(Guest Lecture): February 2024 - Hope for the Future in Black Myeloma- A Black Myeloma Health Panel

Our goal is for you to learn how immunotherapies are or could be used in each stage of myeloma, as well as what other novel therapies are available and how Black patients can benefit and take full advantage of them. Now our speakers today, Dr. Monique Hartley-Brown, is an emerging leader in the field of multiple myeloma. She's an associate physician at Harvard Medical School, an assistant professor and medical oncologist who specializes in treating patients with multiple myeloma. She practices clinical care at the Jerome Leipa Multiple Myeloma Center at Dana-Farber Cancer Institute. Multiple myeloma is an incurable cancer that affects Black Americans approximately twice more than Caucasian. Dr. Hartley-Brown has written several publications and has been a clinical research investigator numerous clinical trials that has contributed to the advancement of clinical care for patients with multiple myeloma and plasma cell dyscrasias. As a Black female physician, she is dedicated to ensuring that the care for a multiple myeloma community is equitable and affords all patients and myeloma an optimal level of care regardless of background, race, or socioeconomic status. Dr. Raleigh Fatoki is a hematologist oncology fellow at the University of Miami Sylvester Comprehensive Cancer Center. His research interests include multiple myeloma and the biological drivers of disparities in people of African descent. Dr. Fatoki studied economics at Howard University before completing a joint MD MBA program at Meharan Medical College and Vanderbilt University Owen Graduate School of Management. He trained in internal medicine with Kaiser Permanente in Oakland, California. Dr. Brandon Blue is an assistant professor at the Moffitt Cancer Center in Tampa, Florida. His clinical interests include the treatment of plasma cell disorders and the evaluation of patients pre and post bone marrow transplant. His research interests include reducing health disparities and improving health outcomes of plasma cell dyscrasias. Dr. Blue recently completed a blood and bone marrow transplant and cellular immunotherapy fellowship at the Moffitt Cancer Institute. Now as we go along today, please feel free to write your questions in the chat and we'll address them as we go and there also be ample time for Q&A. So without further ado, I want to introduce you to Dr. Monique Hartley-Brown who's going to be presenting information on MGUS and smoldering multiple myeloma. Dr. Hartley-Brown, the floor is yours. Thanks, Valerie, and thank you so much for that wonderful introduction. I wish there was somebody to introduce you because you brought us all together and you've been doing a phenomenal job in educating other patients with multiple myeloma. So for now, I'm just going to share my screen and see if we can move forward with this topic. My job today is to give a little bit of an overview of monoclonal gliomopathy of undetermined significance, another word for MGUS, and smoldering multiple myeloma. And it's not moving. There we go. And so just as an overview, multiple myeloma, as you all know, is a cancer of plasma cells. It's a blood cancer. It's the second most common type of hematologic malignancy. And those blood cells are those plasma cells are the cells that become the myeloma cells. They live in the bone marrow. Their normal function is typically to make antibodies to attack and kill germs. However, when they become cancer cells, I like to use the picture of the turtle and the mutant ninja turtle. So when they become mutant or cancerous, they start doing things that they should not be doing, which is one, multiplying out of control. So they themselves become larger and they grow more and then they produce proteins that cause havoc. So instead of becoming protectors and killing germs and attacking germs in your body, it actually attacks the body itself and produces proteins that are inactive in terms of being antibodies in the system. Other things can happen throughout multiple myeloma. The key things are part of what we use for diagnosing this particular disease. And so when we think about multiple myeloma, there are precursor conditions that develop into multiple myeloma. One of them is called M. Gus, which is in the setting of seeing those proteins that the myeloma cells are producing, but at a lower level. And we see about less than three grams per deciliter of that protein, whether it's in the blood or in the in the urine. And then the bone marrow sample, we can see less than 10 percent of those plasma cells. When we look at the body, we don't actually see any damage to any of the organ systems in the body. And the typical things that can happen in active multiple myeloma is you can see calcium elevation because there's damage happening to the bones. You can see kidney problems or as we call renal insufficiency because those proteins can sometimes get caught in the kidneys and cause damage to the kidneys and reduce the kidney function. And you can see anemia where the bone marrow can't function the way it's supposed to because all those malignant plasma cells are crowding out the bone marrow. And as I mentioned before, you'll see bone disease where there's signals from these cancer cells that are telling the body to destroy bone. So in M. Gus, you actually don't see any of those features. But what you do see is there is measurable protein and there is a larger amount of those plasma cells in the bone marrow. Typical bone marrow should have less than five percent. When we move to smoldering myeloma, again, we don't see those features that are causing damage to the body, but we do see the protein that's measurable. And again, it can be three grams per deciliter or greater that's in the blood or the serum. And then you can measure at least 500 milligrams in a 24 hour urine collection of that abnormal protein being present. When we look at the bone marrow, we see plasma cells, but those plasma cells are more than 10 percent and they can be as high as up to 60 percent. And then we again don't see any of these features that we talked about. Active myeloma, there's definitely features of damage. I'm not going to discuss much of that because my colleagues today are going to go further into this discussion of active disease. So some of the risk factors, I get this from patients all the time. Why me? Why did this happen? Some of the risk factors for multiple myeloma and the precursor conditions of MGUS and smoldering myeloma include age. Patients who are older, individuals as they get older, they're more likely to develop cancer. And this is true for multiple myeloma as well. And so we do see an increased prevalence of these precursor conditions of MGUS and smoldering myeloma in patients as they get older. Gender also plays a role. In this particular case, there's a slight predisposition of males having a higher risk of developing multiple myeloma than females and patients who are overweight. So we see more and more that in the Western world, we are finding that individuals are, you know, more and more patients are considered morbidly obese. And that has caused us to find more patients with development of different types of cancers, including multiple myeloma. Family history is key. First degree relative with multiple myeloma or a precursor condition increases your likelihood of potentially having the same condition or something similar. So another condition that may be a plasma cell disorder. And then the most important I consider here is race is important. There are some biological differences that we're seeing. And when we look at Black patients compared to white patients, you see a higher risk of multiple myeloma development, earlier age of development in patients who are of Black descent. So it doesn't matter if you're Black, Hispanic or Caribbean Black or American Black, we're seeing that this increased incidence is prevalent in patients who have African descent. Other malignant conditions and exposures to other things such as Agent Orange. If you think about the World Trade Center exposures, some of those toxins also increase the risk of developing hematologic malignancies and other malignancies like multiple myeloma. And so, as I alluded to earlier, myeloma is more common in Blacks than whites. There's a higher incidence of MGUS and smoldering myeloma, as high as three times more in Black patients compared to whites. And they also present at a younger age. And when we look at the active disease, you're two times as likely to develop active multiple myeloma in Blacks and also, unfortunately, two times more likely to die from multiple myeloma and have a poorer outcome despite the stage of the disease. When we look at monoclonal gammopathy of undetermined significance, we can see there is an increased prevalence of it over the past several years. And this graph, many of the data that we have is a little bit behind the times. But this graph shows that from 2005 compared to 2014, there's a rising risk per year of developing MGUS. But what we also see, if you look at the colors, you can see that the highest incidence is in the Black patients. And then second to that would be the red curve or the red graph. But you see that the lowest graph is in Asians. Some of that may have to do with the fact that there is less of these patients involved in some of the studies that we have. But in general, you can see the incidence in the Black population far more prevalent than in the other populations. So there's a 3% overall population risk of MGUS over the age 50. And then it increases with age over time. And then when you look at the African-Americans or the Black patients, you're seeing that they're three times more likely to have this disease. They're also three times more likely to have a familial component of inheritance. And these are some of the information that I was able to be loaned by a colleague of mine. If you think about multiple myeloma and you think about other cancers, very common cancer, we think about is breast cancer. And there's a lot of ways that we determine early on whether we have a patient that has breast cancer. So we have a screening test. We have the mammogram. And there are all these studies that go into place in terms of trying to detect the cancer early on so you can cure the patient of their disease rather than waiting until they actually have symptoms. Now, if you remember, what I mentioned to you before is active myeloma shows there's already damage to the body. There's damage through anemia. There's damage through kidney problems, bone problems, and high calcium. But we don't have a screening test for this. Despite knowing that there are precursor conditions like M. Gus and smoldering myeloma, we don't have a screening test. And so there is evidence that we could potentially have a screening test for patients who are at high risk. And this is something that is being evaluated by the PROMIS study. And this is an ongoing initiative, a national initiative looking at patients who are potentially at higher