(Guest Lecture) Interpreting MGUS/Smoldering Myeloma Labs - What to Know and When to Take Action

we're going to be talking about interpreting MGUS and smoldering multiple myeloma labs, what to know and when to take action. MGUS and smoldering myeloma patients and their care partners need to know what numbers to pay attention to and when to worry. So many doctors tell MGUS and smoldering myeloma patients to watch and wait. Well, what are you supposed to be watching for? And how do you know when the waiting period is over? We want to make sure that you are empowered with the tools and the education that you need in order to properly take care or take initiative in this part of your care. So what are those levels that indicate active multiple myeloma? When should you talk to your doctor about concerns? Today we get to hear from these two myeloma medical professionals as they teach you the answers to these questions so that you can become a more educated and empowered patient in your precursor myeloma journey. Marilu is one of our speakers today and she is an international medical graduate who joined Health Tree in 2022 as a part of the patient experience team. She helps MGUS and smoldering patients understand and track their lab and genetic test results and relevant information from their health history. She is a Disney fan and travel enthusiast, a passionate novel reader, a cheerful, friendly person, and she really is. You guys are going to love her. And a good listener who enjoys spending time with family and friends. Arturo is an international medical graduate who joined Health Tree in 2020 as part of the patient experience team. He helps patients understand their disease panorama and navigate their myeloma through the tools and resources that Health Tree provides. He is an enthusiastic photographer, tech nerd, and aspiring food explorer who loves to travel and find exciting experiences. He is also a genius, but he was too humble to put that in his bio. So with that being said, I will turn the time over to these two for their excellent presentation that they have prepared. Thank you guys for being here. Thank you, Audrey. Thank you, Audrey. Hi, everyone. Today we're going to discuss how to understand your lab results, especially in the context of MGUS and smoldering myeloma. Knowing how to interpret your labs is one of the many tools that will help you become an empowered patient and will facilitate communication and share decision making with your health care team. The topics that we will cover today are these. First, I will talk about the importance of understanding your labs and what it is useful for. Then Marie-Lou will cover how to actually understand them and interpret them. In this section, she will cover myeloma basics to understand the biology behind the labs that we need to look at. Then she will talk about the MGUS and smoldering myeloma labs that are directly related to the plant muscle activity and correspond with the behavior of the disease. Then she will talk about the other important labs that are not directly related to myeloma or plant muscles, but are essential to identify progression to active multiple myeloma and evaluating if other organs are being affected. Then she will go through the MGUS and smoldering myeloma criteria, which is important to keep in mind because it will help us to know if you have progressed and when we have to intervene. Finally, we will wrap up the session with a Q&A. By monitoring your labs, you can identify progression. And you can take action in a timely manner. Taking action in the context of MGUS and smoldering myeloma can look like identifying future treatment options if the disease progresses because when you are diagnosed with MGUS and smoldering myeloma, you are in a place where you have time to consider all the treatment options without the pressure of having to take a decision at that moment. So it can be beneficial to consider your plan of action if the disease were to progress. You can also stay up to date with lifestyle changes that could potentially prevent progression. There are multiple studies and trials investigating the role of diet, exercise, supplements, alternative medicine, and other tools that might help us prevent or slow the progression of disease. Implementing this into your lifestyle could also potentially improve your quality of life. Then we could also actively monitor your labs so you can know if a change in your current monitoring plan is needed. There are different actions that we can take with patients with MGUS. For example, you can discuss with your physician what are your monitoring options. Maybe when you need to do your checkups, maybe yearly, every six months, every three months, or which are the most relevant labs for you to check at that moment. You can also identify clinical trials for which you might be eligible. As you know, at the moment, the standard of care for MGUS is the watch and wait approach. This might be frustrating for some, and since we don't know why some patients progress while others don't, it's difficult for a doctor to know when to start intervening. This is why there are clinical trials that aim to find out more about this. The observation of clinical trials try to find the characteristics of the MGUS patients that progress to multiple myeloma or small myeloma, and the interventional trial tests potential drugs that can help us stop the progression. There are not many clinical trials for MGUS, which is why it's important to identify if you meet the criteria for any of the available trials, and understanding your labs will help you with this. Taking action with small myeloma can be different depending on the risk of the small myeloma. For example, for high-risk patients, the best course of action could be an early intervention, because we already have FDA-approved drugs for these cases. But for all the other cases, we can have clinical trials that are specific for small myeloma and monitoring options to track if the small myeloma can progress to multiple