What are precursor conditions of multiple myeloma?

[Music] water precursor conditions of multiple myeloma precursor conditions of multiple myeloma include monoclonal gammopathy of undetermined significance or M Gus and smoldering myeloma monoclonal gammopathy of undetermined significance means that an elevated monoclonal protein can be detected but the individual does not have active myeloma and may never go on to develop myeloma amiga's is found in 3 percent of the population over the age of 70 and this number grows as people get older I'm Gus is also more commonly found in African Americans than Caucasians dr. Robert Kyle of the Mayo Clinic identified this condition in the 1960s and named it M Gus according to dr. Kyle M gus proceeds all active myeloma we do know that each and every one of you has had a monoclonal protein in your blood or in your urine prior to your development of multiple myeloma now this protein has been present for probably an average of 10 to 15 years at least before it is recognized however today don't feel badly because there isn't anything that we can or well that we should certainly or that we can do because you have that protein abnormality dr. kyle shares the story of the first patient he had where he noticed this condition and named the condition M Gus let me say a few words about the first patient I've often times made the comment that patients have taught me everything I know and this particular patient did I was reviewing the history of a patient named mrs. ahlstrom who had been seen at the Mayo Clinic 19 years before because she wasn't feeling well she was worked up and found to have a increase in the globulin in her blood but that was as far as one could go at that particular time and she was told to go home that her blood work was otherwise good she returned 13 years later at which time serum protein electrophoresis was doable and this showed a very large spike in her serum of about 2.9 grams per deciliter and she remained asymptomatic and again was told go home and enjoy life and to to then she seven years later developed symptomatic multiple myeloma with bone pain and all sorts of the problems and had myeloma recognizing this story I kept my eyes open for others and actually others appeared and was able to collect 241 of these individuals and published it and called it I didn't know what call it I called it monoclonal gammopathy and I used the term undetermined significance but probably in retrospect a better name would have been unknown significance because it was determined by this by this protein per se M Gus requires no treatment and there's a 1% chance per year of developing act of myeloma what is smoldering myeloma smoldering myeloma is a stage just before active disease were active - Milo itself is characterized by having end-organ damage meaning bone lesions or fractures or anemia or kidney failure anything before that is a precursor to myeloma and one of the stages is smoldering disease which is between M Gus and active myeloma and just like the name says it's almost going to be milo it's small dream there but it's characterized by having 10% plasma cells or cancer cells in the bone marrow but not having any symptoms you don't have fractures and you don't have kidney disease however there is a high chance that you could develop myeloma so we want to watch you carefully but then she even put you up with treatment to prevent progression in general the chances are 10% per year to develop myeloma or 50% at five years there are some people who have something called high-risk smoldering myeloma which is even higher chance of developing it and this is a 50% chance at two years to develop active disease or end organ damage now how likely is it that a patient was smaller on myeloma will develop active myeloma one study found that the overall risk of progression was 10% per year for the first five years approximately 3% per year for the next five years and 1% per year for the last ten years the cumulative probability of progression was 73% at fifteen years there are three risk levels of smoldering myeloma that depend on a few key factors according to dr. Sahgal oniel of Emory University an average low-risk smoldering patient will not develop act of myeloma within ten years if they have only one of the following features a serum and protein level of more than three grams per deciliter more than 10% plasma cells in the bone marrow or a free light chain ratio greater than eight or less than 0.125 but no significant anemia renal failure hypercalcemia bone lesions or amyloidosis as these would be symptoms of active myeloma patients have intermediate risk smoldering myeloma and will typically progress to active myeloma within three to five years if they have two of these features and patients have high-risk smoldering myeloma if all three features are present and are likely to progress to act of myeloma within a two-year period these patients may want to consider joining a clinical trial and starting treatment in solid cancers in breast cancer or in colon cancer we're doing screening all the time for our patients so when I'm age 40 I go for my mammogram or colonoscopy when we're a little bit older and if you see a small little polyp or if you see something in your mammogram usually we have things removed immediately and we don't say well why don't you wait until you have lesions in your bone or you have metastasis of breast cancer and then I'll treat you yet for blood cancer we see every single day a patient with MCAS and we tell them oh wait until you have myeloma wait until you have leukemia and then I'll treat you and that whole idea of watching weight is something that we've inherited with all been taught this way and it made sense probably in the older days when we had no treatment we had no effective therapy and the treatment was actually very harmful so if you're asymptomatic and you're doing well it makes sense not to treat you but these days with us understanding all the mechanisms of clonal evolution of the tumor cells are not sitting as you know things that are not acquiring new mutations as we leave them alone and as we understand better the immune microenvironment that as the tumor cells grow more and more they're able to make your immune system worse and worse and as we understand all of this it doesn't make sense for us anymore to say well why don't we just watch and wait until you have a full-blown disease until you have metastatic myeloma and then I'll treat you and that whole concept is is something that we need to change in our mind as physicians we need to change for our patients but start to prove it also clinically we cannot say yes it doesn't make sense we have to actually truly prove that early treatment makes a difference in the survival of patients with myeloma and if we prove that then suddenly we're changing everything we're changing the way we think of our asymptomatic patients walking around but you can also think that 3% of the population over the age of 50 has MCAS and that's a huge number of people that were not screening for we're not looking for them and if we know that we can make a difference in their life we should be starting to look for them and screen them and instead of just doing a mammogram or a colonoscopy or even checking your cholesterol level and making sure you don't get a heart attack and you die from it we to make sure you don't have em Gus and you will develop myeloma in 20 years from now and I can prevent myeloma and the whole idea of prevention that myeloma will happen is such an interesting concept right that we can think of preventing heart attacks these days because we're very good at it and just giving an aspirin and controlling your cholesterol it could be as simple as that in the future for us in myeloma but we just need to make the steps we understand about us you understand who will progress and who will not because we don't want to treat everyone we can not treat the whole population to prevent 10,000 cases or 15,000 cases and we need to develop the right trials for the right patient something that's not toxic that's not forever we don't want to treat patients forever to prevent one case we want to truly have more of a surgical intervention just like we do in breast cancer but in this way it's a medical but very concise and very non-toxic therapeutic intervention for those patients dr. irene Gabriel at Dana Farber is running two important studies for precursor conditions the P crowd study is an observational study where M Gus and smoldering myeloma patients can send in blood and bone marrow samples the promis study is the largest screening study in the world for family members of myeloma patients and all African Americans participants donate a blood sample so we can learn why people progress from these early conditions to act in myeloma to find clinical trials that M Gus or smoldering myeloma patients can join go to health treat org and select clinical trials you [Music]