(Guest Lecture): May 2022 - How to Think About Transplant Today - Patrick Hagen, MD | MCRT Chicago Illinois April 30, 2022

So thank you. So, you know, I'm, I'm tasked with the topic of talking about transplant. And I will definitely do that. But just by way of introduction, I wanted to go through a little background so we kind of know where we come from and kind of where we are and then thinking about where we're going. You know, this the first published case of multiple myeloma I have up here was in 1844. It was a 39 year old woman who obviously didn't do very well at the time. Go to next. Because at that time, our treatments were things like rhubarb pills, orange peel, Dover powder and actually leeches were the first ever maintenance therapy used in myeloma. So obviously, think about that in the context as we go forward. So we've really we've come a long way recently. But you know, there's a long track record of I think, of our advancement. So it's good to keep that in mind. Next. So this is some database registry that I think is really important published just a few years ago in 2017. And what this shows, although you can't see it great, those different colors are different ethnic groups over time in different ages. So less than 65, all the way up to our patients older than 75. And so across every different ethnic group and every different age, we've made huge strides in the survival and that's really depicted there. So if you were less than 65, about 20 years ago, your survival of five years was 38%. And as of 2017, that was 61%. And I would argue much better now. Next. So I know we've touched on this a little bit. But you know, as I really do enjoy giving these talks, because when I first meet a myeloma patient for that first visit, I do have a lot of time to talk to them about big picture. But in 15 minutes subsequent visits, we really have to focus on the care. So this really gives us an opportunity to talk about the things that I wish I had time to talk about my patients with. So as I kind of go through these slides, these are the things that my patients asked me and the things that, you know, again, I wish I had more time to dive into. So and as Dr. Patel highlighted, you know, no two myeloma patients are the same. So I think as you're starting your journey and your treatment with myeloma, it's really important to talk to your doctor about your specific disease and your specific setting. So you want to be asking some of the things that we've already talked about. So you know, what is my what are my disease burden look like? What does my imaging look like? What are the genomics in my bone marrow? What do we at least know from the tests that we've done? So even though we are not great at predicting risk, unfortunately, we're okay. But we do know a fair amount of things, at least when you show up for that first visit that dictate outcomes, and it's more than just the disease that Dr. Patel highlighted. So what is my social support? What's my ability to come to treatments? Unfortunately, these are barriers to good care, but also to enrollment on clinical trials, for example. So these are important things to ask your doctor. And if you don't get through it all in your first visit, you know, these are things that can be tackled in subsequent visits. Next slide. So when I think about myeloma, this is a three step process. So it's a chronic disease, unfortunately, as of now, although as Dr. Gertz highlighted, you know, we all have patients in our clinic that are 20 plus years out and have never relapsed. And I wish that was everybody, but it's not for most of our patients. So the first step is what we call induction. So we're trying to induce or get our patients into a pretty good remission, get rid of a lot of the weeds in the garden, for example. And even in elderly frail patients, we have great treatment options. So we've come a long way in this space. Next. And then, oh, my arrow is off. That's okay. So the next is what we call consolidation. And this is where transplant comes in. Again, we've gotten our disease into a pretty good remission, but how can we get rid of a lot more of that cancer in the bone marrow? And transplant is, in my opinion, in many is the best option to do this. But consolidation can also be non-transplant approaches, just continuing further on the therapy you started with. And then next. And then I would just say, and this has been highlighted, excuse me, you know, everybody's a transplant candidate until they're not. So I would encourage you and if you all know others who have myeloma, everybody should at least be evaluated in a transplant center, both for that option, but as well as potentially clinical trials. And also, you know, we're more than willing to work with your community physicians to help them develop the best plan for you. And so then the final part of this three-step process is the maintenance. So this is a chronic disease. Once you get your disease into a good remission, get rid of most of that cancer in the bone marrow, you need typically some low intensity therapy to keep your immune system engaged against the cancer. Most commonly, that's a drug called Revomib, but there are a lot of other options. Next slide. So I'm