myeloma. We can also identify clinical trials, observational and interventional, that can help us know more about the disease and when it can evolve to multiple myeloma and how to stop this evolution. Knowing your labs will help you identify if you can meet the criteria for these trials. This is the natural progression of the disease from MGUS to small myeloma to multiple myeloma. Not all patients go through all these entities because it depends on when we catch the disease, but it's important to keep in mind this when we evaluate your labs. Monitoring your labs is essential so that you can identify whether your disease is stable or if there is a risk of progression to any of these entities. Finally, by understanding your labs, you can also understand if you are a standard or high risk of progression, identify whether the disease is stable or if it's potentially progressing. And then you can also identify opportunities for joining clinical trials for which you meet the criteria as we mentioned earlier. These are some of the reasons why it's essential to monitor and interpret your labs. Now Mari Lu will show you how to understand your labs. Thank you Arturo. So hello everyone. Thanks for being here. We will now talk about multiple myeloma and precursor condition. So multiple myeloma is a type of cancer of plasma cells. This means excessive amount of plasma cells due to an uncontrolled production. If we're going to talk about cancer cells, I think we need to all go back a little to a biology class and you see in the pictures we have cells dividing, I think you'll remember. So in a simple way, cells are intended to grow, reproduce and die after completing their task or cycle. And if they get out of line or start malfunctioning, cells should be able to start off line or start malfunctioning. Cells should get repaired and get to work back again. So when a cell stops working as they should, as you can see a distressed cell over there, they should somehow by any chance avoid this repair process. They should stop dividing and follow apoptosis, which is programmed cell death. But what happens when cells do not get repaired and do not follow apoptosis? Well, these cells manage to start dividing and reproducing in an uncontrolled way, which later on will develop into a tumor. In this case, an uncontrolled production of plasma cells will develop into multiple myeloma. So now let's talk about what does a normal plasma cell should do? Well, healthy plasma cells produce multiple proteins called immunoglobulins or IG for short. IGs are proteins that attach to foreign substances entering the body and will help us fight infections. So a normal, it's having a variety of immunoglobulins that help us this way. But what happens when we have an abnormal plasma cell instead, which has reproducted uncontrollably? Multiple myeloma plasma cells. These myeloma cells produce a specific abnormal protein called monoclonal protein, also called M-protein, also called M-protein, M-spike, and a few other names to make it more complicated. So as we said before, cancer starts from one cell reproducing nonstop and making copies of the same cell over and over again, just as a copy paste. This is why myeloma cells secrete only one type of abnormal immunoglobulin that cannot properly fight infections, making too much of one type reduces the ability to create a wide spectrum of immunoglobulins to properly fight infections. And as these myeloma cells grow, other blood cells inside the bone marrow starts to crowding out. So this is what an excessive plasma cell prediction looks like. And as you can see, how easily can crowd out some other cells. So I think now we understand a little bit more about all of this. What should you focus on while monitoring your labs? Well, first of all, it is essential to know your subtype, and we will explain this in a few as well. Then you should pay attention to the following labs. We have the myeloma labs and CREB. So for myeloma labs, we have the M-spike or M-protein, the free light chains, either kappa or lambda, the immunoglobulins, we said Ig, that we have IgG, IgA, IgM, IgE, and IgD, and of course plasma cell percentage. And for CREB, we want to take look to calcium, creatinine, EGFR, and hemoglobin levels. Okay, so the first thing we said is really important and essential for all of you is to know your MGUS or smoldering myeloma subtype. This will help you know what to look for while looking to tons of your labs. So if you take a look at this image, this is what an Ig or immunoglobulin look like. As you can see, it's formed by two parts. The first one, the bigger and green part is the heavy chain, a shape one of white. And we have, as we said, IgG, IgA, M, D, and E. And then we have a smaller, we call it lighter, blue part that's called light chain. And this is what an IgG look like. All plasma cells secrete only one type of immunoglobulin. Each one of them has different purposes. And the normal thing is to have a variety to help us find bacterias, allergies, or infections. And as all myeloma cells come from one original cell, all the myeloma copies will secrete the same subtype the original did. So for example, we can have an MGUS patient with an IgG kappa subtype. Or maybe we can have a multiple myeloma patient with an IgA lambda subtype. Small during myeloma patient with a kappa light chain only subtype. So there are many different combinations and many different subtype. So this is why knowing your specific subtype will help you keep track of the myeloma plasma cells and not other remain healthy plasma cells. So as we said, the protein that is secreted by the myeloma cell is the M spike. Or also called monoclonal protein, monoclonal immunoglobulin, M spike, M protein, and some others. And keep in mind that the reference value for the M spike is always zero, which means that anything above this value is considered out of range. We can find this M spike in the protein electrophoresis test from sewer or urine samples. Keep in mind M spike has many names, so knowing