(Guest Lecture): MGUS and Smoldering Multiple Myeloma (SMM) | MCRT Webcast: MGUS and Smoldering Myeloma (SMM)

[Music] so again jenny thank you for the opportunity to be here um this morning or afternoon as you said um it's again um really nice to see that a lot of you have joined um the called uh to hear about the monoclonal gammopathies which clearly is an area of great interest um for both the physicians taking care of patients with myeloma and related disorders and obviously for a lot of people who are living with those um conditions and what i'm going to try and do this morning is show a few slides so use the slides as a way to just introduce the topic and talk about it a little bit and as you already heard from jenny we're going to have a q a section which is probably going to be taking the bulk of the time today after dr gabriel's presentation as well so i'll just start off by talking about the you know the main actor when we talk about the monoclonal bodies and those are the plasma cells and these are mature white cells of the basal family and they all have a very important function which is making antibodies or immunoglobulins to help us all fight infections while abnormalities of the plasma cells can lead to a variety of different disorders what we are going to focus on today is the malignant transformation or the abnormality in the plasma cell that leads them to proliferate or divide in an uncontrolled fashion leading to the spectrum of monoclonal gammopathies and what they do is normally to secrete immunoglobulins as i said these are proteins that your body uses to try and fight infections now they are made of two what we call heavy chains which are bigger molecules and two smaller compartments or two smaller pieces which are the light chains now the heavy chains can be five different types and i'm sure many of you have heard about this already in your reports they are typically they are either igg or iga so and in a smaller number of patients it can be igm and rarely ige or igt and the light chains which are the smaller pieces they are the kappa or the lambda type typically they all are bound to each other so there's two of those heavy chains and two of the light chains that are bound together and secrete us what we call an intact immunoglobulin so when we talk about this whole family of abnormalities called the monochromatic themopathies they are all symbolized by the presence of clonal plasma cells so these are plasma cells but they are abnormal and that's why we call them clonal because they all originate from what we believe may be a one or two abnormal plasma cells which they continue to grow in an uncontrolled fashion and they all typically would secrete these immunoglobulins or at least the light chains the gap or the lambda light chain which is what we refer to as the monoclonal protein and this monoclonal protein can be present either in the blood or they can be found in the urine so when you think about the monoclonal gammopathies as a spectrum and this is just an example of the number of patients that we have seen at mayo clinic over a long period of time you can see that the vast majority of the people who have a monoclonal protein in their blood or urine have monoclonal gamma but they have undetermined significance and this number here is probably underrepresented because of the the fact that you know more patients with conditions that need to be treated like myeloma are more likely to be referred to um at your hospital like mayo clinic so if you were to just go out and look in the in the community and identify people with the monoclonal protein um suggesting a monoclonic homopathy 90 plus percent of those patients will have what we call a monoclonal gammopathy of undetermined uh significance or mgos [Music] as jenny already mentioned for some reason this light seems to have its own life um so the less common are the smoldering multiple myeloma and then obviously patients with multiple myeloma and amyloidosis and a variety of other related conditions um that typically often needs some treatment so the mangas and the smoldering myeloma are two conditions that we often refer to as precursor diseases to multiple myeloma because as jenny already mentioned all patients with myeloma have to have had monoclonal undetermined significance at some point in time now where do we typically find plasma cells right to make that diagnosis of monoclonal gamma pretty as i mentioned we depend on often the presence of the monoclonal protein and in some of the patients also the presence of monoclonal plasma cells and as you can see here on the left hand side these are how the plasma cells look like in a bone marrow they all have this darker nucleus that's typically pushed to one side and then they have that bluish what we call the cytoplasm or the rest of the cell that takes up the rest of the cell in this picture so typically we would find that in the bone marrow when you do a bone marrow aspiration or a bone marrow biopsy but you can also find that in what we call plasmocytomas which are basically the swelling so soft tissue or bone related deposits from body can do biopsies where you can see sheets of these plasma cells and if you do more sensitive testing we can also find them circulating in the bloodstream as you can see on the right hand side again those cells with the nucleus pushed to one side now what about the the monoclonal protein or the immunoglobulins of the light chains now for the years what we have the way we have identified them is by using a test called protein electrophoresis which can be done either on the serum or from the on the blood or they can be done on a 24-hour collection of the urine and again you can see on the um on the left-hand side um the of these electrophoresis is a normal looking one and on the right hand side you can see what we what is marked here as a m spike and this is what [Music] represents the abnormal protein which is secreted by these abnormal cells now the electrophoresis tells us how much of the m protein is there or the m spike is there but it doesn't tell you what type of m spike you have and for that we use a test called diminifixation where we can again break them down to see are they a g heavy chain or a heavy chain in this particular example it's a g you can see this dark band up here and lower down you can see a dark band in demonstrating