going to talk more about step two, consolidation. That's the transplant. Next. So I think there are about 40 different acronyms for a stem cell transplant in myeloma, so don't get confused. You're going to hear a lot of these things, autotransplant, autologous stem cell transplant, bone marrow transplant, stem cell rescue. We're all referring to the utilization of your stem cells to treat myeloma more aggressively with a drug called melphelin that I'll come to in a minute. So stem cell transplant is really not about the stem cells. The stem cells are really a mechanism to treat your cancer more aggressively. There is a great drug called melphelin, and this is chemotherapy. This is not like our new myeloma therapies. So this drug has a lot of side effects, potentially. And what limits our ability to give it outside of a transplant is how it beats up the bone marrow. And there are some other side effects, too, and we still do use some oral melphelin in myeloma, but not as much as we used to. And so we first used melphelin back in 1958, and ultimately the dose limiting, you can think about it as a side effect, but restriction of melphelin is how it beats up the bone marrow. So what we do, we collect your stem cells first, that allows us to put them like we talked about in the freezer, so to speak, and then deliver much higher doses of chemotherapy melphelin to treat your cancer. But ultimately, it's all about the melphelin. Next slide. Finally, transplant is not risky. If you come into our clinic, we're going to do a pretty thorough assessment to make sure you're a good candidate, meaning you don't have medical problems that might prohibit you from getting a transplant. But we will transplant patients on dialysis, we'll transplant patients with a fair amount of medical problems. Again, it's not right for everybody, but I would say, kind of anecdotally, most of the patients who end up in my clinic who don't get a transplant, frequently it's for social reasons, not medical reasons. So again, see your physician, know that transplant is always a good option for most of us. Next slide. Next, next, next. Good, I was going to go to those individually. But this is the process. So step one is you come in for a transplant, you're decided that it's right for you, we stimulate your bone marrow, we give you some shots to make you make more stem cells. We then collect those stem cells, like Dr. Gertz said, and they ultimately go into the freezer. After that, we bring you into the hospital, that's where you get the chemotherapy drug melphelin. And then two days later, in the final step, we give you back your stem cells. So again, why how I describe this to my patients is this really is a vehicle to treat the cancer more aggressively. There is no immune effects to a stem cell transplant, they're your stem cells. So it's a gift you're giving yourself that ultimately allows you to get into deeper remissions. Next. So what's the role of transplant today? Next. So we're still doing a lot of them. This is data from the CIBMTR over time. And what you see going back to the year 2000, all the way up to 2020, the numbers just keep going up, because we've learned how to do these safer. We've demonstrated over time that it is probably the best option for all patients with myeloma. Excellent. And what this shows is over that same time period. So the top that light blue dot is the most recent time period. The dark blue line on the bottom is the oldest data. So going back to 2001, is that survivals are improving after transplant over time. So this has a lot to do with the therapy before and after the transplant. But it again, it shows that transplant is safe, and it shows that it leads to the best outcomes. Next slide. Next. Keep going. Keep going. And stop there. So we've looked at transplant compared to other myeloma therapy over and over and over again. First, we compared it to kind of chemotherapy. So some of our older drugs, drugs like Melflin. Then we compared it to kind of our modern myeloma, three drug combinations. So frequently utilized regimen was something called Cyborg D. And then we kind of compared it to our superior modern regimens. So RVD, you might hear about that in your clinics or maybe we were even treated with that. And then finally, I'll talk about this most recent study, the Fortase trial that compared it to something called KRD. So KRD is a drug called carfilizomib, a newer version of vortizomib or Velcade. And what we keep learning over and over again is that if you're eligible for transplant, the transplant is producing the longest remission. So again, something you want to talk to your physician about and make sure that it's an option for you. And if not, understand that. Next slide. And so what is insanity? It's doing the same thing over and over again and expecting different results. So I think unfortunately that's what we've done, but these have been important questions in the field to make sure that we're giving patients the best outcomes. Next slide. So I just want to spend a minute on this study, because this really was a big European study that was recently published. In this study compared a couple of different treatment options when you're first diagnosed, but