this can help you find them easily. This test measures the free light chains that we've said we have kappa and lambda. And it is important to know your subtype and keep track of your light chain values as well. As we said, we have several types of Ig's or immunoglobulins. In this case, we need to pay attention to your specific heavy chain and see if it stays inside parameters. So if you are a small during myeloma patient with an IgG kappa subtype, you need to take special attention to the IgG levels. And also please remember that if one heavy chain starts to increase, crowds out the other Ig's and the other values you might see them decrease as well. Then we have the ratio. And this is just the balance between the kappa and the lambda light change. If a patient has a kidney damage, the normal ratio may vary. Plasma cell percentage. These is obtained from a bond myrobiopsy. And depending on the plasma cell percentage found can tell us among other things if the disease is progressing. So as seen here on the picture, the healthy patients should have less than 5% of plasma cells and no crab. We will go back to crab later on. Then for MGUS patients, we can find plasma cells between 5 and 10% and also no crab. For small during myeloma patients, we can have plasma cells between 10 and 60%. And again, no crab. For multiple myeloma or active multiple myeloma, we can have two different situations. If they reach 60% of plasma cells or more, and still no crab, oh, or if the crab is starting to show, even though plasma cells are in 10% or more. So remember the amount of plasma cells can vary depending on the region where they take the bond myrobiopsy. Some doctors have referenced this with a chocolate chip cookie being poked with a toothpick. So imagine the whole cookie is the bond myro and the chocolate chip is the plasma cells. So we don't know the amount of chocolate we will get on the toothpick and this may vary if we try again in some other places. Okay, we talk a lot about crab, but what is it? So crab is the acronym that will help you remember signs of active myeloma. So C stands for calcium, high calcium. R stands for renal insufficiency. A stands for anemia, can be represented or found in low hemoglobin levels. B stands for bone lesions on imaging reports. It is also important to keep track of crab the same way of myeloma labs, because these will warn us of early signs of multiple myeloma. Okay, so for the C and R, calcium and renal insufficiency, we can take a look at the comprehensive metabolic panel. So to keep the calcium in levels, we refer them as 8.4 and 10.2 milligrams per deciliter. In high calcium may result in constipation, loss of appetite, weakness, drowsiness and confusion. This is why to keep them in those levels. Elevated serum creatinine or low EGFR could mean kidney damage. So this is why we would want to keep creatinine between 0.5 and 1 milligrams per deciliter and EGFR above 60 milliliters per minute. Anemia can be traced in a CBC, also known as complete blood count. Here you will want to focus on hemoglobin results. Multiple myeloma cells crowd the bone marrow and it can cause some blood deficiencies. Low hemoglobin is a sign of anemia and it could also represent progression to active multiple myeloma. Some symptoms can be fatigue, weakness, pale skin, dizziness. So here you will want to keep an eye on hemoglobin levels and this should be between 12.1 and 15.9 grams per deciliter. Okay, so I know I've been talking a lot about numbers, but actually the key to follow your lab results is trends. So pay attention to trends instead of just a single lab result number. Keep an eye on the big picture. A single lab result cannot represent your overall status. You do need a baseline. So this will be the starting point and comparison from the following labs. This baseline can be the day of your diagnosis, in maybe some cases the progression from MGOS to smoldering or from smoldering to active myeloma. Or maybe the baseline could be the start of a clinical trial. Trends can help you understand how your condition has been changing over time. So if you do notice an abnormal trend on your labs going up or going down, ask your doctor about it. Now the last part of CRAB, the V from bone lesions. So imaging tests are really useful and are able to reflect osteolithic lesions that cannot be seen without an x-ray. These lesions are also a sign of active myeloma. As Artur said, we have two precursor conditions of myeloma, MGOS and smoldering, which is closer to myeloma. Not all patients get diagnosed with a precursor condition, but the criteria for each is this. So for MGOS patients, we have less than three grams per deciliter in their serum M-spike. And if this serum M-spike starts rising between more than three grams in serum M-spike or five grams per deciliter in urinary M-spike, it can indicate progression to smoldering myeloma. MGOS patients have less than 10 percent of plasma cells in their bone marrow. And if this percentage reaches 10 or increases even more between 10 and 60 percent, it can also show progress to smoldering myeloma. Both MGOS and smoldering are asymptomatic and no CRAB. This is some of the changes that we would like to keep in mind in showing signs of active multiple myeloma. Now, for the smoldering myeloma patients, we have a risk stratification criteria from low to high risk. This criteria is mainly used to determine if a patient may be or not eligible for a specific clinical trial to reduce their chances for early progression to myeloma. But please remember that patients with high risk also have good outcomes. There are other many things that can influence patient results and not only a risk stratification. We will take a look at the serum M-spike, plasma cells, free light chain ratio, and chromosomal abnormalities. For each criteria the patient meets, we will add one point and depending on the final score, we will add the risk. If the serum M-spike stands greater than two grams per deciliter, it will add one point. If plasma cells