(Guest Lecture): How to Determine Whether or Not a SCT is Successful

a stem cell transplant is successful. The reason why we wanted to talk to you about this is because many patients understandably experience intense frustration when their stem cell transplant does not put them into full remission, and others feel real disappointment when they don't achieve MRD negativity. It might even be something that someone is on the fence about a stem cell transplant because they're not sure what the outcome will be. Here today we have Dr. Trico to share his thoughts on what constitutes a stem cell transplant procedure as successful or unsuccessful and whether or not it's worth the risk of having it not work, perchance. It's my pleasure to introduce him to you, Dr. Trico's most recent clinical style studies, excuse me, focus on not only attacking myeloma cells but also the microenvironment that supports the survival and growth of myeloma cells. His work aims at finding treatments that are non-cross resistant with current chemotherapy and therefore can eradicate the drug resistant myeloma cells. His work on detailed genetics of myeloma cells should allow individualized therapies to ensure the greatest efficacy while minimizing toxicity. Over the past several years that he has been in practice, the median survival for patients newly diagnosed with myeloma has in large part due to this work increased from only 2.5 years to more than 10. The complete remission rate has increased from 5% to 80% and one third of all patients are still in complete remission at 10 years. This is so hopeful and I'm so grateful for the work that you've been doing and how exciting to see this progress, Dr. Trico. He received his medical degree from Catholic University in Leuven and has been in practice for more than 30 years. We're so excited to hear from you today. Thank you again, Dr. Trico, for being here. I'll pull up your slides now. Thank you very much for this nice introduction. All right, are you able to see those? Yes, thank you. Okay, perfect. Let's go to the first, the second slide. Okay. And when we see a patient that's newly diagnosed with multiple myeloma and we look at bone marrows, we can see the plasma cells. Unfortunately, as you can see in this slide here, when you see patient X and patient Y, their plasma cells look exactly the same. However, patient X relapses after 18 months and patient Y is still in remission at 10 years. So morphology, looking at the microscope and at the myeloma cells is not the answer to identify patients who are at high risk versus those who are at lower risk. Next slide. One of the first things we identified in the early 1990s is that there are tremendous genetic abnormalities in myeloma. And this is a pain karyotype. And we're supposed to have two chromosomes, two copies of each chromosome, as you can see here in chromosome two, the second one on the top, supposed to be two the same and is supposed to have the same color. But as you can see in chromosome one, there are three copies of those. Chromosome nine, there are four copies of those. And then there are other chromosomes like chromosome 13 and chromosome 17. And there's only one copy of those. In addition to that, there are translocations, meaning that there is exchange of genetic material from one chromosome to another. If we look at chromosome 11, the third copy of chromosome 11, you see a little yellow dot on there. And if you go back to chromosome, and that comes from chromosome one, and if you go back to chromosome one, you see a little yellow dot on there. And if you go back to chromosome one, you can see that there is a blue dot on top of it. And that comes from chromosome 11. So part of chromosome one is on chromosome 11 and part of chromosome 11 is on chromosome one. So there are multiple changes on average. There are at least 11 abnormalities in an average myeloma karyotype. So we know that because of those genetic changes and the tremendous amount of genetic changes, that genes were going to be important in myeloma. Next slide. And how can we assess whether the patient has low risk or high risk? This is the assessment by the Mayo Clinic, presented by Dispensieri in 2016. And patients who have a low stage in ISS1, low tumor load, ISS2 is an intermediate tumor load, ISS3 is a high tumor load. If you have a low tumor load, but you have high risk FISH, and high risk FISH means that you look at the chromosomes and there is an abnormality of either chromosome 17, where part of it is missing on the short arm, where the p53 genus, or you have an 11, sorry, you have a 414 translocation or a 1416 or a 1420 translocation, then you're high risk. Also, if you have additional copies of chromosome 1q, you're at high risk. If you have a stage 2 disease, ISS stage 2 or 3 disease, and you have high risk chromosomal abnormalities as detected by FISH, you have high risk disease. Next slide. But better than FISH analysis is gene expression profiling, as we started to do in the early 2000s. You can see this is on our total therapy 2 protocol, and you see the patients alive, the patients with low risk disease