risk for developing multiple myeloma or the precursor conditions. And this is because we know that M. Gus is fairly common, especially in certain populations. So if you look at this graph, and this is old data, this is nothing new. We know this. This is, you know, we're talking about almost 20 years old data here. When you look at the lower curve, you see M. Gus, you know, increases your risk of multiple myeloma over time. So 4% to 10% in 10 years to 16% in 15 years to 21% in 20 years. But when you look at smoldering myeloma, there is a much bigger difference. And so early on, those patients who are likely to have active disease, you have about a third of the patients who will potentially have active multiple myeloma at least in 15 years. But you also see that big portion of the curve early on where about 50% of the patients will convert to active myeloma in five years. Those patients are the higher risk smoldering group. And those patients are interesting because we are looking at ways that we could potentially mitigate them from developing or prevent them from developing into active disease. So the PROMIS study has this concept in mind. And the idea is selecting patients who have either fall into the category of either having a first degree relative with active myeloma or fall into that population of patients who may have an increased incidence or increased risk of developing multiple myeloma. And that includes Black patients. And so we know this data already. We talked about this. This is for adults. This is for asymptomatic healthy individuals. Can we identify screening tests, ways to genetically determine patients who might be at risk and somehow prevent them from developing active disease or at least capture them early on with early detection methods? And the testing and all that is funded through the grants received by this process. So there's no cost to the individual who is involved. And this just really, I don't need you to hone in too much on this, but it's to identify clinically and biologically what could potentially be ways that we can target patients from developing or the disease, target the disease rather, and prevent patients from developing active multiple myeloma. Sometimes we get questions from patients. Well, I have a first degree relative who has disease. What can they do to help in this process? And the PEAK crowd study, I just have one slide on it. That's a sister program that also looks at some testing done in patients who have active disease. But for the precursor conditions, those are the things that we really need to see if we can early detection and try to somehow intervene early to prevent progression of myeloma. Other things that I want to mention is, you know, patients of African American descent actually have an increased prevalence of certain genomic differences in their disease. So translocation 1114, this is essentially if you think about your biology, for those of you who are, who recall, as human beings, we have 23 chromosomes from mom, 23 from dad. And so we label them, scientists like numbers. So we label them. So that chromosome 11 and that chromosome 14, they can swap parts. And if they swap parts, that can turn on certain driver mutations that will cause those cancer cells to develop. Same thing for 14 and 16. Now, when you look at the cells, those cancer cells in the Black Americans, they tend to be more likely to have these types of genetic changes in their myeloma cells. And that could be a target. We have treatments. And I mentioned here, Venetoclax, because this is a particular medication that is actually a pill that we are testing in patients with these types of mutations to target this particular change and try to treat the disease. Currently, it's being utilized in active disease. But this is something that is of increasing interest and could potentially be looked at in early precursor conditions. I also want to highlight that all the data I'm presenting today is not new data. We've looked at the seer data. We've looked at mortality in African Americans. We just talked about the genetic changes that are a little bit different. And one of the things I want to highlight is when we also look at some of the patients who are treated in the VA system, so the Veterans Administration system, essentially, they treat their patients the same. And so if a patient comes in and they are evaluated, what they found that within that system, if they're treated the same, the outcomes for Black Americans are actually better. And why is that? Because, again, that translocation 1114 tends to be a more standard type of a risk of myeloma, whereas deletion 17P is a poorer prognostic risk. And we see that a little bit more in the White patients than in the African American patients. Therefore, that discrepancy in outcomes for Black patients does not seem to equate with the genetic changes. They don't seem to have worse disease. So why do we see that? And that is something that I think we need to change and we really need to evaluate and we really need to understand. So we have to look at what are the Black patients being treated with? Are they getting stem cell transplantation? Are they getting these novel therapies that we have? This is an old slide, but if you think about the current therapies, we have some cellular therapies that we're using and I'll get into that in a little bit. But many of the therapies that are offered to their White counterparts are not offered to Black patients. Therefore, the outcomes are less positive. And so I only put this quick slide here just to remind you, because I can't go into too much detail in the interest of time, but smoldering myeloma, just like MGUS, we do have a risk stratification. Again, it is inactive disease, it's considered inactive disease. So we think about patients if they're low risk versus intermediate risk versus high risk. And if you remember that diagram that I showed you earlier, I'll probably try to go back to it, to this here, that high risk is in that beginning with the 50% that's converting to having active disease in the first five years. But as you see, if you look higher up on the graph, the gradient kind of comes down a bit and that gradient starts to look more like the MGUS gradient. And so those patients later on, at the 10-year mark, 15-year mark, those patients tend to be the patients who are behaving in the lower risk category. And those patients have a less likely chance of like around 2% per year of developing active disease. The high risk patients, however, we really need to do something about. And some of the things that we are doing right now at our institution is we're looking at a lot of these novel therapies that treat active myeloma, fully approved for treating active myeloma. And I'm sure my colleagues are going to some of these details later on today. But we're wondering, can we use these therapies in those patients with high risk disease, high risk smoldering myeloma who may potentially develop active disease within a few years? So one example is we have a study looking at daratumumab, a monoclonal antibody, with bortizomib, which is a proteasome inhibitor, and linoleumide and dexamethasone. Linoleumide being an immunomodulatory drug and dexamethasone being a steroid. Now this cocktail of medications is utilized to treat patients with active disease. Here we're using it much earlier. We're trying to treat patients with high risk smoldering myeloma. And we use the criteria. There's a few criteria, but most popular criteria that's used is this 20 to 20 criteria where we look at the serum protein, that M spike we talked about, if it's greater than two grams per deciliter, and or the actual free light chains that we measure in the serum if it's greater, if that ratio is greater than 20 for the active light gene over the inactive light gene. Or if the bone marrow biopsy shows that the plasma cell percentage is greater than 20%, you can fall into that high risk category. And that's an easy thing to look at and calculate. And so these are ways, and we also look at cytogenics and things like that, but these are ways that we're trying to include patients in early clinical trials to try to see if we can prevent the development of an inactive, reportedly inactive disease, smoldering disease from becoming an active disease like multiple myeloma. Another example is we are looking at the depth of response. So we don't continue the treatment forever. Those medications are given for a set period of time, typically about a couple of years. You will be on a maintenance regiment after the initial induction portion of it. And we look at scheduled bone marrow biopsies to see the depth of response. How many of those plasma cells have died? Did we actually get down to one in a million where we cannot find those plasma cells? That's the deepest we can actually measure with our genetic testing. And that's when we consider patients to be MRD negative. If they're MRD positive, meaning we still see some residual signs of these cancer cells in the bone marrow, then we may continue with the maintenance portion of the DERC and the MAB with the linoleumide. If we don't see it in your MRD negative, then typically you wouldn't participate in this part of the study. So the question becomes, what is going to be the outcome of this? I mean, we've had some preliminary data that was presented in 2022. I'm sure we'll have some updates soon, but it would be nice to know what the long-term outcome of this is. We have overall response rates in the 90% range with at least a quarter of the patients getting a complete response. So we really want to see what the MRD negativity status is and what the sustainability of that MRD negative status is over time. So more to come for these patients. And when we think of immunotherapy, sorry, when we think of immunotherapy, we also want to think about in multiple myeloma, whether precursor or active disease, we want to think about reducing the progression of immune stimulation and causing enhanced surveillance. So potentially eradicating the disease early on and then utilizing the T cells. So when we think about cellular therapy, we use T cells to help us. That's part of the immune system. So we want to use those T cells when they're much more active and have not seen other therapies or has not already been trying to fight the disease in the past. So these cellular therapies that we think about by specific antibodies and CAR T cell therapies, I'll go a little bit more into in the next couple of slides, then I'll end at that point. But I'm sure you're going to hear more about it from my colleagues. And again, there we go. So here we go. So by specific therapies, one of which, Toclistumab, which was one of the first by specific therapies that was approved, most of these patients in these trials, or all of these patients actually had active disease, refractory disease. That's typically where we start when we have a first phase one trial in patients. Because we want to see those patients who have exhausted all the treatment options that are approved, we want to see if we can offer