are above 20 percent, it would also add one point. If the ratio is greater than 20 percent, it will also add one point. There is the additional risk factor. Having any of this chromosomal abnormalities, we also add one point. We have the translocation 414, translocation 1416, gain 1q, deletion 13q, and monosomy 13. If a patient scores zero at the end, it will have low risk. If it scores one, low intermediate risk. If it scores two, intermediate risk. If it scores risk. If it scores two, intermediate risk. If it scores between three and four, then high risk. This is the multiple myeloma criteria. Knowing this can help us know when our labs are reaching to active myeloma once. Myeloma is diagnosed, as we said, with 10 percent of plasma cells and the presence of crab, or when plasma cells reaches 60 percent without crab, or when the free light chain ratio increases and reaches over 100. Okay, so as a quick summary, first of all, it is essential to know your specific subtype. Keep your labs up to date and monitor your labs, especially the myeloma markers and the crab. Keep learning. We have multiple resources here at Helltree University that can help you better understand your precursor condition. But also, if you don't know where to start, there are many things we can help you. If you ever feel lost with all your labs, do not hesitate to schedule a call with us. We can help you understand your precursor condition. We can send you a personalized email understanding your labs with the explanation of your latest myeloma labs. We can share resources. So, is there a specific subject you would want to know more about? We can send you links to Helltree University depending on your concerns. If you want to join a clinical trial, we can help you see if you are eligible. There are many clinical trials for high-risk smoldering myeloma patients, and there are even some trials for MGUS patients. If you ever feel worried about your condition, we can help you find a myeloma specialist near you and so much more. So, please remember we are here to help you. And now I think you're ready to understand a little bit more about your labs. We thank you all for assisting. We love seeing you all here. And please, please, please, if you ever need assistance, do not hesitate in contacting our team. You can send us an email at support at helltree.org. You can call or text anytime to our 800 number. So, it's 800-709-1113. And thank you again, everyone. Thank you, Marilu and Arturo. You guys did amazing, and I love how interactive your slides were. And looks like people are already asking questions. Arturo's been busy answering some of them, and let's keep asking them and getting these answers. So, one of the questions here, and Marilu, I'm going to direct this to you. You said MGUS is asymptomatic, yet some, many people I know, have MGUS who also have peripheral neuropathy. So, is it truly asymptomatic? Wow, that's an excellent question. So, I will want also Arturo to help me on this one. Arturo, any insights? Sure. So, the classification of MGUS has been with us for many years, but over the years we have found many different classes of what would be a monoclonal neuropathy. There are some patients that are not actually MGUS, but maybe they have kidney damage, or maybe they have, as you mentioned, peripheral neuropathy. And in this case, it's important to assess the patient's case because although they may not be multiple maloma or smaller maloma, they may need treatment for this problem. So, the classes of MGUS are changing, and we have a monoclonal neomalty of clinical significance or of renal significance, and probably more are going to come over the years when we know more. Yeah, I'll just echo and say, like Arturo was saying, the MGUS diagnosis is constantly changing as they're investigating more and understanding more about precursor maloma. Like Arturo said, there's now MGCS, monoclonal gammopathy of clinical significance, or of renal significance, so MGRS. And these are very new classifications. And in fact, when I ask people to, as specialists, to come speak on these things, they're just not prepared enough because there's not enough information out there. But that being said, they are aware of more and more MGUS patients presenting with renal significance, presenting with this neuropathy that you're referring to. So, the answer is, is MGUS truly asymptomatic? Yes. Is it also maybe related to other symptoms? Yes. And then it's really hard at the MGUS stage as well. And I see this question later, so I'm going to ask the follow-up with this question. It's hard in the MGUS stage to know, well, is it coming from your MGUS, or could you be having neuropathy from other things that are going on in your body? Other comorbidities, other pinched nerves, things that maybe we're not considering and we don't necessarily want to blame it on the MGUS if it's coming from something else, which is why specialists are so cautious in this MGUS stage to say, oh, the peripheral neuropathy is for sure coming from MGUS. So, the question that was related to what I just said is, how can you tell if low hemoglobin or anemia is a Crab issue or if it's unconnected to myeloma? And if the hemoglobin is lower than normal, what action is required? Not sure which of you would like to, Marie-Lou, go ahead. I will start and then Arturo can jump in any time. So, let's remember also that because sometimes it's uncertain to know, this is why we need to keep also our doctor with one hand. So, they are the ones that should know when extra task is needed from their hands. So, maybe extra studies or maybe get deeper research in why is this happening when it started. So, do not forget also to always reach that hand next to you. Yeah, I would just add, and Arturo, you're welcome to add as well, that's why it's so important not only to have a doctor at that one hand, but to make sure that doctor is a specialist. It doesn't matter that you have MGUS, it doesn't matter that you have precursor myeloma, if you have smoldering, even