are in green, the patients with high risk disease are in red, and for those who are not very familiar, when you start your treatments, 100% of the patients are alive, and then you go out in time, and then you can see that patients are dropping off and dying. But you can see that patients who have low risk disease do tremendously better than patients who have high risk disease. For example, here in total therapy 2, at five years, you can see that two-thirds of those patients are still alive, while in patients who have high risk disease, only a third of those patients are still alive at five years. Next slide. And to show you how important that the gene expression profiling is, let's go back to stage, to ISF stage 1, which is supposed to be a low tumor load, and is supposed to have a good outcome. You can see that patients who have low risk disease in blue have an overall survival that is clearly superior to patients who have high risk disease and are in the red color. A second important factor, but not as important as genetics, is how extensive is the myeloma, and that is best defined by MRI or PET scan. You can see that patients who have 0 to 4 MRI lesions in this slide here do a lot better than patients who have 5 to 20 lesions or who have more than 21 or more lesions. The survival is clearly better if you have a lower tumor load. So the two most important prognostic factors in myeloma are the genetics, either measured by FISH or gene expression profiling, preferentially by gene expression profiling, and the extent of the disease, preferentially by MRI or PET CT scan. And you really need to have information about your genetics and the extent of the disease by MRI or PET scan before you start any type of treatment, because afterwards you can never go back and decide, am I high risk or low risk or whatever. You need to have that information. If your doctor doesn't give you that information or doesn't do those tests, you're probably not in very good hands. Next slide. So our treatment approach has always been to perform tandem transplants and to give all the potential treatments that are effective up front, not to hold back and say, well, if patients relapsed and I don't have anything anymore, our goal was to cure. And if you want to cure, you need to have all the tools available up front in the treatment. Total therapy one was started in 1989 and was before we had any bortezomib or any thalidomide. Total therapy two was a randomized study where half of the patients received intensive treatment plus thalidomide and the other half intensive treatment with no thalidomide. And in total therapy three, we had Felgate available and now patients were receiving Felgate, thalidomide and dexamethasone as a maintenance therapy. That trial started in 2003. Next slide. And you can see that over time, when you compare total therapy one in blue to total therapy two without thalidomide in red to total therapy two with thalidomide in green and total therapy three with thalidomide in green and total therapy three with thalidomide and that the results clearly improved. And you can see the overall survival on the left side and you can see the amount of years. This is not months. This is actually years. And you can see that 60% of those patients are still alive at 10 years. And when you go to the right part of the slide, you see the progression free survival, meaning those patients have not shown any sign of relapse. At 10 years, still half of those patients have not progressed at all. Next slide. It used to be that the 414 was a very poor prognosis myeloma, but as you can see here, if you compare on the left side, total therapy two without thalidomide in green to total therapy two with thalidomide and total therapy three in blue, total therapy two with thalidomide in green. Total therapy two with thalidomide in red. You can see that there's clearly a much better outcome for patients in total therapy three, but basically their outcome is very similar to patients who did not have this poor prognostic marker. Next slide. You can also see here that even in total therapy three and total therapy three here is in blue and in green, you can see that total therapy three therapy was able to provide a similar survival as patients who did not have the 17P abnormalities, provided that the patients had low risk gene expression profiling. Here you see the outcomes, progression free survival by protocol and risk factors, and it's very easy to see that if you have low risk disease on the left, that those patients, especially with the combination of felfate and thalidomide as in total therapy three, do much better than patients who have high risk disease. High risk disease is still a tremendous problem for us, and you can see that most of those patients will have relapsed within the first three years. However, there's still a proportion of those patients, about 20%, that is still in complete remission at 10 years. And it's very, we cannot distinguish between the 20% that will do extremely well in spite of having a high risk disease, and the 80% that will not do well with high risk disease. Next