them something else that will actually be beneficial and allow them to have a longer survival. And so this particular study utilized Toclistumab, now you see in the drawings here, the protein that the antibody, this antibody is sitting here with the purple side towards the T cell and the orange side towards the myeloma cell, the myeloma cell being in gray. And the protein that's sitting on the surface of the myeloma cell that this product or by specific antibody binds to is BCMA, B cell maturation antigen. On the T cell arm, this purple side, it binds to the T cell through this antigen that sits on the surface of the T cell called CD3. Now, if you just look at this, you don't have to get too complicated. Essentially, this antibody is bringing the immune system, which is a T cell on the one hand, in close proximity to the actual myeloma cell on the other hand, and trying to tell the immune system, hello, be more proactive about killing this cancer cell. Not only is it doing that, but it's also sending direct signals through the BCMA attachment through the cell to cause internal triggers for death of the myeloma cell. So it has all these different ways of working, triggering the immune system internally through direct apoptotic or cellular death mechanisms. And it works very well. In these patients who have exhausted all these therapies, we saw that about almost 40% of the patients were able to get a complete remission. And that was a striking thing. We also saw that over 60% of the patients were able to have a favorable response. And so this was data that kind of blew us out of the water when it came out. And it was very encouraging to know that we had additional therapies that we would be able to offer our patients in the relaxed setting. Now, other bispecifics are approved. In talcuitumab, the protein that is targeted is the GPRC5D protein. That's what sits on the myeloma cells. That's what the antibody binds to on the myeloma cell. The CD3, again, is still on the T cell. Again, here we see overall response rates of over 70%. These are two different doses of the actual product that's being used. And if you look at the information on the chart, it's basically just going through some of the toxins that we see because this is a new medication with a new mode of mechanisms of action. And so we're seeing new side effects that we've never seen before. I don't want to spend too much time on that because, again, I think my colleagues might go into some of this information in more detail. Now, I had to bring those two slides to the forefront because we think that in the setting of having high-risk smoldering myeloma, we could utilize the immune system the same way we do in the relapsed disease. However, we have a more robust immune system. So why not utilize it and try to see how these agents, how these antibodies can be utilized early on? So use of teclistomab and telquetamab in the setting of high-risk smoldering myeloma, seeing how the patients respond after a set number of doses. And again, we use about 24 cycles of the therapy in comparison to other agents that we know about, lenalidomide in this example, and seeing if we, again, can mitigate the progression or reduce the progression to active myeloma, potentially even curing some of our patients. And finally, we have also therapies looking at chimeric antigen receptor T cell therapy. So CARs, we have two of those that are already FDA approved in the relapsed refractory myeloma setting. And in our example here, we are utilizing silt to cell or silt to cap to gene autolysis in high-risk smoldering myeloma. We're trying to treat these patients and see how these patients do. Now, the nice thing about silt to cell, it's a one and done. So you collect the T cells, you do the lympho-depleting therapy, you manufacture those T cells to become the CAR cells or the silt to cells, you re-infuse them, and then you give it back to the patient, and then monitoring of the patient to see how they do over time. So I just gave you a lot of hope and a lot of energy about the excitement that we have in terms of what we're using in treating patients with high-risk smoldering multiple myeloma. I also talked to you about some of the things that we're looking at in the monoclonal gammopathy on-determined significant setting, where we look at MGUS and see if we can somehow learn from MGUS and start maybe treating these precursor conditions, especially in a high-risk Black American population, because why are we waiting until it becomes an active disease before we actually destroy the tumor cells? And so hopefully in the future, we'll have some more information about this. And with that, thank you for listening, and I'll hand off to my colleagues. Thank you, Dr. Harley-Brand. Awesome presentation. I love your presentations. Just very quickly, we did have a couple of questions to come through. I just wanted to, because I get a lot of questions about this from people in the groups as well. When we talk about vitamin D deficiency, the participant says, how does vitamin D deficiency affect African American individuals as it pertains to multiple myeloma? Can you give us a little bit more information? Sure. Thanks, Valerie. I actually skipped over that a little bit. It was on my slide, but I didn't really jump into it because in the interest of time. When you look at vitamin D deficiency in Blacks versus whites, it doesn't seem to have the same negative connotation in terms of myeloma outcomes. I'm not sure why that is because we do see the vitamin D deficiency in both populations, but I'm thinking more it may have to do with what's going on genetically. The vitamin D deficiency in and of itself does not necessarily identify or highlight a poorer progression of disease or a faster progression from the premalignant condition to active condition specifically. But we do tend to see vitamin D deficiency in many of our patients with multiple myeloma. It is worth treating that and managing that, especially in the setting of the damage to the bones and some of the treatments that they may require for bone building. Awesome. Thank you. This is a very quick follow-up there. What are some of the symptoms of vitamin D deficiency that you may be seeing? That's a good question. Vitamin D deficiency, you really have to be essentially somewhat low to have a lot of noticeable side effects. I think similar to having deficiency in calcium, you may have some decreased fatigue and some neurological issues, but it's not the most obvious signs and symptoms, I guess I would say. It's not as noticeable as things like anemia where you're completely exhausted or things like that. Most often our patients do have vitamin D deficiency because many of us work indoors and we just don't spend enough time in the sun as we should. We don't see a lot of striking symptoms, I guess is what I would say. Thank you. Thank you for that. In the essence of time, we are going to move on to the next speaker. We're going to try to get these questions answered though in the chat. I want to take a moment and just turn the floor over to Dr. Patoki, who's going to be presenting on newly diagnosed myeloma patients there. Dr. Patoki? Hi, everyone. Good afternoon and thank you for joining. My name is Dr. Ayo Patoki and I'm a hematology oncology fellow at the University of Miami. I want to say thank you to Health Tree and the Black Myeloma Health Team for the invitation to speak. I'm still in my training, but as you all will see over the course of this presentation, I'm pretty obsessed with multiple myeloma, but in a positive way. I plan to take care of myeloma patients for many years to come. I'm also just really excited to be sharing the speaking platform with Dr. Hartley Brown and Dr. Blue, who are two physicians I really look up to tremendously. I want to say thank you to them for joining and we'll get this started. My task for today was to focus on hope for the future in multiple myeloma, really with the focus on newly diagnosed patients. What I decided to do was to talk to everyone about precision medicine and what it actually means for us for multiple myeloma, especially for newly diagnosed patients. Let's get into it. Since we're here for Black History Month, I really wanted to get us started by thinking about the question, what does it mean to be Black? Some might describe Black race as people of African descent or belonging to racial or ethnic groups that are historically associated with sub-Saharan Africa, but it's important for us to recognize that these racial classifications like Black or African American are really social constructs that can vary across different societies and different contexts. For example, a Black person in the United States might be considered different than a Black person in the Caribbean or Latin America or even Africa. In many places, being Black or identifying as Black is really just associated with this shared cultural experience and shared history that many of us have. Oftentimes, that's shaped by factors like colonization, slavery, migration, and even systemic racism. Those are oftentimes what you'll hear described as the factors that make someone identify as Black, but ultimately being Black or identifying as Black really involves a diverse range of identities, cultures, and experiences. Honestly, what it means to be Black varies depending on who you're talking to. So I wanted to get us started with the idea that we may all identify as Black, but we're also a very diverse group of people. I think it's also important for us to acknowledge the historical context for which we live in. From the 16th to the 19th century, the transatlantic slave trade resulted in the forced migration of over 12 million Africans to the Americas. As you can see on the map, African slaves are taken throughout the Americas, including the U.S., the Caribbean, and South America, as well as Europe and parts of Asia. This massive movement of people led to the mixing of diverse African ethnic groups along with indigenous populations and European settlers. This resulted in the creation of this genetically diverse population with varying degrees of African ancestry throughout the world. This shared genetic ancestor, this shared African ancestry, is just one of the legacies of slavery that continues to impact society and continues to impact our health today. Because of this mixing of ethnic groups, we have a pretty complex genetic profile and we have complex genetic ancestries. This applies not only to the United States, but as I mentioned, the Caribbean and Latin America. Honestly, it applies to almost everyone in society, not just the Black population. What we're finding is that even those who think that they know what their genetic background or their ancestry is, they can sometimes be surprised. It's because of commercial genetic tests like 23andMe and the Ancestry DNA service that we're able to learn more. This map is just one example of slavery's impact. This was a study of European Americans or self-reported white people from throughout the U.S. The researchers looked at these people's genetics