps. And they did actually, they did four second sprints, just not sitting eight hours straight, but interrupting the eight hours straight sitting with four seconds sprints, just getting up a little bit was helpful and those patients had much more benefit from what they did later on with their workout. And these are really easy things to do. Just set a timer for once an hour, get up and walk a little bit. So that's another recommendation that we have. So why would we promote Health Tree here? Again, I get no money from them. I like working with them because Greg and all the team is, they're awesome people. But for us, if you enroll in Health Tree, and it's a little bit promotional, but I really believe in what I say here, it will advance the field. Nathan earlier asked me about a few things and said, hey, no one has ever looked into that because no one has access to so many patients. You heard from Jenny that it's 10,000 more patients. That's awesome. So if you enroll, you can decide which information you give, but every information we get is helpful for research. So you get also access, obviously, and you will hear more about that. And you are in close supervision. So you get feedback from people who can connect with others and hear what they do. Yeah. And for clinical trials in general, as Dr. Gertz said earlier in our round table situation, he said you get much more attention, obviously. The monitoring is much closer because the study demands it. So being in the clinical trial is good for you as well. And oftentimes it even reduces the costs because the sponsor of the trial pays for the drug, pays for the treatment. And for our research, obviously, to find the cure, we have to do clinical trials. We cannot do anecdotal stuff. We have to do clinical trials. We can create new hypotheses, especially Health Tree helps us with that because that's real world setting. So we know what's happening, and then we can find patterns in this large number of patients. And we have easier access through Health Tree, and we can then approach them with interesting stuff that might not be interesting for a pharma company, but it is interesting for the myeloma community. So my recommendations from a fitness perspective, and I'm happy to talk about that in smaller setting later on, talk with your doctor first if your bones are strong enough to do certain stuff. Set achievable goals because if you say, okay, tomorrow I want to run a marathon, that might not happen. Maybe some of you, but not everyone, definitely not me. Get your steps in. It doesn't have to be 10,000, 8,500 and more is great. Aim for, that's the general recommendation, 150 to 300 active minutes per week, depending on how strongly active you are. That is something that you could do. And even a walk outside can be already part of that. Don't sit too long in one spot, but get up and walk and then sit down again. And combine aerobic and resistance training, because the resistance training helps with the bone strength. Don't lift too heavy because that's harmful for the bones, but some might be helpful. And then my recommendation, which is still on Health Tree. Thank you so much.