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

[Music] so i don't have slides i wanted to talk to everyone about what we're doing and basically to continue the story with chaji so just to remind everyone um i did train with bob kyle which is a wonderful thing to have because he is truly the grandfather of multiple myeloma and he's the one who really described all of this and he described it with a very um amazing sense of thinking in the future thinking 50 60 years afterwards what will happen and i think that every patient with mgus and smoldering myeloma is living that is living when will it happen to me when will i have active disease and i think of for every patient who has a precursor condition just like any other cancer if you see a woman with breast cancer and early ductal carcinoma inside to what we call dcis you never tell this woman you know what you're asymptomatic you don't have any problems right now wait until you have fractures in your bones and metastasis everywhere and then i treat you and you would think that that's crazy yet that's what we do right now with multiple myeloma we tell you wait until you have bone fractures anemia kidney failure and then i treat you so it's no wonder that we should be all upset if if that's the right word that we should not be watching and waiting however before we say okay well let's change the treatment we want to make sure that we don't over treat and and i think that comes again from bob kyle saying let's be careful that we do not over treat patients because many of you with mgus and small drink myeloma will live a perfectly normal life will have no problems with mgus and i usually say to my patients who come and see me mgus will be problem number 500 on your problem list think of everything else uh and then amgas will come in so how do you uh how do you think of those options how do you know when it is the time for you to really worry and do something to prevent progression and when is it the time for you to say mgus is there but i have other things and i'm going to enjoy my life and go on with my life and i think the question is how do we predict the risk of progression so with that in mind we started something called p crowd six years ago um so it's very similar to jenny's work and many others what we wanted is truly to change the way you think of research we wanted to involve every single patient and we said this is crowdsourcing but instead of money it's for patients we are opening this for everyone to be part of it uh so if you don't if you want to look it up it's peakcrowd.org anyone can sign up to it anyone who has a precursor condition mgus or smoldering myeloma all over the united states and in fact we're opening it internationally with the idea that empowering patients to be part of the research that is direct to patient access will make a difference and indeed it did six years ago we opened it up and we have over 3000 people and that made a huge difference for us to get blood samples bone marrow biopsy samples as well as clinical information from everyone to tell us what changes how will someone progress to active myeloma and what are those markers um so dr kumar already told you there are clinical markers when we sit down with you every day we can look at your m spike at your light chains at your bone marrow percentage and try to predict for you if you are going to have this risk of progression what we're trying to do now is can we improve on this risk of progression can we be more accurate and i think of it as one of my colleagues said it's like predicting the hurricane if you're looking at the weather channel you do not want the weather forecast to be there might be a hurricane coming in the northeast area and maybe it will happen in the next two weeks you want it to be more precise you want accuracy and prediction that is much more precise so that you can know what to expect in your life and we are hoping to do that to bring this accuracy to you and we know already that when dr kumar looked at the 20 to 20 model when he looked at your genomic data your own dna data it can improve on that prediction we recently looked from the p crowd samples from everyone who participated on looking at something called next generation sequencing meaning you would go deeper instead of looking at the big pieces of the chromosomes if you have translocations or um what we call one q amplification 13q deletions all of those are big pieces we went into all the way to single molecules of your dna to see if we can have better prediction and with that we found three areas and in fact mayo clinic was the first one to show one of those something called mic alterations something called map kinase mutations and something called dna repair mutations and if you have one of those it tells us that by having one of those you are at risk of progressing to myeloma and if you don't have those you may not be at risk that may not be enough we need to actually work together to improve on this accuracy and there is a third compartment to this it's not just the cancer cells it's also what surrounds the cancer cells and we're also looking at that and that's called the immune cells we know and many of you will tell us you have a lot of infections you have immune changes you have other things that are going on we know that your immune cells and the cancer cells talk to each other and we also from the p crowd samples started to look at your own immune cells and to see if they do change with progression to myeloma and can we use that to predict progression but also can we use that to treat multiple myeloma before it happens and we found in a recent paper and we're happy to share that data with everyone is that even when you're at mgus even when you're that early in mgus your immune system is not completely normal you are not completely healthy like everyone else it's not all the way to myeloma but it's definitely already changing the cancer cells are already changing the immune cells and making them behave in a in a bad way so that they can allow the cancer cells to keep growing now why is that important it's important because when we think of predicting progression