intermediate risk smoldering, low risk smoldering, whatever it may be, having a myeloma specialist at your side is extremely important because they are staying on top of this kind of crazy myeloma research that's being done right now. We're learning so much more about precursor myeloma than we've ever known before. So, having a myeloma specialist on your side is extremely important. They can help you. They're more aware of what tests should be run to figure out is this myeloma related or not. So, just wanted to add that. Arturo, any other comments? Sure. So, also it's important to always ask your doctor if maybe you need to change the frequency of your checkups because your myeloma labs, the myeloma proteins that are loose plane, always go in hand with the symptoms that they are affecting. So, if your hemoglobin is going down and your myeloma labs are going up, then they might be related. But you may need to have checkups more often to make sure of that. So, that's why you have to always ask your doctor to make the changes of your monitoring as needed. Wonderful. Thank you. One of the questions here is how can smoldering myeloma have a zero score? It's impossible. Would that be considered MGUS? Marilu, do you want to take... Oh, Arturo. Arturo, go ahead. Okay. So, with smoldering myeloma, it's a really difficult topic because there's more that we have to understand. We know that high-risk smoldering myeloma has high risk of progressing to multiple myeloma. But for all the different stages of smoldering myeloma, the only definition that changes everything sometimes is the percentage of plasma cells. The percentage of plasma cells tells us that something is happening there, but sometimes our body is good enough to handle everything. Sometimes our body can handle the smaller myeloma or a really low level smoldering myeloma all the rest of our lives, but sometimes it can't. So, that's why it's really important to keep up with your labs to make sure that you always remain at a zero score and that you don't change over time. Great. Thank you. We have some really great questions here and I'm really excited to ask them. Okay. So, Helen's wondering, if your labs are high but stable for years with no crab, how often should you get a bone marrow biopsy to check for your percentage of myeloma cells? So, it depends. If they are smaller myeloma, usually they repeat it every six months, every year. And sometimes if they don't see changes over the years, they don't see any changes. Maybe they do it less often, yearly or every three years. It depends on the patient. But for M. gus patients, it might be even five years or some even don't come back until they have signs of something that they want to check up. So, it depends really on the case. The guidelines for small myeloma are one to three years for the checkups and the guidelines for small myeloma is from six months to one year. Yeah. So, from M. gus, it's one to three years. It's okay. Yeah. And like Arturo was saying, it's definitely a conversation to have with your doctor. It depends on how often you've been tested up until this point, how frequently I mean, and then how frequently you guys can have an educated discussion about if you've been stable, what that's going to look like in the future. And so, kind of, yeah, that was another question here. It's related but a little bit different. If your M protein test results are negative, do you still need a bone marrow biopsy? And if so, how often? So, the problem with the plasma cells is that sometimes they don't behave as with all the patients. Some patients may not present any M-spike during the course of the disease, even when they evolve to myeloma, because their M-spikes are not producing, their plasma cells or myeloma cells are not producing the M-spike at any moment. Sometimes they only produce light chains and some other times they only clone themselves but don't produce anything. So, that's why a bone marrow biopsy is always needed to confirm my diagnosis, just to make sure that we don't have one of these rare cases that are not producing any protein. Thank you. All right. So, we talked about MGUS being asymptomatic. Why is smoldering myeloma defined as asymptomatic as well? And let me just say, just like MGUS is constantly changing, smoldering is that times 100. People are wondering what to do about smoldering myeloma diagnosis. There are some specialists that are even advocating for the smoldering myeloma diagnosis to be taken away so that it's just MGUS and active myeloma. So, this is a complicated question. There's definitely high, especially as you get closer and closer to that high-risk smoldering myeloma, you're going to see people start to present usually, sometimes not, sometimes yes, I love myeloma. It's so simple and easy to understand. But yeah, so I'm not sure if you guys want to tackle that question, but just to preemptively say it's complicated. Yeah. Yeah. Sometimes the symptoms as the earlier question about MGUS maybe sharing neuropathy is a difficult question because the doctor has to see the complete panorama of the disease. In some of our care cases, there are symptoms, but they are not as common and they may not be identified as easily. So, in those cases, specialists may be needed to make the diagnosis of multiple myeloma or something else. So, in summary, smoldering myeloma by definition is asymptomatic, but sometimes the ones that were diagnosed with smoldering myeloma may have symptoms because it may not be actually smoldering myeloma, but there is still so much information that we don't know. And that's why researchers need people to get into clinical trials to really get these answers. Thank you. Marie-Lou, if you want to hit this one, and if not, you can pass it along to Arturo. They're asking, can you provide any reference of literature describing how high-risk abnormalities carry a strong importance in the evolution of MGUS to smoldering or multiple myeloma? And can we elaborate on that importance? I definitely will ask Arturo. He's the