and determined the percentage of African ancestry in folks who self-reported or self-identified as white. What you'll find on the map is that the state's now shaded a darker color have a higher percentage of African ancestry among their white population. In the lighter states, their white population is more genetically European. As you can see, the percentage of African ancestry really varies throughout the country. Again, this is just another example of the legacy of slavery and its impact on our genetics. It begs the question, one might wonder, you might say, what impact does my genetic background actually have on my health? Is it playing a role in my multiple myeloma at all? The answer is it depends on who you ask. What we do know, as Dr. Hartley-Brown mentioned, is that Black folks are diagnosed with myeloma at two to three times the rate of other racial groups. For some reason, we're diagnosed at younger ages as well. There are many theories and ongoing research into this area, but in my opinion, we do not definitively know what causes myeloma. We don't definitively know why these disparities exist in the Black community. There are some theories and some studies suggesting that certain demographic groups, certain conditions, and certain exposures may be associated with the higher risk of developing myeloma for everyone, not just us in the Black community. Some of these risk factors might be older age, male gender, or even having a family history of myeloma. There are also some theories that things like workplace exposures or prior radiation can play a role in developing myeloma, and even some suggestion that obesity is associated with higher rates of myeloma, as well as some investigational work looking into the impact of the gut microbiome on myeloma disease biology. What you'll often hear me say when patients ask me what causes myeloma, I say, honestly, it's unclear. But there does seem to be some sort of genetic or inherited factor that's at play in terms of the Black community developing myeloma and having these persistent disparities. There are studies looking at Black and white patients from similar socioeconomic backgrounds. And in these studies, socioeconomic status was really based on education level and household income. And the goal of the project was to control for socioeconomic status and see, does this eliminate the disparities that we see with Black patients with myeloma and their precursor conditions? Or do the disparities where we're diagnosed at two to three times the rate of other groups, do those persist even when we control for socioeconomic status? And unfortunately, even when controlling for SES, we still have a two times higher rate of developing a myeloma precursor condition in the Black community as opposed to other groups, even when we come from similar backgrounds. Along with that, there have been some studies looking at MGUS in the West African country of Ghana to determine if the disparities that we see in the Black population here in the US also applies to West Africa. Because as we discussed earlier, there is at least some shared African ancestry among most people who identify as Black race in the US. And so this study in Ghana found that there is still a two times higher risk of developing myeloma and its precursor conditions among Black men in Ghana compared to white men in the US. So this kind of tells us that the disparities that we see in the Black community here in the US or in our Black American population, they may persist throughout the diaspora. And then lastly, as Dr. Hartley Brown mentioned, there is some growing evidence that there may be inheritable or genetic factors that influence the disparities we see. And so again, before I get into it, I do want to give the caveat that this data is limited, but there are multiple studies showing that people with family members who have myeloma are more likely to develop myeloma or precursor condition themselves. And so again, the data is limited. As far as we know, myeloma does not quote unquote run in families, but there are reports of clusters of families with a pretty significant family history of myeloma as well as other plasma cell disorders. And a few of these clusters of families include Black families. And so this suggests that there may be some sort of genetic or inheritable component to the disease. But again, this data is limited and it's still unclear and will require ongoing work. Now, interestingly, as was already discussed today, when we look at how long people live with multiple myeloma, regardless of how many are diagnosed, it seems that Black patients tend to do well when we're given access to standard or novel therapies. For example, there are some studies that show that after five years, around 54% of Black patients are still alive compared to 51% of White patients. And this data only becomes stronger as we move into the current day and the era of novel therapies. And interestingly, when we receive the same treatment as White patients, there may even be some evidence suggesting that we have better survival rates than other people who are diagnosed with myeloma. One example is a study that looked at Black and White patients who were newly diagnosed with myeloma and ultimately received bone marrow transplants as part of their treatment. The Black patients lived about 7.7 years after their diagnosis compared to only 6.1 years in the White patients. And so these possibly improved or possibly superior outcomes that we see are persistent throughout our myeloma trials where everyone has access to a novel or a standard treatment. When we're given access to adequate treatment, we tend to do pretty well. And so this is something I wanted to be very clear about with my portion of the presentation and for us all to remember that as much as we talk about the disparities in myeloma diagnosis for the Black community, as well as the fact that there are so few of us that are involved in clinical trials, I do want to give the caveat that there is some pretty strong data to suggest that if you as a Black patient are treated with standard or novel therapies, you'll probably do just as well or even better than any other patient with myeloma. So next, let's talk about some of these novel or standard therapies because, as you likely know, the treatment paradigm has entirely shifted from myeloma in a very positive way. And we have a number of highly effective treatments that are available now compared to 20 or 30 years ago when bone marrow transplant was the primary treatment modality. We now have targeted therapies like the proteasome inhibitor Velcade or the amino modulator Reblimid. We've also made significant advancements in the field of immunotherapy with monoclonal antibodies like dirotumab and even CAR-T therapy that's improving survival for our myeloma community. And then I can't ignore the fact that we've gotten better and better at providing bone marrow transplants over the years, making them significantly safer today compared to previously. And so all in all, these treatment options are more numerous today and are more effective today than they were in the past. And this is one of the reasons I personally got excited about pursuing a future of myeloma. And it seems like we're making a difference today and also changing the landscape for our future generations. And so with all these treatments available and them becoming approved for earlier and earlier lines of therapy, it begs the question, what's the ideal treatment for me, especially as a newly diagnosed patient? And as I've said multiple times throughout this presentation, the answer is unclear. But this is where the hope for the future of myeloma and the promise of precision medicine intertwine. And so for those who are unfamiliar, precision medicine is defined as tailored treatment for individuals based on your personal characteristics, including your genetic makeup. And the goal of precision medicine is to provide precise, effective treatments at an individual level. So think of it as the opposite of the one size fits all approach. Unfortunately, we still have a lot of work to do to fulfill this promise of precision or individualized medicine, because generally speaking, we still kind of have this one size fits all approach in myeloma, with one caveat being the distinction between standard and high risk disease. Now, I'll be honest and transparent with you all. As a trainee, understanding high risk disease is something that I've struggled with. And it's not because I'm not understanding or not putting the time in to understand the difference between standard and high risk. But it's because when you talk to different myeloma specialists, you sometimes get different interpretations of what's actually considered high risk. The graphic on this slide highlights the range of opinions in determining what's actually high risk in the myeloma community. For example, at the very top of the chart and at the top right are the international staging system and the revised international staging system, which we generally use to classify standard versus high risk disease. And so ISS and RISS incorporate lab tests and fish studies to determine who is at highest risk for progression. But it doesn't incorporate whole genome sequencing or complex genetics, which we have data to suggest that that is having an impact in myeloma. And there are also some findings that seem to be associated with poor prognosis based on retrospective studies of myeloma patients. So for example, patients with a TP53 mutation or high percentage of circulating plasma cells or even having what we would call primary refractory disease where you don't immediately respond to your upfront treatment. Any of these factors could influence the way your myeloma specialist treats you based on that specialist's interpretation of standard versus high risk disease. And so, as myeloma specialists and in the myeloma community, we're doing our best to estimate who might need more aggressive treatment. But the tools that we have are flawed in the sense that we've been focusing so much on genetics during my presentation today. And there's data to suggest that there's certain genetic abnormalities that are associated with worse outcomes or higher risk disease, but we're still determining. And so as part of this graphic involved in this idea of standard versus high risk disease, at the top left, at the bottom right of the graphic, you'll see the terms chromatripsis and gene expression profiling, which can sometimes be used to identify patients with genetic or chromosomal abnormalities. And the benefit of incorporating genetics is that it can enhance how well we predict how patients will do by accounting for these individual changes in your disease biology, thinking about how patients with similar disease biology to you responded to certain treatments in the past. And so the ultimate goal is that we can improve risk ratification and hopefully guide this personalized or precision medicine management strategy. And though this seems great on the surface, and I'm really excited about genetics, when