slide. People always think that they have to achieve a complete remission and that they have to be MRT negative to have a long survival, but as you can see on this slide, this is certainly the case in high risk myeloma. But high risk myeloma is only 13% of all the cases. Low risk myeloma is 87%. You can see that whether you achieved a stringent complete remission or not, that was not that important for overall survival and actually was not even significant for those patients. So while it's extremely important for patients to achieve MRT negativity and to achieve a stringent complete remission when you have high risk disease, it is not that important for patients who have low risk disease. And patients with low risk disease, especially those who have 11-14 translocation and are CD20 positive, many of those patients never achieve MRT negativity and never achieve complete remission, but nevertheless do very well. And when we look back at our total therapy one protocol, which was the first one, which started in 1989, when we looked at patients who were still in remission more than 20 years out, and that was a total of 24 patients, 13 of those patients had never achieved a complete remission. 11 had achieved a complete remission and never relapsed, but 13 never achieved a complete remission and were still progression free at more than 20 years. Next slide. So based on all those treatments, even the Mayo Clinic presented in 2016 that patients who have intermediate risk and patients who have high risk disease should have tandemontologist transplants and should be maintained with proteosome inhibitors and thalidomide. In their opinion, patients with standard risk only needed one transplant. I think that's still not the right thing to do because those are the patients who have the highest probability of doing extremely well with intensive treatment and being cured of their disease. Next slide. Here you see the impact of MRD on outcome, and you can see there is no doubt that in general, patients who have MRD negativity do much better, they are in red, than patients who will remain MRD positive. But again, there are clearly exceptions, and especially in the 11-14 translocation, it's not uncommon to remain MRD positive and to still have an extra outcome. Next slide. And this slide summarizes how we view treatment. When patients are diagnosed, they have about 10 to the 12th to 10 to the 13th myeloma cells. If you treat them with conventional chemotherapy, even with the newer drugs, but no transplantation, as you can see, you go down to the 13th myeloma cell, and you see that the patient is still in the you go down just a little bit. That's the upper curve, and very quickly you will see a relapse. If you do a single transplant, which is a second curve, a little lower than the first one, you can see that those patients have a better reduction of their tumor load, but still all relapse. If you do two transplants, but you don't maintain them well, then most of those patients will still relapse, although you still see a better tumor reduction overall, and the time to relapse will certainly be longer. It's a combination of tandem transplants with maiden therapy with Velcade, thalidomide, or other IMIT for at least two years that can lead to clonal extinction and cure, and where you can really see patients having no evidence of relapse 20 years after they started their treatment. Next slide. And here you can see the progression we have made since we started this treatment in 1990, where conventional chemotherapy gives you about two and a half years of survival. Conventional therapy with new drugs, four years. A single autologous transplant, about five years of survival. Tandem autologous transplants, about seven years of survival. A single transplant with the newer drugs, if they are combined, an IMIT with a proteosome inhibitor, probably approximately eight years, although those data are not very hard and there are not a lot of studies showing that. But if you do tandem transplants and you use the newer drugs as maintenance therapy, your median survival is going to be in excess of 12 years, with a third of those patients still alive and doing well at 15 years. I think that was the last slide. And we can now, you know, let me, you know, this is a summary of the findings that autologous transplantation remains the preferred therapy for transplant-eligible patients, and most patients are eligible for transplantation. The major cause of death is failure of treatment and not treatment related to mortality. Patients think that intensive treatment may be too taxing on them and that they may die from all these intensive treatments, and some do, but that is a very, very low percentage. Most people fail because their disease comes back and they die of their disease. Prolonged survival can only be achieved in a large fraction of patients by combining all effective agents up front and not holding back for relapse. Achieving a stringent complete remission of MRD negativity is crucial for patients with high-risk myeloma, as defined by gene expression profiling, but is not that crucial in