genie one with all the literature at hand. So, one really important thing is that this literature will change. Sometimes it changes every month. So, one thing that I would do is to follow the article that we are publishing in eHealthy because we are doing that job for you. We're looking for the most important articles that are coming out, and in your case, you can search for the ones on smoldering myeloma. Usually, we have conferences like Ash or ASCO that give us really good answers to important questions on smoldering myeloma and MGUS, but it's difficult to keep up. So, I would say stick to eHealthy and always send us messages because these will vary over time. I would stick first with the Ash articles that we just published, and then we can go to more specific questions. I will also add that Jenny does an amazing job with the newsletter. So, subscribing to the newsletter is also a great way to keep updated on anything related to myeloma. As Arturo said, we did that a lot for Ash. So, you can find several articles in a friendly patient way to understand complicate, like really hard to know ideas and that doctor says so. You can find them better explained at Healthree. Yes, I'm pulling up, somebody's asking about how to identify a myeloma specialist. I am putting as an answer to that, I'm putting our link to the specialist directory that we have on our website. We've organized it by region geographically, so you're able to see most of the myeloma specialists that are in your area. A myeloma specialist is considered somebody who sees around 100 patients per year if they're in a highly populated area. If they're in more of a rural area, it's at least 50 patients per year, and somebody who's actively involved in myeloma research, whether that's writing papers or actively involved in clinical trials. So, that's somebody that you would want on your team as a myeloma specialist, and the people that we have on our page meet that criteria. Okay, lots of other great questions. So, let's keep going. Desiree was saying, I was in an observational study for MGUS. I used to get lab kits to send, but now I haven't received them in a long time since COVID started. I was screened for another MGUS study, but now my MGUS was not severe enough to qualify. My thoughts on the original study, there were no questions about my lifestyle to see if that would affect progression. Desiree, first of all, thank you for participating in a clinical trial, and I'm sorry it wasn't the experience you wanted it to be. Unfortunately, as Arturo was saying, there's so little MGUS trials out there, and they definitely need to be improved upon in the way that they're organized. Easy for me to say as someone who has never organized a clinical trial in my life, but thank you for what you're doing so far, and we also agree with you that we hope that that improves as time goes on. Ruth is asking an interesting question, and if you feel comfortable answering, Arturo, I would love to hear your thoughts. Ruth is wondering, how long will it take for the multiple myeloma vaccine to be available? So, if you could briefly explain what she's asking to audience that may not know about what that multiple myeloma vaccine is, and then your thoughts on the tiny. Sure. So, actually, there are multiple myeloma vaccines being tested in clinical trials. The general way is that they are trying to use immunotherapy to try to teach our immune system to identify myeloma cells or malignant plasma cells, and that way our own immune system can tackle this problem. They're being tested currently mainly for multiple myeloma to know if they can stop the progression or slow it down. There are not many studies researching general population or small myeloma or MGUS, because they first have to know that they work, and the easier way to know is with a patient that already has multiple myeloma. So, all these vaccines have to go through a process. They first have to be tested on multiple myeloma patients. We have to know if they make any change for the myeloma patient, and then after they get approved, they will be tested in different aspects, and myeloma patients, MGUS patients, and maybe the general population. So, it's a process that probably will take time. It may vary depending on the results, but yeah, it's coming soon. Yeah, and initially the first trials did not go as well as they wanted. So, trials did not go as well as they wanted it to. So, they're currently adjusting things and trying to get things working conceptually. It's a great idea. People are really excited about it conceptually. It's just figuring it out in a clinical trial and then advancing it forward. Okay, Marilu, if you want to answer, what is the light chain ratio of? What are the two numbers that we're comparing? Great. I was just typing, but yeah, I'll say it out loud. I'm sorry. No, no, no, it's great. So, when we talk about this, it will be kappa over lambda. So, kappa will be on top, and lambda, it will be the other part. So, you do this division, and I will give you the ratio. So, kappa divided by lambda. Awesome. Thank you. Jim is saying, my labs mentioned total protein and creatine. I don't see anything that mentions M-spike or the other terms that you mentioned. Are there other names for M-spike that would be on a lab report? Well, they make it even harder, but yes. So, normally, you will find it in the electrophoresis test, and you can find it as M-spike, M-protein, monoclonal. As you can see in this slide, there are like 10 different names, but specifically, it will be on the protein electrophoresis test. And this is a good opportunity as well. If you want to briefly call up our team and say, hey, I'm trying to find this number. Can you give me some synonyms that might appear? This is where they can definitely help you, and even like Marilu just did help you locate which test it's even going to be under. It's so complicated. I don't know why they don't make it easier. And it's not the same across different facilities either, which makes it even more