we talk about genetic-based risk models, it's important to understand that these models need to go through validation. They need tons and tons of data going through them before we can confidently say that the prediction tool that we're using is accurate. And so that means they're going to be tested extensively, and we need to make sure they're reliable and applicable to different groups. And what I really mean by that is that if there's not enough Black people represented in these genetic data sets, we may develop inaccurate estimates of how your disease will progress, which could lead to you being treated with the treatment that may not be the best for you. And so what we're hoping to do is have the best data that we can to help guide our decision-making. And so the big takeaway I wanted you to get from this is that the current models that we use to determine standard risk versus high risk disease are somewhat flawed, and we'll need to incorporate complex genetics studies to really consider how patients are going to respond to treatment. But again, the challenge being that these genetic studies need to be validated on large numbers of patients to make sure that the associations we're capturing are truly a result of the genetics and not just a random observation. And so now I'm going to talk about some exciting work that's going on with the Myeloma Group at the University of Miami, where I work, to build a better risk stratification tool and better prediction model for newly diagnosed patients. And so this is work that's been going on for several years. And these types of projects are still what I would consider in the early days, but I want everyone to bear with me for a moment while I try to convince you that this is the future for newly diagnosed myeloma patients, and tools like this could potentially fulfill the promise of precision medicine and myeloma. So imagine a helpful tool like a personalized guide that's designed to support newly diagnosed myeloma patients and their healthcare team in making treatment decisions. The tool will combine several factors like your demographics, such as age, race, and gender, as well as your genetic data that's specific to your disease, and see how you respond to different treatments, and give a prediction of your survival outcome. And so the idea is that the tool incorporates all this information, as well as patients from the past, to find out. The first question, who is at highest risk for disease progression and might benefit from more aggressive upfront treatment? And secondly, which treatment is most likely to be effective for you as an individual from the very beginning? And so by analyzing your unique profile, again, with your demographic data, your genetic data, and comparing it to outcomes and survival of patients from a similar background as yourself, this tool could help predict your prognosis and tailor some of our treatment recommendations accordingly, and kind of give these personalized insights that we're looking for based on clinical trial data as it comes out. And so that's really the vision. And ultimately, the goal of the project is to empower patients and their health care providers with the information that you need to make informed decisions and really optimize outcomes for every individual with a diagnosis of myeloma. So this preliminary tool and the information regarding its creation was published last month in the Journal of Clinical Oncology, but it's still being validated with more and more newly diagnosed patients to ensure accuracy. And the idea is that the prediction model will get better over time as more patient data is collected, and as we have more time for the treatment and survival data to mature. So when we see how patients respond to certain treatments, that will help us be better informed to figure out how to tailor treatments for patients who come later on. You know, I sometimes think about this as like a chat GPT for newly diagnosed myeloma patients and their health care teams. And so going back to the title of our portion of the presentation, what does precision mean for us in myeloma? And to me, precision myeloma care means tailored and individualized care that's specific to me and my disease biology. So that does not mean that all myeloma patients should automatically receive the same treatment, and it doesn't mean that even all Black myeloma patients should receive the same treatment. Precision truly means studying what works for each individual and refining these practices over time with better data. And precision matters because it can potentially help us improve or even eliminate some of the disparities that we see in outcomes and survival. Because by recognizing and accounting for the diverse genetic factors that we have in our community and among the myeloma community in general, it will influence how we look at disease progression and treatment response, and the idea of precision medicine and individualized care will help us improve care for everyone. And so as excited as I am about incorporating genetics and using prediction tools and big data to improve care for everyone, it's important for us to keep us all in context because these are still kind of the early days of using big data and genetics to predict myeloma outcomes, and it's my opinion that these tools will need time and more data in order to be better validated. But what I'm hoping to convey is that myeloma prediction models incorporating genetics are coming, and we as Black people must be involved if we want the tools to be accurate for us. And so now I'll close out with a summary and a call to action. Today we discussed the shared genetic ancestry within the Black diaspora as well as the fact that there's significant diversity. We reviewed data that suggests that genetics may play a role in disparities in Black myeloma health, and we closed out talking about the hope for precision medicine to bring us tailored, personalized, and effective treatments at an individualized level. And so what I'd ask for everyone to take away from this presentation if you're motivated to make an impact is, you know, number one, get involved in clinical trials. Representation matters, and we need to be involved. And then right along with that, you know, if you're willing, you know, please be open to share your genetic data to ensure that we are represented in these genetic studies, which seems to be the direction that the field is going. And so, you know, as Dr. Hartley-Brown mentioned in the Promise study, if you are interested, if you qualify for the study and you're interested in sharing your genetic data, please do because we need to be represented. And the last piece is, you know, I would ask that you advocate for your friends and families with multiple myeloma to see a myeloma specialist whenever possible. You know, if I or anyone in my family were diagnosed with myeloma, I'd be seeking out an experienced myeloma specialist like Dr. Hartley-Brown or Dr. Bluth, and that's really what I would recommend for all of you. And so with that, I'll close, and thank you for your time. Awesome, Dr. Patoki, thank you. I always love hearing more about the African dysphoria as you present there. Where can we find more information on that IMGUS study that's being done in Ghana that you mentioned earlier in your presentation? Yeah, so that's not an ongoing study. That was actually a study from about 15 years ago, when they looked at a subset of patients within Ghana. But, you know, I am personally interested and hopeful that in the future we'll have more studies, in particular in West Africa, to see if some of these findings that we see in Black patients here are also present there. But that was just one example of a previous study that kind of gave us an idea that there may be a genetic component. Awesome. Very happy to hear about the predictive model too that you mentioned there. I remember reading about that a couple months ago. So very happy and excited to hear more as that kind of unfolds there. We do have some questions, comments here. So we have an individual that has been on that clinical trial with BlinRep. We know that that was pulled from the market. It's recently been bought back. But they make the statement, I've been on the clinical trial, BlinRep, due to high risk smoldering, multiple myeloma, and pair protein numbers are finally at 0%. But they never hear about studies with African Americans regarding this drug. Are you able to comment on that at all? I mean, I know obviously there's the need for African Americans in all clinical trials. But can you comment on that particular one with BlinRep? Yes. Unfortunately, I don't know the specifics of the representation and diversity within the BlinRep trials. And so Dr. Hartley Brown and Dr. Blue have any insight. Please chime in. But that would be exactly as you said. I think it just emphasizes the importance that we need representation in all clinical trials and in all aspects of myeloma care. Yeah, the main thing with that medication is that it was typically brought out to be in what they call the relapsed refractory setting. It was one of the first medications that was approved for that BCMA target that Dr. Hartley Brown talked about. But just due to some issues, it was pulled from the market. And so right now, the plan is to try to bring it back, but earlier lines of therapy. And so you'll see a lot of clinical trials trying to use and incorporate that medication in different ways, whether it be smoldering, whether it be first line, whether it be second line. But it'll be coupled with other medicines that are currently approved. And so there are several that typically are trying to get the medication approved. So it's not necessarily just for the Black population, but it is for the earlier lines of therapy than it was originally approved to be for. So that's typically what you'll see when it comes to research to learn about these things. Yeah, I would echo that and say this is actually a medication which I think, you know, they never they never took it off of the approval in Europe. But we did here because it had a conditional approval when it when it was released in 2020, I believe. So the issue is more to see how this interacts with other medications, how well it pairs with other medications. And it seems to do very well in that setting. And we do have strong data to support that. So to Valerie's point, we may see it coming back in the treatment paradigm for patients. Where exactly it's going to fit, I think, essentially, it's going to be in combination to Dr. Blue's point. But it is a very good medication. It works very well. And I have patients on it who have done amazing. And it's off the shelf, so you don't have to worry about certain effects. And many of the patients who get the vision changes, there are ways to mitigate that and prevent that from being significant. And all the patients who I've had have experienced vision blurriness, it's reversible. So this is not a severe side effect that won't go away. It goes away quickly. You just hold the medication for a few weeks and has a