standard risk myeloma. So, tandem autologous transplants plus consolidation therapy is the key to prolonged remission and survival, where we can now see at least a third of the patients survive 20 years or more and at least half of the patients still being in complete remission at 10 years, and the role of allotransplantation remains still dubious. Thank you. Thank you, Dr. Chikol. That was amazing, and I actually learned quite a bit through your presentation. I really do appreciate you sharing that information with us. It's now your time to enter your questions into the question and answer box that can be found at the bottom of your screen. If you're not seeing it, click our faces and then you'll be able to see it at the bottom. I have a couple questions for you, Dr. Chikol, and I was especially interested about the 11-14 information that you gave us concerning the fact that they don't achieve MRD negativity easily. Is there a study that reflects that, or what can help us find that information to share with others? Well, that's what we found in our... We have done more than a thousand up-front transplants, and it was not uncommon to find 11-14 patients who never achieved a complete remission and still did very well. Although we didn't have that information for total therapy one, my guess is that those 13 patients who were still alive and in complete remission after 20 years were all 11-14 translocations. Interesting. Interesting. Thank you for sharing that. I also have a question about MRD negativity. You said that it's really important for high-risk patients to achieve MRD negativity complete response. I just talked to a different myeloma specialist earlier this week or last week, I guess, and he was talking about MRD negativity can be fleeting, especially in high-risk populations. How do we balance the importance? I agree that there's an importance for MRD negativity, but is it true, in your opinion and what you've seen, is MRD negativity more fleeting in those high-risk populations? Is it less durable? I guess I would ask. The major problem with MRD is the quality of the bone marrow aspirate. If you have mainly peripheral blood, the chances that you will be MRD negative are much higher than if you have a good juicy bone marrow, bone marrow cells. If you have a diluted sample that you use for your MRD measurements, it's not going to be very informative. The second important point is to remember that myeloma is a focal disease, and the focal disease shows up by lytic lesions on the CT scan or by active lesions on PET or on MRI. But you can imagine that if you do your blind bone marrow aspirate in an area where there is a focal cluster of myeloma cells, it's very likely that you will still find some positive cells. If you go outside that cluster in an area that looks totally normal, you might think, oh, it's all good. There's absolutely no myeloma cell anymore. My MRD is totally negative. One needs to see that in context. Leukemia is much easier. It's the same everywhere. It's spread out everywhere. It's easy for them to say, well, this patient is MRD negative and will do well. For myeloma, because it's so focal and because myeloma cells tend to form big clumps and big clusters, it's much more difficult because you don't know if you do a blind biopsy whether you're actually in an area that has lots of disease or in an area that looks totally normal. That helps the point of not focusing too much on whether or not you achieve MRD and negativity because those answers can be so different depending on where you tested. That's a good point. Anita is asking a great question. She said before her stem cell transplant, she was high risk, but afterwards they didn't see those three genes that made her high risk. Is she still considered high risk or because those were eradicated, she's not high risk anymore? When you are high risk at diagnosis, you remain high risk. If you do a biopsy or an aspirate after transplantation and you don't find those cells anymore, that means that there are too few abnormal cells left to detect the abnormality. Which is good news, but also... It's not like those genes are gone. No, they're not gone. They're the same. We know that because if patients relapse, they have exactly the same abnormalities that they had at the initial diagnosis. It's not that they now have a totally new set of abnormalities. Is it possible, however, to change genetic risk throughout? Could you change if you were 11-14, could you end up being something else later on? Well, there is. If 11-14 patients develop a 17P deletion, a P53 deletion, or if they acquire multiple copies of one cube, it's clear that their risk increases. If you do fish and they stay with the 11-14 only and nothing else, then they remain good risk. It's like you were saying at the beginning, genetics make this a lot more complicated. A lot more complicated. Let's talk about tandem transplants. Does it mean tandem when it's only within one year of each, or when it's one year apart from each other, when it's within one year? Could it be considered tandem if it's three or five years apart? What's the definition