we want to put all of those factors together and we want to give you that information in a more precise way so we look at the cancer cells your own clinical data the immune cells and try to give you this prediction model that is dynamic that is really reflective of who you are and then hopefully also treat you in a precise way with who you are so if you have an 11 14 translocation if you have something specific that we can target can we do something called precision medicine for smoldering myeloma and dr kumar has shown before as many other studies that indeed when we treat early with two drugs lenalidomide or revlimid and dexamethasone versus doing nothing you can't change you can't prevent progression you can prevent end organ damage meaning the kidney disease or the bone disease and so on so now we're building on this we're trying to say can we use the immune system to harness that can we do other things to also improve on treatment so that we can prevent progression and there's a whole area of therapeutics or treatments that we're all developing together so that the true answer for you is we want to make sure no one ever develops active myeloma no one ever develops the crab criteria the high calcium the bone lesions the kidney failure if we do that that's the least success we can do and then hopefully we can also improve survival and hopefully we can cure completely myeloma by early intervention by early treatment the next question i'd love to talk to you about is well what else can we do and why did i get that and it's an important question especially for people who have a lot of family members who have myeloma or wellness from macro global anemia and myeloma and you start asking the question is there something that's inherited are my family members at risk and we know from big studies that there are certain people who are at risk of developing myeloma or mgus more than others now dr kumar already mentioned a few of those being of african descent black americans have a two to three times higher chance of developing myeloma compared to the caucasians and we still don't know why we're still working on that and in fact dr kumar and i have really a strong interest to understand this more we know that if you are a patient you have amgas or smoldering or myeloma or amyloid your family members may also be at risk two to two times higher chance of developing myeloma and the biggest question that we have is of course as we get older we are all at risk so the age is also an important factor as we get older we have a higher chance of developing mgus and the question is if we don't look for it we don't find it and we will never diagnose it early until you have symptoms until you go and get the bone pain or the fracture and then suddenly you have myeloma so why can't we look for it if we can prevent it and make a difference and we know that cancer screening saves lives all of us will go for our mammogram and colonoscopy and psa although a lot of people have questions about that you want to detect cancer early to prevent progression you want to find it early so that you can do something about it so with that in mind we started another program and again it's nationwide it's online you don't need us as physicians to be part of that and that's called promise so promise study.org and i'd love to have everyone online right now google it while i'm talking promise study.org and you can see that it's simple you answer three questions and you can see if you are eligible or your family members are eligible or not and with that again we're asking for one blood sample to see if you do have mgus or not and we're using a very sensitive new test that has been developed by mayo clinic we're working with mayo again on this one where we do something called mass spectrometry to see if you have a little bit of this mgus and if you do can we be uh preventing it early can we understand what causes it and why did you develop it that early and who else is at risk and potentially prevent progression to myeloma and then the last thing i'm going to tell you about and i know i speak very fast uh is a new study and it was actually inspired by jenny and we haven't opened it yet but hopefully it will open in the next few weeks it's called the impact study and the whole idea was we know that covet 19 is here with us for the next year at least and we know that vaccinations are coming in yet we don't know if you have mgus or smoldering myeloma are you at risk just like someone who has active myeloma and you may actually have a worse prognosis we know that there is some data that says myeloma patients did not do very well with covert 19 infections are you going to have a good response to the vaccines when they come out will your immune system be sustained when you get a vaccination to covet 19 and all of those are questions of if i have mgus or smoldering myeloma and i know that my immune system may not be working so well but it's not completely abnormal what is my risk of covit and what is my risk of vaccination and how will i fair with the vaccination so with that we're starting a study called impact and it will be open for anyone who is on p crowd or promise so you have to be a p crowder or a promiser to be part of impact and again it's online you sign up to it and we test you for coven 19 antibody we give you back the results uh through quest diagnostics and then we do for you immune cell sequencing we look at single cells from your blood to see if your immune cells are going up or down are responding well to the vaccine or to covet 19 and we're hoping that that will launch october 1st um or at least the first few weeks of october so please be on the lookout for impact so again all of this is truly efforts to change the way we think of emgas and smoldering myeloma to really diagnose it early prevent it early potentially cure it if we can diagnose it and prevent it early and change the way we think of waiting until people have active disease until they are falling apart like dr kumar said and then we treat it and it's only by the power of patients by people like you by jenny by many people who can make that difference for us