long halfway. So it works very well. Thank you, doctors. So this is a question that comes up quite often. How is the myeloma the age difference that diagnosis? What is the average age of a newly diagnosed white myeloma patient versus the average age for an African-American patient? I don't know this date off the top of my head. It would be either my other co-panelists know. But I believe it's about 10 years earlier they were diagnosed. I think typically the average age of diagnosis for someone of European ancestry is about 69. Typically for African-American, it's about 65. But actually the youngest group that gets diagnosed is actually the Hispanic population that gets diagnosed somewhere between 63 to 64 years old. But again, as we talked about the whole diaspora, once Hispanic and the whole thing gets very Afro-Latina, it gets very gray there. But yeah, so it's typically younger, the youngest group that is affected is the Hispanics than the African-Americans. But then, like I said, typically the average age for the European ancestor is about 69. Thank you. Thank you. All right. In essence of time, we're going to move on to Dr. Blue, who's going to give his presentation on relapse refractory multiple myeloma and talk a little bit about CAR T there. And then the other questions we're going to continue to get to those that's in the chat box as well. So Dr. Blue, the floor is yours. All right. So for the interest of time, I'm going to try to get through some of this quick so we can actually make sure that people actually have time for their question and answer. So bear with me if this makes you think like I'm going a little fast, but I do want to just kind of make sure that people understand what we talk about when we talk about relapse refractory multiple myeloma. So as we kind of already talked about, there's like the early pre-cancer stage, there's the MGUS, the smoldering, and then like Dr. Fetocchi was saying, finally you get diagnosed with this disease and then we start treatment. But what happens is that just like a roller coaster, you'll see there will be ups and downs. And unfortunately, we haven't quite found the cure yet that'll kind of take this disease down and keep it down. And so one of the things that we want to talk about is some of the things that are available in the relapse refractory setting. And so honestly, there's a lot of things that are available, but one of the things that I'm just going to focus on, because that's probably the thing that everybody's talking about, are these what they call CAR-T and bi-specific T cell therapies. And so that's a little bit what I'm focused on. And even though that's what I'm focusing on, just know that that's not the only thing. But like I said, it's a little bit of just kind of a snippet of the options that are available. And like Dr. Fetocchi mentioned, really what's important is personalized medicine. So really the big thing to know is that after people have seen kind of the usual medicines that people typically get from multiple myeloma, just know that the options and the response rate for other medications is pretty low. Meaning that like we have great medicines at the very beginning, but then as each of those little ups and downs happen on that roller coaster, unfortunately, the medicines work a little bit less and a little bit less and a little bit less. And sometimes that means that the relapses are a little bit shorter, a little bit shorter. And so we really needed something that could still work very well in this group of people who've seen so many different medicines. And so that's when people have come through and said, all right, well, let's use the immune system to be able to fight off cancer. And that's really where CAR-T kind of came from. And so the first CAR-T that was approved for multiple myeloma was IdaCell, or people may use the word Abecma. And so right now, the FDA says that if you have at least four lines of treatment, meaning that like you have been up and down and up and down that roller coaster that I just mentioned four times, then that means that you would now qualify for this new medication. The one thing that I mentioned that's super important is that when this drug first came out, there was nothing else available that can give people about 73% of respondents. Meaning that it works in almost three out of every four people that get it. And so I think that's a fantastic use of this medication for people who really didn't have any options that were better than that. There were about one out of every four people that got it completely wiped away, meaning that they were in what we call MRD negativity, meaning that the one in a million like Dr. Harley Brown mentioned, it was basically not detectable. And so what we do is, and he kind of went through some of this, so I don't want to belabor the point, but using that B cell to be able to use your body's own immune system to be able to fight off cancer. And we really saw some great responses. Also, there's another option as well, and they all use this kind of same target that B cell macular antigen or what we call BCMA. So you'll notice that that's kind of the short abbreviation that we all use, but this one was approved in 2022. And so people use the word filter cell, but you almost also may hear the word carbidity. Again, also using the body's immune system, also being able to fight off cancer cells. And again, these are people who, again, the FDA is saying that once you've been up and down, up and down four times, then you would get exposure to this medication. But again, you can see that based off of the research that was done, that over 95% of people who got this medication responded to it. And again, these are people who've seen a lot of different medicines. And so we just didn't really have anything else that worked that well in that many people who had seen that many different medications. And again, half of the people who actually received this medication actually got to that what we call MRD negativity. Again, that means that there was no detectable cancer cells, which is exactly what we want. That typically leads to longer, what we call progression-free survival, a longer time that the disease is under control. And that's really, really, really what we want. So unfortunate thing about it is that there are some disparities when it comes to even new therapy. One of the things that they noticed that with these new therapies, that there's two big side effects. One of those things is called cytokine release syndrome. The other thing is called neurotoxicity. And that for unknown reasons, we don't really exactly know why, but we do see that African-Americans, or I hate to use the word African-Americans, because it's really non-Hispanic blacks is really what we turned to because there were people who were not necessarily from America. But really what we found out was that people who are non-Hispanic black and actually Hispanics had higher rates of these inflammatory markers. And again, like I said, because it uses the body's immune system, the whole question is, what's happening there? What is inherent about people or minorities immune system that could potentially make them a little bit more susceptible to these things? One of the things that's been postulated is that we know that stress creates a lot of issues with our immune system. Stress is like a fire that burns, right? And unfortunately, the body interprets that burn of stress as inflammation. And so if you have the body's immune system, they use it, these cells, unfortunately, that means that sometimes that fire is still burning and unfortunately can lead to sometimes some work toxicities. And so just know that again, some of these data is somewhat preliminary, but we do see that there's even a difference in sometimes how long people have to stay in the hospital based off of some of these backgrounds. And so we don't really know that there's really a difference when it comes to like actually how long they work and those kinds of things. But we do know that they're highly effective for all people. We do see some mild changes in the overall response rate, but we do know that for what's available, meaning that people who what we call triple class refractory have seen really all the kind of mainstay medications that we really were able to kind of use some of this real world data to say, all right, well, let's look at the people who need it the most because we do know that not only do minorities get diagnosed at a younger age, but as I mentioned before, is that we were dying at a younger age as well. And so that also means that we need some of these newer therapies kind of access to kind of make sure that we can kind of break those gaps. One of the things that people are not very aware of is that different than a lot of other treatments for multiple myeloma, you can't just get CAR-T off the shelf. Like you can't just tell your doctor, all right, I'm ready for CAR-T and then you get it tomorrow. Typically what happens is that you first have to come for the consult. You have to meet with a doctor like myself or Dr. Satoki or Dr. Harley Brown. You have to meet with one of us and say, all right, you will qualify. And then what happens that then we have to collect those T cells, that immune system cells. Then after we collect those T cells, then those cells have to be now trained to learn how to fight off cancer. And that could take somewhere between four to six weeks. Now, after that, we can't just get those cells pressed off the plane after those four to six weeks. We have to give you a couple of days of chemotherapy to kind of weaken your immune system so that your body can accept those cells and that there'll be less issues. So the CAR-T process, you know, kind of from start to finish can take, you know, a period of time. And so it's not one of those things that at least as of yet that we're able to get what we call off the shelf CAR-T. And so, you know, we always recommend that people, if you are considering CAR-T, that you start this process early because as you can see, it can take several months. So again, like I said, the two big products that are available now for CAR-T, one is called a Beckmont or IDC cell, the other one is called CAR-50 or Silt-to-Cell. But again, just to know in a general sense, because you typically can't compare one to one because they weren't compared head to head, but just know that they all work in people much higher rates than any of the other things that are available. Okay. And again, when they were compared to other things, again, like I said, they did have higher rates of what we call response rates and longer durations of time that they worked. Okay. So one of the other things that I wanted to talk about, again, Dr. Harvey Brown kind of mentioned this already, so again, I don't want to belabor the point, but basically how do we bring basically these CAR-T cells or these T cells to the actual PANSA cells? And we were able to do that with these bi-specific T cells and basically, you know, it's kind of like when a husband and wife get married, you know what