difficult. Okay. So, Dorothy's wondering if you could share a little bit more about the following as smoldering myeloma subtype. Doctor says that she has infectious subtype of high IgGa, and if I have active myeloma, it will be more difficult to treat. So, let's talk about the risks involving IgGa, all of the different subtypes. And Arturo, if you want to go with that. Sure. So, the evolution usually with, I will go with the most common type IgGkappa is slower, is the most common type. This is also the one that's known to be less aggressive, but this will vary depending on the type of Ig that is affected. One way to determine which could be more aggressive is by the amount of IgGs that we usually have in our body. For example, for IgG, usually we have a greater amount than all the other IgGs, but for IgA and IgM, usually they should remain in lower numbers. So, when they go really up, they take much more of the space of all the other proteins. They take more space of all the other immunoglobulins because for starters, they should be lower. So, the main way to determine the risk might be to which is the normal number of your IgG. If it's higher, then the risk should be a little bit lower, but if it should be really low and it's really high, then the risk is usually higher that way. Yeah, and it sounds like you already have a doctor who's aware of this, which is good. If that doctor is not on our specialist list, I do recommend that you see one because it can get so confusing, and having someone that understands myeloma in and out is going to be really helpful in your journey. So, a couple people are having questions about inactive multiple myeloma. People really focus on translocations and the risk of those kind of translocations, such as 1Q gain. Is 1Q gain something to be concerned about when you have precursor myeloma? So, 1Q gain is an abnormality in which usually you should have only two chromosomes, one, but then you have one extra part of one chromosome, the Q part. This part is important because in this part, there is a code that tells the cells to reproduce faster. So, when you have an IQ, it doesn't matter if you are M-gloss or smaller or M-gloss or whichever type of condition, it will tell the cell that it should reproduce faster. So, it's the same case for either case, but usually it's more relevant for myeloma because for M-gloss, as they are in really low numbers, it might not be a big difference. Is it a known risk factor that it would progress faster to active myeloma? Yes, but it's really important only on the smaller myeloma. M-gloss really depends on the number of copies of 1Q. If you have only one, it's not really a big factor, but if you have two, three more, it may be important. Great, thank you. Lymia is saying that they have noticed the IgGa and lambda light chain are increasing regularly for more than a year, but it's still within the MGUS protocols. Because it's been increasing consistently, is this something that they should be concerned about? Or when should they be concerned about that threshold to smoldering myeloma? When does that become a worry? It depends on the trend, on the frequency of these changes. If these changes have happened over the years and they are not really important, then maybe the disease will remain stable for five or ten years. But if this trend starts to go faster and faster, going up more and more like in a cure, then you might want to go to a specialist to make sure that you are not progressing to a smaller myeloma or even myeloma. Yeah, definitely. I will want to compliment that. When we said have a myeloma specialist on your team, it doesn't mean that you need to quit every other doctor. Having a myeloma specialist can see you maybe just once a year and just give you a heads up, a direction where to go and what to do. Maybe you just need one, two appointments and he can talk to your oncologist or to ametologist and they can just build a stronger group to help you get this. So when we say talk to a myeloma specialist, don't feel like you need to quit your team or just add the captain to your ship. Very good point, Marilu. Thank you for that clarification. Mary is wondering what lifestyle changes should a person make to slow progression? Mary, that's an excellent question and something that people are studying. I'll let you guys answer this in just a second, but Dr. Irvi Shaw, she's at Memorial Sloan Kettering. She's dedicated her life essentially to figuring out the answer to this question. She's specifically studying the impact of diet and nutrition on MGUS and smoldering multiple myeloma patients. Can a whole food plant-based diet curb progression? Can turmeric or curcumin affect this? She's going into the depths of this and trying to figure it out and we should have results within the next, I hate to say it, but five years of her intense and amazing studies that she's getting funded. And then Dr. Jens Hillingas, who's at Roswell Park in Buffalo, New York, he is studying the impact of fitness on myeloma progression. So are you, you know, the more active you are, not necessarily running marathons, but if you're staying active, can that curb myeloma progression? And as you guys know, these are things that take time to study, but it can also benefit you in other ways, as Arturo was saying in the beginning, can improve your quality of life. If you decide to add more vegetables and more fruits to your diet, more whole grains, if you decide to be a little bit more active in your lifestyle routine, this can help lower comorbidities, this can help improve your quality of life and improve your mindset, which has been proven to have less stress, which has been proven to benefit you overall. So there's not necessarily a direct connection between, yet, between change your diet and you'll stop myeloma progression or change your, up your fitness levels and you'll stop your myeloma progression, but there's certainly great correlations that come along with increasing your fitness according to your abilities and improving