or suggesting that this is a kappa light chain so obviously this particular example the person has a igg kappa monotone protein and in about 15 percent of people we may not be able to show that they have a heavy chain but they may still have a light chain that is in excess and those patients we can detect or rather measure um the serum light chains by using it that's called the free light chain assay and that will tell you whether there is too much of a kappa light chain or too much of lambda like chain and also tells you how much of light chain is there now the reason why we want to measure these monoclonal protein is because that is one way we would track how the monoclonal gammopathy is doing over time so um one of the questions that always comes up is what causes monoclonal gammapathies now we don't completely understand why someone would develop these abnormalities in the plasma cells and the plasma cell starts dividing without any control but we do know that there are certain subgroups of patients who might be at a higher risk of getting them one of them is the african-americans we know that they have a higher risk due to threefold higher risk compared to caucasians we don't have very good data from the asian population or the hispanic population but it's widely believed that they may be at a lower risk than caucasian we know that people who have been exposed to chemicals or radiation exposure have a higher risk of getting monoclonal commodities similarly we also know that first degree relatives of people with the monoclonal gammopathy have a two to three for higher risk of have getting monochromatic amount or being diagnosed with one so when you think about this whole spectrum on the this the initial stages is the monoclonal thermopythy of undetermined significance of mothers which everybody has before they go on to developing small ring myeloma or active myeloma and in some of the individuals we can identify a phase that we refer to as small during myeloma before it actually becomes an active or symptomatic myeloma and what happens during this transition from mgos to active myeloma the first thing is the increasing amounts of monoclonal protein that you can measure on the electrophases and if you were to do bone marrow biopsy we can also see that there is increasing amount of plasma cells in the bone marrow and what really makes the myeloma stand out is because now you're having issues um related to the m protein or related to the monotone plasma cells that you start having problems with your kidneys or your bone and which makes it very clear that we need to do something about it but in between the smaller myeloma phase you don't have any of that side effects or the what we call the end organ damage but increasingly we are starting to look at this group of patients to see can we actually do something to prevent it from going to active myeloma can we do something before the other shoot drops as jenny was mentioning so how do we know who is going to get myeloma right that is the import that is what always is uh the difficult thing to predict um and for people who are living with the monoclonal thermoplant determine significance or smoldering myeloma they are under this constant concern that myeloma is going to um going to come on what we know is that patients with monoclonal of undetermined significance as you can see in the lower line the risk of getting myeloma is about one percent per year and remains constant over time um so even though the risk is low the risk is always there which means we have to continuously um monitor these patients in contrast those with smoldering myeloma have a much higher risk so almost half of these patients would get myeloma in the first five years either 16 15 percent over the next five years and after that it's about one percent per year so the key thing is if you can very specifically identify who is going to get myeloma then not only can we do something about maybe trying to prevent it from happening but we also can reassure the remaining people that we that they don't have to keep worrying about this getting to myeloma so there are a lot of different ways we have tried to identify those people who have what we call a high risk smoldering myeloma or high risk muggers just to identify those people with a higher risk so that we can watch them very closely now the good thing uh is that you know if you watch patients with smoldering myeloma very closely uh their risk of getting something dramatic very drastic um or you know the kidneys just shutting down um things like those things don't happen overnight and we have we do have plenty of warning as long as we can watch these numbers very closely but it's obviously we don't want to do that for everyone we want to do that for the people who are at the highest risk and we also don't want to try and do some treatment for everyone we want to try and intervene only when they have the highest risk of progression so there are different models that have been developed one of them has been this recent one the 20 to 20 or 20 20 20 which looks at the bone marrow plasma cells which look at the free light chain levels and also um look at the um the m spike levels to see who are at the highest risk now this is only part of the story and actually as dr gabriel will get into there are several other factors that can also be used like the the genetic makeup of the plasma cells which can tell you uh who might be at a higher risk of progressing to um active myeloma so that maybe we can do something about it so um again so i think the important point i just wanted to make get across to everyone is that you know the majority of the patients in or people in whom we've identified a monoclonal protein we don't really need to do anything about that other than just watching them very closely and i think as we try to understand the the mechanisms through which this progress i think we will be able to tell those people who are at the lowest risk to or reassure them and so that we don't they don't have to constantly worry about it and the people who are at the highest risk maybe we can really do something about it to try and alter that risk of progressing to active myeloma so maybe i'll stop there and i think there are a lot of questions maybe this we use that as uh opportunity for question answer sessions um and all later on thank you [Music]