I mean? They basically get married at the hip, you know, and this is basically that wedding ring that combines the man and the wife and kind of puts them together. And the thing about it is that when that toxic T cell sees that PANSA cell, you know, then it lights out and we've seen some fantastic responses for what we call these bi-specific T cell engages. So the first one that was approved is what they call Toclostomab. You might also hear the word like Valley. Again, in that same population of people where the biloma went up and down and up and down several different times, we were also able to see that when we were able to bring that, you know, kind of hungry T cell to that myeloma cell that we saw a lot of cell death and that's exactly what we wanted from that group of people. We see again that it works in a majority of the people who are able to get that with what they call the overall response rate being about, you know, four, three to four out of every five patients, you know, with exactly what, you know, you look for again. And like I said, with people who have seen that many lines of therapy, there's nothing else that really again provided this level of treatment. Okay. Again, those same kind of issues that we see before that cytokine release, also some of those neurotoxicities, we do see again, you're still using the body's immune system. So we do expect that the immune system is going to be revved up. And so there are things that you will notice that when people do get these medications, there will be things like fever, there'll be things like pills, don't see things like the need for oxygen, low blood pressure, elevated heart rate, right? All these things that basically let us know that the immune system is revved up do happen with all these different medications, whether it be these by specific, whether it be the car T cell, because they're all getting very connected. Again, like I said, neurotoxicity is also super important. Sometimes the neurotoxicity is confusion. Sometimes it's headaches. Sometimes it's takes of the hand, what we call tremors. But just know that we do have medications that typically can help with this. But again, it can happen with both to the cluster map, or the device specific therapies as well as car T. So you say, well, what's the difference then as far as when it comes to, you know, kind of time to treatment, you know, the biggest difference is if you came to see again, one of the doctors like me, Dr. Patoka, Dr. Harley Brown, and say, Hey, I'm in this question about medicine or the spices by physics. And typically, we can get that started relatively quickly. You know, what happens is, is that during this process, there is about a week stay in the hospital, roughly, that basically means that during that process in the hospital, we actually give people a ramp up dose, meaning that we because we're revving up your immune system, we don't start off by going 100 miles an hour, we start off going slow, and then we kind of work our way up, we get to the full speed. Because again, these medicines are revving up your immune system. So we don't try to do too much too quickly. And so about by doing that step up those in the hospital, we monitor for that kind of release or those extra symptoms that I just talked about, we monitor for that neurotoxicity or that type of confusion. Okay. And once those things are are deemed to be safe, then you're able to go home. The big difference is that with these medications, they do require continuous injections and continuous dosing as composed to the CAR-P, which as Dr. Harley Brown mentioned is a one and done. So if you compare them side by side, the biggest difference when we see these biases, and again, there's more by specifics that, again, like I said, I probably won't have as much time to go through because I do want to make sure that we have time for question and answer. But this is the whole topic itself that could be much, much longer. But just know that in a general sense, the bi-specific therapies are off the shelf. The CAR-P are your own cells, meaning that this is what Dr. Patoki mentioned, that personalized medicines, you can't get more personalized than taking something out of your own body and then using it to fight off your own cancer. So that's very personalized. They both, again, use the immune system. One of the things that is different is that kind of weakening of the immune system that we do, that chemo that we give prior to CAR-P, we don't have to do that for the bi-specific therapy. One of the things that is a reason for the one and done theory for the CAR-P cell, why we can only give it one time but still have it work, is that because it's your own cell, it what we call expands in the body and it recruits other T cells to say, hey, you see, I'm fighting off these plasma cells, I need you to come and do the same thing. And so because these T cells are able to basically like a living medicine that's working inside, we're typically able to do a one and done. And that's something that, again, a lot of people do prefer. Other thing is that they both do require probably some type of hospitalization. Sometimes people are doing CAR-P as an outpatient, depending on the center. But typically sometimes there's some type of hospitalization required for both. They both can give you, again, that cytokine release, that neurotoxicity. And again, some of those things can vary because, again, there are different levels of confusion, there are different levels of fever and those kind of things. But the biggest difference, as I mentioned before, is that one is kind of a one and done, but it does require you to be at a CAR-P center. These bi-specific therapies are continuous administration and sometimes you can be given locally and sometimes a little bit closer to home. And again, it's something that can be given a little bit quicker because you don't need that kind of engineering process that can take four to six weeks. Again, there's no data that anybody can really say that there's any head-to-head to say that, hey, this CAR-P is better than this bi-specific. So that's not necessarily true. But just know that in general, says most people, if CAR-P is available, will typically try to offer that because we know that that's something that potentially can give people time off of treatment. It can be something that potentially can be something that people can actually get a break from therapy, which is not that common in multiple myeloma management. Also, the things that are super important is that we know that these medications, whether they be the bi-specifics or the CAR-P, need to be more accessible, meaning that most of the time you need to be at a place like Miami or a place like Harvard or a place like Moffitt, some of these big, big places in order to get some of these therapies. But again, that doesn't make it fair because most of the people with these types of cancers don't live in these places. And so we have to make sure that as these new treatments come out, that they actually get to the people that need them the most. One of the other things that also happens not only in myeloma care, but just in cancer in general, is that cancer changes. The reason why we haven't found a cure for this is that the myeloma somehow finds a way to survive and finds a way to adapt itself. And so what we need to do is we need to know that we are not done. We don't pat ourselves on the back by saying, hey, we found this great therapy that works in most of the people and we've given ourselves our time. We say, no, not until we can get this thing cured. Because as good as the CAR-P works, it doesn't cure people typically. As good as these bi-specifics work, they don't cure people. So we need to find a cure for myeloma and we won't stop until we do. I'll stop there. There are other slides, but I'm just going to stop it there in the interest of time because I guess I know we run a little low on time, but thank you. Awesome, Dr. Blue. We're going to get to some questions here. We got some good questions here. Thank you for your presentation there. Awesome presentation as always. We have a participant that says they are a patient that was diagnosed with myeloma recently. It looks like they're being seen there at Moffitt. They also have a 19-year-old son. At what age would you recommend have them being screened for biomarkers? Well, I want to echo what Dr. Harley Brown mentioned about the PROMIS study. That would be the perfect person to enroll in the PROMIS study. The one thing about the PROMIS study is you have to be 30 years old. I know there is a cutoff for 30 years old, but as soon as your son turns 30, I would recommend them to be a part of the PROMIS study. Also, I think what's even more important is for them to tell their doctor that, hey, my mom has multiple myeloma and to make sure that it's something that they tell their kids or that your son has brothers and sisters. Make sure that it's something that's known within the family and it's not something that's kept a secret because, again, we're trying to figure out this whole genetic link, this whole familial pattern. I would say 19 is a little bit young compared to most people, even though I'm sure everybody I've called has seen young people with multiple myeloma. I see college students all the time. I see people who are young and don't meet the average mold of multiple myeloma, but for sure, we want to make sure that that person does get screened and the PROMIS study would be a good way to do it once they turn old enough. Dr. Blue, you talk about CAR-T and the bi-specific therapies. What are you seeing, let's say, at your center with the Black and African American population? Are they taking advantage of these therapies? If not, why do you think that is? Yeah, I think anything that's new, I think that we have some biases that we as a people typically try not to be at the front of any line, just culturally. That's just something how we operate. I think that as this becomes more and more available, I think honestly, I think if you explain it to people the right way, I think people would burst out in the door to get this treatment. I think unfortunately, a lot of times it's not explained the right way. People saying you're taking my cells out of me. I think it takes an extra time to really explain because as you think about it, and this is a whole other topic, but health literacy is one of the things that is super important when it comes to these new therapies because they're very high in the science, meaning that all the stuff that we talked about, this is stuff that is very high level science. You're trying to explain very complicated science to people who probably hadn't been in the science class in 30, 40, 50 years. You really have to take that extra time to explain really exactly what this is doing because otherwise, I think this doesn't make sense. If something doesn't make sense, anybody would be hesitant to do it. I think also more importantly, we have to convince the doctors to actually refer to them and actually come to see people like me, come to see people