of tandem transplant? Our studies showed that the best results are found if you can do the two transplants within six months. There's clearly a lot of benefit if you can do it within the first year, but if you do it more than year apart, you have no benefit from your second transplant. If somebody is interested in doing tandem transplant, they should get it done within six months, at the most one year. It's best within six months. It is an option, however, if I understand correctly, to have another stem cell transplant later on in the road if you do relapse. Is that true? That is true. It's true and it's not true, but it's true in most cases. It depends upon how long your first remission was. If you do a single stem cell transplant and you relapse within six months, another transplant is not going to help you. The first transplant could not get you farther than six months. It's not going to help you to do a second transplant. However, if you do a single transplant and you stay in remission for seven years, then another transplant is certainly a good option. The longer the time to relapse, the more likely it is that you will benefit again from another transplant. Interesting. Thank you. Judith is wondering, would you do fish testing with every bone marrow? Yes. Okay. Gerarda is wondering, she's been in remission and her doctor does not want to do a stem cell transplant now. He said later. She has high risk genetics and worried that if she doesn't do transplant that her remission will be short. She is on maintenance. What is your opinion, not necessarily in this specific case, but in general on this kind of situation? The first thing I would like to know is, is this patient in a stringent complete remission, meaning that the light chains are normal, and is this patient MRD negative? If they are not in a stringent complete remission and if they are not MRD negative, it's only a matter of time before this patient will relapse. If the patient is in a stringent complete remission and and is MRD negative, then one could make the point that maybe we can wait a little, do bone marrows every three months, and as long as the MRD stays negative and we are in a stringent complete remission, we can wait. It would not be my preferred treatment, but I would totally understand that people do that. Okay. Thank you for explaining that. Maria is wondering what is meant by MGUS-like disease? We are told that as well. My husband's condition seems to be after his auto transplant. He has standard risk. Yes. So MGUS, as you know, comes before myeloma. It's an early stage where basically there is no increase in the tumor markers. There is no evidence of any organ dysfunction, and it all looks good. People have a normal spike when they do their blood tests and have some increased plasma cells in the bone marrow, but they don't do any harm to anybody. So there are some patients, and again, that's where the 11-14 comes in again, where we don't achieve a complete remission, but those patients stay with their minimal disease, a little bit increased number of plasma cells, still a little spike on the electrophoresis, and they stay stable for years and years and years and years. So we call that an MGUS-like state. Okay. These patients behave like MGUS, not like myeloma, and the risk of those patients going to myeloma is 1% per year. After 20 years, it's still only one in five who will have relapsed. Wow. Okay. Couple questions coming in. So in this patient's case, stem cell transplant didn't achieve remission, still MRD positive, and what are the chances that another stem cell transplant would be tried? Looks like they're in a clinical study utilizing deritumum, avum, and Revlimid. I'm a little confused by that question, but I think if the person is in this, if they've had a stem cell transplant and they remain MRD positive, would you recommend doing another stem cell transplant to make them tandem? Again, the first thing I would like to know is what are the genetic features and what is the extent of the disease. If people have extensive disease to begin with or have high-risk cytogenetics, I would certainly do a second transplant without any doubt. If people have very low-risk disease and have an 11-14 translocation, I might be less inclined to do a second transplant. Okay. And I think this shows the importance of two things. One is giving second opinions if you're not comfortable with what your specialist or your oncologist is saying, seeking a second opinion, having a different specialist look at labs, and making a decision together in that way. And also, I see several of you that are unsure what your FISH results say or what your translocations are and if you're high-risk or standard risk. That's something that I would call your clinic, your treating clinic immediately, and ask. There's more power in knowing and being aware of what your disease really looks like, especially if you're newly diagnosed. So that would be my recommendation. Do you have anything to add to that, Dr. Trichot? Yes, it's important that people with myeloma understand that there is potential for cure and that