your diet to include more whole foods. Anything else that you guys want to add, Marilu and Arturo? I think you're a rocket. Yeah, that's exactly. And we were going to talk about Dr. Esparra, which is, she's amazing. And yeah, I think, and we have tons of results, resources and Houchi University where she speaks a little bit more about this. Wonderful. We are reaching the end of our time, but we'll stay on for just a couple more questions because I know a lot of you have these great questions and then our team can even take a look at these questions afterwards and send out answers to people that did not get their answers live. Sorry to volunteer you guys for that, but now you're a volunteer. Okay. So Otis is wondering, there are two ways to measure the percent of plasma cells, bone marrow smears and blood tests. Which one is more accurate? And Arturo, if you want to take that one. Yeah, the best way to, or the most accurate way to follow any plasma cell condition is with the bone marrow, but it may be a difficult procedure because it's too invasive. So it's related to the way that, to the type of disease, for a small amount of one year every six months, the sperm goes maybe one year, two years, two, three years, because of this painful procedure. So it's better to follow the labs, the blood labs, in a more frequent way. And the bone marrow biopsy only with this frequency, although it might be better. Great. Thank you. Okay. So Dorothy is wondering, I've just been recently diagnosed with smoldering myeloma. When is a referral to a multiple myeloma specialist indicated? I would talk to the person who diagnosed you and ask for a recommendation right away. The sooner the better when you have somebody like that as a part of your team, like adding them to your team. And then I see a question here, is CAR T treatment good for smoldering myeloma? It's currently not available for precursor myeloma patients. In fact, it's only available for relapsed and refractory patients through FDA approval. And current clinical trials are trying to move it up for induction therapy for active multiple myeloma patients. And I'm not sure it would ever go to precursor patients just because it's such an intense procedure. And there's so little levels of myeloma in protein, but we'll have to see. Arturo, can you answer Desiree's question of what is the difference between multiple myeloma and Waldenstrom's macroglobulinemia? So the main difference is the type of immunolumine that's affected. If I remember correctly, Waldenstrom is IgM. The way that Waldenstrom behaves is kind of different. In multiple myeloma, you have the fracture, you have the anemia, you have the kidney damage. But in Waldenstrom, it might be less intense depending on the risk, but it might have different symptoms that are related more to the way that the blood flows. So you may have more vascular problems. Thank you. Dorothy is wondering if a transcript will be sent to all patients. This meeting is being recorded and we will send it out to all registrants as well as the slides which we're sharing today. So hopefully that helps. And with that being said, I think we're going to finish up, but I promise for those, let me just finish this one. They were asking if I could write in the chat the names of the doctors. So it's, and you guys forgive me for my spelling. I should probably spell better for the career that I'm in. But anyway, that was Dr. Jan Silling-Gass from Roswell Park who's involved with fitness and Dr. Irvi Shaw from myeloma memorial Sloan Kettering, myeloma Sloan Kettering, who is involved in the diet studies. So thank you guys so much for joining. And again, our team will work on looking through these questions and answering those that did not get answered so that everybody is able to get access. And thank you Arturo and thank you Marilu. You guys did amazing, amazing presentation and great job answering these questions. If you want to stay and answer a couple more questions while I'm closing up, you're welcome to. Otherwise, just thanks for being here. I appreciate you guys. So remember as you leave the session today, we'd love to have you take a survey. It will prompt you to take a survey as soon as you end the session. It just takes about one to two minutes and it tells us what you liked about today, what we can do better next time and what future topics you have for the MGUS smoldering chapter. In March, we're going to be talking about what treatments are available for high-risk smoldering myeloma patients, as well as why it's not available for low-risk, intermediate risk and just tackling that whole treating smoldering myeloma in the room. So make sure that you join us in March. This chapter is going to be every other month in the year of 2023, which I can't believe we're in 2023 already, but here we are. If you'd like to join us tonight, we're also having a labs discussion. If you live anywhere from Maine to Pennsylvania in the Northeast region of the United States, you're welcome to join us for our active myeloma labs discussion. Then on January 17th at 1 p.m. Eastern is our stem cell transplant chapter. We're going to be discussing preparing your home post-stem cell transplant. And then on the 18th is our Mountain West community chapter. So that's Montana, Idaho, Wyoming, Colorado, Utah, Nevada. If you're in that area, you're welcome to join us as we have an acupuncturist coming to tell us how acupuncture can and has been proven to benefit the cancer and myeloma community. The link to sign up for any of those events and even more events I didn't mention is found at the bottom of our slide and will be included in that follow-up email that I've been referencing. As always, we thank our sponsors, Wissamayers Squibb, GSK, Genentech, Abbey and Amgen, without whom this would not be possible. And a big thank you to each of you for helping us build this MGUS smoldering community. It's such a pleasure to be with each of you. I hope you have a great rest of your day. Thank you everyone and take care. Bye-bye.