like Patoka and Harley Brown because if the doctors never refer them, then sometimes people never even get to see us. I think that's probably a bigger issue. Yeah, I agree with you. I'd like to add to that and say we do recognize, I mean, we all know that medicine has not been kind to people of color. There's definitely systemic issues within the healthcare system, including racism. We can't ignore that, right? But when you have that conversation with the patient, you have to acknowledge their feelings and their thoughts surrounding those types of uncomfortable conversations and acknowledge what they may have experienced. Then knowing that, address the therapies in a way that they can understand and they can understand who is going to be involved, who are the providers involved, how it's going to be administered, et cetera, et cetera. But then also to recognize that, as you said, Dr. Blue, a lot of times we pause at being the first in line, not necessarily because we don't want the therapy, but because we're afraid that we don't quite understand the details. Some of that has to do with language. A lot of the times these are complicated therapies and I have a problem mainly with this language thing. I mean, there's so much of the US population is Hispanic and yet when we talk about informed consent for clinical trials or when we talk about giving patients reference material for some of these newer therapies, it's not translated in Spanish or the Spanish version or the alternative language version. It's like five pages, whereas the actual reference material in English is like 20 pages. It does give people pause. There are some things that can be done relatively easily, I think, and some things that may take time, as you mentioned, has to be handled professionally and with care and repeated conversations. But something as simple as translation should be something that we should all be doing. I mean, it's 2024 and I think these are some of the things that we're far cry where we ought to be with some of these things in the health care system. Thank you, Dr. Harley-Brown. And I'll say, now that we have this knowledge about these therapies, go back to your doctors and talk to them. If they're not bringing up those conversations, you start that conversation. Say, hey, I heard about this. Is this something that maybe I may be eligible for? Start to have those conversations with your doctors there. That's okay. That's part of advocating for yourself. Right. Let's look here. So we're going to have a question about, why treatment areas do not use T-cells from a match-alanogenic stem cell transplant donor when offering CAR T treatments to a patient? Yeah. So there's actually been a lot of clinical trials that try to use what we call allogeneic CAR or T-cells. They just haven't quite proven to be work as well. I'll just keep it simple. They haven't seemed to just work as well as your own cells. There's something about your own body immune system that recognizes it and just does such a good job. But there are clinical trials that are still trying to tweak it to the point that that's the goal. You'll probably hear more and more about what we call allogeneic CAR or allocars, more or just more products that can be relevant because again, there's some people, unfortunately, who pass away during that kind of four to six week of waiting on a CAR T and God knows we don't want that to happen. So for sure, timing is everything. And so there'll be more to come on there. Dr. Poole, I want to go back. I remember when you were here with us last year and you talked about CAR T being used in the upfront setting, closer to being used in the upfront setting. Can you give us an update on that? And is that something that we can still kind of hope, have some hope in? Yeah. So there's a couple things. So we're hoping everyone in the myeloma community is hoping that, as I talked about that up and down four times, that the government will approve CAR T to be approved in earlier lines of treatment. We're hoping sometime 2024. We're hoping that that'll be the case. But from an upfront setting, there's going to be some clinical trials that try to what we call dethrone the king and the king right now in myeloma care transplant. And so there's going to be some trials that come out and they try to compare CAR T versus transplant and try to see if what's going to happen there. Now transplant has been around for longer than I've been alive almost. And so it's going to be hard to take down, but it is something that I think is exciting because CAR T is a much less toxic thing. We prefer not to give transplant if we didn't have to, but it works. And so because it works, we still offer it. And so if there is something that can work better but be less toxic, I think that would be a win-win for both the patient and the provider. Yeah. Awesome. Awesome. Awesome. And just to piggyback on that, it looks like there was a question about a stem cell transplant. Can your collection be used for CAR T therapy and how would that work? No. So typically there's different products that are what we call aphorese or collected during that process. So no, but one of the things that people are starting to do that if you were to need what we call a boost, sometimes people's immune system just needs a little bit of a boost. So sometimes you can use stem cells to kind of give a little bit of a boost if people do run into like an infection issue. But to use it for CAR T, no, that would be, it's a different process. Okay. Awesome. Thank you. All right. We've got just time for a couple more questions here. I see this question about tremors. What do you guys recommend that could help with the tremors? Anything for this individual maybe dealing with that? Yeah. So sometimes the tremors can be a result of what we call the neurotoxicity, but sometimes it can actually be a sign that people can actually be developing something called Parkinson's. So typically what we do is we typically have people who have those tremors see a specialist called a neurologist who is a nerve and kind of brain specialist, and they can help us delineate the type of tremor it is because different tremors mean different things. And so if people are having tremors, they still have a specialist called a neurologist as part of their kind of care team, and they'll be able to help kind of delineate kind of what the best next step would be. Okay. Awesome. And then lastly, are there over-the-counter drugs that you could recommend as far as like herbs, teas, vitamins that could be used in fighting off disease progression? Anything you guys can think of? I know it's, Dr. Harley Brown, I see you. Go ahead and take that one. I always tell my patients that you want to eat healthy, you want to have a healthy diet as much as possible. I think as long as you can try to maintain your health, the healthier part of you in its optimal state, that's really what matters. I don't specifically have some particular plant or soup or tea that I would definitively recommend, but we mentioned some of the risk factors of obesity. So if you find yourself tending to be in the borderline or maybe obese, then look at some of the things that you're doing, some of your habits, and maybe try to improve upon those, and that would include some of the dietary habits as well. We do have some studies that are looking at myeloma and these precursor conditions, M. gastrointestinal smoldering, and the microbiome and then the gut and seeing, you know, is there something that we're exposed to in our foods and what we eat that may be somewhat predisposing us sometimes, or the immune system of our gut, like how that interplays with some of the things that we are exposed to. But those are early studies, and you know, a lot of them we don't have enough information on to really make a definitive decision about specific things in your diet. So healthy is always a little bit better than unhealthy, as much as you can. Awesome. Thank you. Thank you all for being here. I do want to take a moment just to give you opportunity for closing remarks. Dr. Fertoki, I'll start with you to have any closing remarks this afternoon. No, I just want to say thank you to, you know, everyone for joining us. Thank you for the panelists. I thank you to the panelists for joining us and just another encouragement to advocate for yourselves, seek out a myeloma specialist, get involved in clinical trials. Awesome. Awesome. And Dr. Blue? Yeah, I just want to say thanks for the invitation. I just want to hopefully that people remember all the things that we say today, and if people want more information, you can always bottle up on social media. I'm Dr. Blue MD on all social platforms, and hopefully this won't be the last time that you guys see us all together. Dr. Harley Brown. It was a pleasure working with all of you today, and I love the questions from the audience. I think you have some very intelligent questions, and I just hope you can take away from this that we are improving the outcomes for patients in myeloma. Let's remind ourselves that this is a disease that affects the Black community more than other populations, and, you know, there's empowerment in community and, you know, groups like this, so let's use that as a stepping stone towards getting more involved in clinical trials and more involved in, you know, empowering ourselves and getting treatments that are newer and seeing specialists. We have enough specialists out there that you should be able to at least have them be a part of your team, even if they're not your primary local provider, you can plug into them through different avenues, so get involved and get the care you need. Thanks for inviting me. Thank you. Thank you all for joining us, and thanks for all of your support in the Black Myeloma Health community. If you haven't had an opportunity, definitely go over and check out our website, blackmyelomahealth.org. And just a reminder, we will be meeting next month, March 28. Dr. Sakinda Alawadi from the Mayo Clinic in Jacksonville will be joining us. Just a few other outdoor announcements. On Tuesday, February 27, the Plasma Cell Leukemia Chapter will be meeting, and they will be discussing understanding the recent plasma cell leukemia clinical trials. On Thursday, February 29, at 5 o'clock, the Amelio-Dois community will be meeting. They'll be discussing the role of stem cell transplant in amelio-doises. On Monday, March 4, at 5 p.m., the MGUS and smoldering chapter will be talking about a nationwide trial for smoldering myeloma patients. The link to sign up for any of those events and even more that I haven't mentioned today can be found at the bottom of the slide, and also will be sent to you in a follow-up email within 48 hours of this event's completion. As always, I take a moment to say thank you to our sponsors, without whom this would not have been possible, J&J, Kite, Genentech, BMS, GSK, Sanofi, and Regina Braun. And thank you for helping us build a strong Black Myeloma Health community. I appreciate each of you and hope that you enjoy the rest of your day. See you next time.