you can only cure myeloma if you treat it well up front. That with every time the disease comes back, you have made myeloma cells smarter and smarter. And you select, you have eradicated the dumb cells and you select for the smart cells. You do that more and more with every relapse. And in the end, nothing is going to work anymore because your myeloma cells have become way too smart. They outsmart every type of treatment. That's why you need to give intensive treatment up front when the myeloma cells are still naive and have absolutely no clue what's coming to that. Yeah, that's interesting. I appreciate that insight. Eddie is saying that he has 414 location and is a recipient of a tandem transplant. He feels pretty good, but is wondering how does he know if he is in remission? Well, the only ways to know that is by doing MRD testing and by doing bone marrow and by doing PET scans. If the PET scan still lights up in several places, they are not in remission. If the bone marrow is negative, it just did a bone marrow in an area where there's nothing left, but there's still other places where there is disease. So all those tests, MRI, PET scan, bone marrows need to be repeated on a regular basis. And you need to have all the pieces of the puzzle together to say, this is it. And if you start to not to perform certain tests, you start to guess, you start to shoot in the dark. And that's usually not a good thing to do. Especially myeloma. So Eddie, I would echo what Dr. Truco said. Please get tests. I also just wonder how long it's been since your tandem transplant. I'm sure those tests are coming if it hasn't been very long. And I know that you're worried about the 414 translocation, but especially working with a myeloma specialist, they can get you those treatments that are going to be most powerful that can work for you, like Dr. Truco said. So hopefully. The other important thing is if you do really close follow up, like we used to do every three months, even if the patient would relapse, you're going to find the relapse in a very early stage, not when they break bones or have massive disease. And it's always much easier to eradicate or control little disease compared to lots of disease. Yeah, definitely. We have several newly diagnosed patients on today, which I'm very excited about. Penny is wondering if the MRD test is a blood test. So can you briefly explain what the MRD test is? So the MRD test is a test that's done on the bone marrow, where you take a bone marrow aspirate and you have decided either by doing gene sequencing or by flow cytometry what the abnormalities are. And then you look at the plasma cells that are remaining and then you see whether you can find those original abnormalities again. If you can find them, your MRD positive. If you cannot find them, your MRD negative. So it's always on the bone marrow. And I know it's not comfortable to have a bone marrow, but it's extremely important, especially in high risk disease to do those tests on a regular basis. Yeah. And we actually have a recording about MRD, what it is, and we can send out in our resources email that we send out within 48 hours. So I'll make sure to include that. Cindy asks a good question revolving around maintenance therapy, which we briefly touched on. Would you recommend, I'll summarize her question here, but would you recommend maintenance therapy for everybody or only those who are high risk if they are MRD, these are for MRD negative patients? I would recommend a combination maintenance therapy with an image and approach to so many better in everybody for at least two years. Regardless of MRD to negativity or not? Doesn't matter. It doesn't matter. Because of the the slide that showed the different exactly. Exactly. Yeah. And again, there are limitations to MRD testing as we discussed in the beginning. You might be in a good area and think, oh, everything is fine. Yeah. Yeah. Yeah. Thank you. Steve is wondering, do you think that a second or third opinion should be found from a totally different multiple myeloma center? I'll answer that one if you don't mind and then if you have any opinions. But I think it really depends on insurance. The harsh reality of US insurance is sometimes they don't cover certain centers or certain areas. So that would be something to consider before getting a different opinion in a different area. But but we we just we recommend second opinions and you can decide based on your personal experience what that looks like and where that looks like. I would like to add something to that. It always amazes me when I was seeing patients that they spent more time on trying to find their next car than trying to find the best treatment option. And this is a life threatening disease and curable. So you really need to spend time. And in myeloma, it's very uncommon unless you have renal failure due to your myeloma that you are in a hurry to start treatment. You have the time to get a second opinion. And it's very important. Once somebody screws up the initial treatment, it's very difficult to write it again afterwards. You really need to feel comfortable and