importantly, a regimen called KRD that you see there on the top, arm B, or excuse me, it's on the top and the bottom on the left, on engaging your immune system to kill the cancer for you. So again, this is an important step. And then one more, I think. So what's the next step? Unfortunately, if you have a higher risk type of myeloma, this maintenance isn't as impactful for you. So what we're trying to look at now is does everybody need maintenance? Meaning if you're one of those patients who's in a great situation with their bone marrow, we can't find any cancer, you might not need any more therapy. So we're starting to look at that in some clinical trials. And then on the other end of that spectrum, if you're a higher risk patient, you probably need more than just that Revlimid pill. So ideally, you should be on a clinical trial, in my opinion, if you're a high risk patient. But again, that's why understanding your risk is critical at diagnosis, to make that first treatment decision, to talk about the benefit of transplant, and then to create the best care for you after your transplant. So again, we have a lot more work to do. And there's a lot of exciting studies that are going on right now that are going to start to answer some of these questions. The next slide. So this was I was also asked to talk about, if can I get a transplant if I relapse, or my myeloma comes back? I think this is a really difficult question to answer. When we did the first studies looking at the benefit of transplant, and even the more more recent ones, the studies were generally designed where if your cells were collected, and you didn't get a transplant, the concept was when it comes back, you could get the transplant later. Was anybody knows life changes, and social support changes, and your ability to get a transplant may be different later on in your disease than it was when you're diagnosed. So unfortunately, when we collect stem cells, and we don't do that transplant in the beginning, I would tell you frequently, unfortunately, it never happens. So, so although it is an option, and I think it's still a great option, if your myeloma relapses, and you are a good candidate, again, you have good social support, you're strong enough to get through a transplant, it's never our first choice. And we will also occasionally, although this is getting more rare now with better drugs, use a transplant as kind of a salvage therapy, meaning something to kind of try to get the myeloma under better control for a while, while we can maybe get you on to a clinical trial, or some of our newer therapies, but that is being utilized much, much less. So I can't stop, we can actually go forward, forward. One more, one more, stop there. Yeah. So I really enjoy treating myeloma because I have to be a good internist. So in order to a good general medicine practitioner, because in order to effectively treat myeloma, it's not just the drugs that treat the cancer. It's all this additional supportive care that is critical to making your journey as smooth as possible and preventing some of the many, you know, really shattering side effects that this disease can cause. So it's critical that you're on a calcium and vitamin D supplement to strengthen your bones. It's critical that as part of your initial treatment, you're on some therapies to also build up good bone health, because eventually one day your myeloma probably is going to come back and you want those bones to be strong, and you want to be in this best of a chance to get the best therapies that are available to you in the future. You typically need to be on some sort of an aspirin or a low dose blood thinner, because most of our drugs, unfortunately, increase the risk of blood clots. You need to be on other preventative medications to reduce the risk of infection. The number one cause of death for myeloma patients remains infections. So a drug called Acyclovir, critically important to reduce infection risk. Other drugs you might hear about, back germ or antibiotics at certain times in your journey, also very important. Vaccines, vaccines, vaccines, vaccines, vaccines. So there's so much talk about COVID. It's very important. But there are other infections that we see more often than COVID. Pneumonia, shingles. Anybody who knows someone who's got neuropathy after shingles, it's a horrible journey. So as you start your myeloma care, these are really critical things to, again, maximize your chance of not just controlling the disease, but having the best quality of life along the way. And then finally, something that I probably should have put at the top, but psychiatric and psychological support. So anybody that comes to our cancer center that's being evaluated for a transplant, they are mandated to see our psychologists. And frequently, they don't need a lot of support, but frequently a lot of support they probably could have been benefiting from the whole way shows up at the time of transplant. So it's important that you're offered that potential and that support. And I would really encourage patients to utilize it. Next slide. And I think that's all I had and I have 20 seconds. So thank you. And if you have any questions, I'm more than willing to answer them later.