[Music] what is the progression of myeloma from precursor conditions to act at myeloma when we have certain criteria then we call this active myeloma so the difference between smoldering myeloma and active myeloma is just presenting with end-organ damage meaning you've damaged enough organs that we have to treat you and I would say let's step back and say any other cancer you never do that you never wait for someone to have a fracture or an emu or kidney failure and then you treat them so by the finish in the word active myeloma versus smoldering myeloma is a misnomer everyone has myeloma and it's a question of do they need treatment or not and what are the criteria of treatment we've already moved the bar from crab criteria alone into let's add a few more which was we call slim crab and hopefully in the future we will add a few more to make sure that we treat at the right time what we don't want to do is over treat certain patients who will never progress to myeloma and that's the gray area this is where we don't know who are those patients we should treat and we have an opportunity now to do it in the right way to do it scientifically rather than just putting one marker and treating everyone one of the topics that I asked I was asked to address is this concept of smoldering and M goes what I show there is how we classify things but before I go into the details and I hope this is pretty obvious this is completely arbitrary the reason we put certain cut-offs for values of the protein concentration of the number of plasma cells is you said when we write papers and we talk about the clinical studies we have some common understanding of what we're going to talk about but this boundaries are man-made they're completely artificial and how do they work well at the extreme left you have the M goes or the monoclonal gammopathy and that is their very earliest age we have for detection of expansion of this plasma cells this abnormal plasma cells and we put the boundary at 10% because someone has more than 10 percent plasma cells then they're technically considered smoldering myeloma and then the next boundary to active myeloma is when we have what we call end or and damage or when someone is having complications because of the growth of the cells and then of course you see in the last two stages is when the cells they just they decide they can live outside of the bone marrow they can be in the blood they can have extra medullary presence and that's kind of the more advanced stage of the disease now this is as I mentioned completely arbitrary so if you have a person who has you know 11 percent plasma cells 12 percent plasma cells are they is smoldering or an EM Gus it really doesn't matter it's about the same as if they had nine to eight percent and this is sometimes easier to teach than it is to live by and what I mean by that is when we see patients in the clinic boy who was do we scratch our heads you know someone comes to us with plasma cells of 35 percent and they have a very mild anemia and and we go you know should we pull the trigger should we recommend that they start on treatment or not not a very easy decision to make sometimes the extremes are very obvious you know if someone comes with a high calcium with kidney damage it's very obviously that person needs treatment if someone comes with a tiny protein a perfectly normal hemoglobin it's obviously don't need treatment but there's a lot of them between so this is this is a very very important concept that you know it's not mathematical things it's not that you can do a computations we will tell you exactly what you need to do we always need to look at the big picture as we see patients now I'm not going to spend a lot of time you've seen this this slide already from from dr. Morgan and how we look at those proteins and you see the EM spike again but just know when we when we talk about M goes this is a rather common condition dr. Robert Kyle who is a person who started the myeloma group up in Mayo Clinic Rochester was the one who coined this term the M dose and he has established the parameters by which we understand how this affects the general population and what he has found this you know it's something that keeps going up as we go up in age as you can see up to you know 7.5 percent of people over the age of 60 of 85 will have an M goes so people can have an M ghos and you go to the doctor and you know they do some testing and they find the Monica protein and then they have a symptom and then the next question of course is that symptom related to that monoclonal protein and it may or may not be related and that link or that connection sometimes it's pretty hard in the clinic we see a lot of those patients you know someone who has back pain and now they have this small monoclonal protein is that myeloma or is this just someone who has back pain because they have spinal stenosis and now they have an M goes that's that determination is one of the most important things we do in the clinic because you know our accommodation of whether someone should be treated or not of course dictates a lot of what happens on the line so that's something we have to be we have to be very careful about now what else do we consider when we talk about M goes so first of all we we haven't made enough emphasis about this and I don't know if there's anyone in the audience but as you know we classify the proteins into the IgG IgA and the IgM if you have an IgM 99 percent chance you won't develop myeloma 99.9 percent chance you won't develop myeloma that's associated with another condition called Waldenstrom's and that protein is usually not associated with bone destruction and the usual things for myeloma so that's why it's critical to differentiate that from from the other ones the ones that are not IgM number two there's some patients that have very low protein so you have an EM spike you know less than 1.5 or you know the