you really need to be in charge of your treatment. You need to feel that this is what I want. And you can only know that if you read a lot and you listen and you go to support groups and things like that. Yeah, yeah, exactly. Thank you. I echo your words. One more question. Steve's wondering, so we looked at those charts and those overall survival graphs and saw that several patients were passing away. Did that indicate that they were passing away from multiple myeloma or could it have been other causes that caused their death due to comorbidity? There could have been other causes, but our experience tells us that 90 plus percent die of the myeloma. Okay, awesome. Thank you. Well, I know that you have an important meeting to get to, Dr. Trico, so we will end a little bit early today, but we really do appreciate the questions that were asked, the participation, and I'll finish up with some outro announcements. Thank you again, Dr. Trico, for joining us today. We really appreciate you. You're welcome. So you can join us next month in the stem cell transplant chapter. We're going to be talking about the importance of walking and fitness during and post stem cell transplant. That's on April 7th at 1 p.m. Eastern, and we'll announce the speaker here shortly once we work out those details. I also wanted to let you know about the health tree moves for myeloma March fitness challenge. So many of you know about the move springer, muscles for the legs, and the leg muscles. We're going to be talking about the move springer, muscles for myeloma fitness challenge that we do every month to celebrate myeloma awareness month. We've changed our name recently to be health tree moves for myeloma, and we're really excited to get started with this challenge. Our commitment is to become more active by 20 minutes of activity per day, and we have a team goal of 600,000 minutes for the whole month. You're welcome to join us. There's a register link on here. You can find the health tree moves app in Apple app stores. Unfortunately, right now we're still getting it up for Android users on the Google Play Store. Our team is working diligently on that, but we would love for you to join us. You can sync your Apple watch, your Fitbit, or even just manually record your activity so that we can focus on a month of fitness together in order to commemorate myeloma awareness month. We're really looking forward to that, and these slides will be sent out to you, so you can look up that link if you would like that. You may be interested in other myeloma crowd community events we have coming up. On the eighth, we have two separate events. The first one is the non-secretory. It says Pacific time. It's actually Eastern time, so I'll make sure to get that corrected before we send it out. At 1 p.m. Eastern time on the eighth is our non-secretory myeloma patients chapter. We're going to be having a guided discussion sharing what tests are used to measure your non-secretory myeloma. This group is all about sharing experiences, sharing information so that we can further research in this field together. On the eighth at 6 p.m., that is Pacific time because it's a regional chapter, our SoCal myeloma community chapter. We're going to be hearing from Dr. Caitlin Costello, who's going to be talking about hope, action, and evolving myeloma research. Dr. Costello is at UCSD at the Morris Cancer Center. The ninth, we also have two different events. One of them is the Health Tree Moves for Myeloma event. That's going to be at 7 p.m. Eastern. Earlier that day, we're going to hear from Dr. Nathan Sweeney. He has a PhD in research, and he's the head of research here at the Health Tree Foundation. He's going to be talking to us about furthering myeloma research and search for a cure. What studies have we done recently? What surveys have we done? What can you participate in to further a cure? And what are we learning about what a myeloma cure means to the myeloma community? Does that mean that it's disease that you have but you don't die from, or does it mean that you completely eradicate your disease? People have different opinions on this, specialists and patients alike. So we're going to join together to talk about this and further myeloma research together because that is how we can get closer to a cure. We can't do it without you. The link to sign up for any of these events and even more events that I have not mentioned is found at the bottom of the slide and will be sent out in that follow-up email that I have been referencing. As always, I'd like to thank our sponsors, without whom this would not have been possible. Bristol Myers Squibb, Amgen Oncology, Genentech, Adaptive Biotechnology, Xanafee, Janssen Oncology, Karyo Pharm Therapeutics, Takeda Oncology, and Abbe. I see a couple questions about if this recording will be sent out. Yes, it will to all registrants. You will receive the recording so you can watch again. And thank you. Thank you so much for being here, helping us build a strong myeloma crowd community. I appreciate each of you. Hope that you have a great rest of your day. Thank you so much. Bye-bye.