low free light chain the risk of this progressing to myeloma is very very low it's estimated at you know 5% over 20 years of course we'd like it to be Syrah but it's just something that is very rare it's unlikely to happen and for most of their patients whether it's a ghost or smoldering at the minimum you should be testing for the markers on an ongoing basis because we want to make sure that you know we we intervene if needed before complication starts so for an M dose patients we say at least yearly for smoldering multiple myeloma patients we do that more frequently and if you're in the audience and you're dealing with M Gosar smoldering these are some of the some of the red flags you should be aware of so bone pain now we'll have the possibility of having pain in our joint or bones for other reasons the most common one of course with aging is stiffness right people wake up and say go home you know it's hard and you need to warm up the the one thing that makes myeloma different from that is that myeloma pain is like the pain you would have with a fracture so you know you have a fracture you move and it hurts a lot you put a cast to mobilize it doesn't hurt so that's the pain that we worry about with myeloma so if a person tells me you know I wake up and I'm stiff but I kind of get going I get my coffee I feel better I feel nah that's not myeloma but if someone tells me I wake up and boy I start moving in my back hurts or at night when I present my ribs they they hurt that's worrisome for myeloma associated bone disease so that's one of the things the second one is myeloma is almost never in the joint it's almost always in the shafts and myeloma rarely happens below your elbow so below your knees because we don't have a lot of bone marrow there so so you know again stiff joints not myeloma and you'll become very self aware of course when you have a diagnosis like smoldering painting your ribs and your back or in the shaft of the legs or weight-bearing that's concerning for myeloma of course someone has fatigue or generalized weakness we want to know about that for instance for anemia you know constitutional symptoms those are those are things that would worry us and I put in a list of other things I won't go into the details but when we see patients who have this diagnosis in the clinic we're paying a lot of attention to all of this to see if there's anything that would raise a little red flag for us to look into further now classically you've you've heard about this whole thing with a crop criteria which is what dictates whether we need to start treatment or not and the acronym starts for C for calcium a for anemia R for renal or kidney and B for bone now they rarely happen in isolation usually there's there's a few of them that come together when someone is progressing and I wrote a paper a few years back that I call it the claws of the crab and what I meant by that was as follows there's two the crowds have claws and they have legs right but the dangerous part of the crab is a claw and what is the dangerous of crap for myeloma is both renal and bone disease the reason I say that if you have a high calcium we have a very good chance of controlling that that's usually not a problem we can take care of that if you have a knee Mia we can take care of that what we don't like to see it's long lasting damage because of bone destruction the B or long lasting damage to the kidneys now we do have very good markers for for kidney disease that the free light chain is the number one risk factor for the kidneys being affected if you come to Mayo Clinic and we had a conversation about this at the table if you come to Mayo Clinic we have a free light chain under 100 your risk of kidney damage is pretty low now the reason I say if you come to me a clinic most other institutions use different units they use milligrams per liter so it'll be at a thousand so you have to look what there's milligrams per deciliter liter a hundred and a thousand that's where we have the risk for kidney damage so we pay a lot of attention to that we don't have very good markers for prediction of who's gonna get bone disease but you know those are the two that worry me the most so if I have a patient who has small grain don't worry too much about the calcium don't worry about anemia we can always fix that if the free light chain is low I just want to make sure I asked enough about the bones that I get the imaging studies to have some reassurance that there won't be progression to to a fracture now the criteria has changed recently because we realize that there are some patients who have smoldering who have a significant risk for progression in the in the short-term so the international myeloma working group got together and decided we need to refine this a little bit further and and what was decided is that if patients have extreme smoldering situations and and what we mean by that and I won't go into all the details if someone has more than 60% plasma cells if someone has an extreme abnormality and the free light chain or if they have two or more lesions on their MRI you might as well start treatment now instead of waiting for those those complications to ensue so that's something where we're you know looking at very carefully so this is just in a in a nutshell what you know we're thinking about with regards to smouldering and two and two M girls like situations now a common question we get and I know many of you have received treatment once you're in treatment you're not back into M ghosts are smoldering embers are smouldering is completely reserved for those patients as a diagnostic criteria who have never seen treatment now we may say you're in an M ghost-like situation like if someone has a transplant and has a small protein and that protein stays there forever that's okay it seems like an M goes but the diagnosis is reserved for those who have never received treatment previously