(Guest Lecture): Audience Questions & Answers | HealthTree Foundation Round Table on Genetics

[Music] but we want to thank our roundtable sponsors who made this series possible that includes amgen oncology takeda oncology glaxosmithkline janssen oncology genentech sanofi genzyme adaptive biotechnologies carrier farm therapeutics bristol myers squibb and foundation medicine okay with that i'm going to start with an emailed in question um and it's kind of a hard one it's high-risk newly diagnosed high-risk smoldering myeloma patient and dr davies and dr van ness you can unmute yourselves as well newly diagnosed patient considering i know that we talk about smoldering myeloma patients joining clinical trials if they're going to go through treatment but he has the 1114 translocation so in a situation like that where you have a drug like venetoclax what do you do do you join an ascent trial or another high risk smoldering myeloma trial do you consider using 1114 venetoclax up front i mean you know if if it's highly targeted for that with no other genetic features what do you do because logic okay not that myeloma is ever logic logical but logic would tell you that the the smoldering myeloma is being driven by that 1114 translocation and so therefore logic would tell you that if you were able to target that specifically then that ought to solve it completely so a little bit like in cml where we have the drugs are very specific to the translocation in cml um the problem in myeloma is it's very rare that it's just that one translocation and there's lots of other things that are also going on um on and around and about and somebody mentioned the really nice work that irene is doing up in boston about characterizing small dream myeloma and her study shows that yes even though many of those initial translocations are there driving the disease there's lots of other things that are going on as well and we don't quite know what for an individual in patient what the weight of each of those things that is going on is doing so i think the the safe answer if that's the right expression is that if you're a smoldering myeloma patient then you hey i think it's really important you're seen by an expert because we really one of the things i think that at the moment is key for smoldering patients is to get in there before the myeloma takes off or gives any kind of bone disease or anything so i think that's key but then if you are going to go for a clinical study or are going to go for treatment then i would recommend it was in the clinical study if there was a for if there was an 11 14 clinical study out there then yes i put myself in it if i was able to do it yeah yeah i don't think there are into the higher small in the smoldering malama setting but for that translocation but yeah so interesting dr alawadi do you have any thoughts about treatment yeah i think i i completely agree with what uh faith has said so i also i guess so actually i was running in the hospital this morning and i have a patient where i was having a similar discussion about 11 14 and uh this patient does not have 11 14 mutation but they were really interested in somehow getting uh venetoclax and they don't qualify for the clinical trials we have so so what i was explaining to her and i think that does apply to this uh individual's question is also unlike cml where cml has a particular mutation and every single person or majority of the people who get treated with those targeted drugs in cml they respond what was seen in what has been seen with the venetoclax studies is that clearly 1114 or bcl2 high expression patients respond much more than those who don't have it but it's not nearly as universal as for example is seen in cml and that exactly goes back to what uh like faith mentioned or what irene is doing unfortunately in myeloma it is never so cut and dry that's one single mutation driving everything so i think having this discussion is important looking for the trial is important absolutely so yeah there's another thing jenny it was just a quickie and i thank jack for highlighting it that what particularly what we've been talking about today has been the risk genetic risks of myeloma they're not necessarily the same things that drive a smoldering patient to move from myeloma from smoldering myeloma to myeloma and i think that's important to know so the good example is that 1416 is not meant to be such good news in myeloma but sometimes in smoldering myeloma it can actually be a good thing so i think we just have to make those two a little bit and dr van ness do you have thoughts about this yeah let me let me just comment that if you now look at the biology and say that the um translocation that's being discussed in which this gene bcl2 is overexpressed go back to the biology what is bcl2 well bcl2 is a gene that stops cells from dying so you've got a function there that you've got to get rid of because you want to kill the cells but it's not the only gene that stops cells from dying there's a gene called bcl x there's another gene called mcl1 and it turns out that in some studies we've done with the mayo clinic in scottsdale it appears that if you don't respond to venetoclax it may be because you are over expressing one of these other genes that stop the cells from dying so what's the solution drug companies are making drugs against bclx and they're making drugs against mcl1 so now there is a panel of drugs and you could imagine that if you test a patient and says bcl2 is overexpressed okay we're going to use venetoclax because that's been demonstrated but if you've got mcl1 over express then amg 176 is a drug that targets that so we're getting better and what's going to happen is the clinical trials are going to have to start developing these kind of stratifications to demonstrate that choice actually is directed yeah biology would say yeah we probably have some good reasons why we ought to start thinking about directing those therapeutic approaches based on either a genetic or a protein characterization of the tumor and he had high b cell one so that was interesting like in and so does that does that even work i don't know that would be interesting to find out okay we had some other emailed in questions and luanna's question i think you've already answered can genetic march markers change over time and the answer was resounding yes um yani says uh and there are a lot of questions about one the one cue game so i want to kind of ask these um in in general and then maybe we can split them out into separate things so is there an expert consensus relating to the 1q gain and how relevant the number of extra copies are i know like in the compass study it was saying that if you have one q gain and you have three copies it's not necessarily considered high risk but if you have four copies um then it is and then we had some other one q gain questions about um particular treatments and dr alawadi you kind of went over that a little bit you know breaking it out by biogenetic feature but um and and yeah is is there any and then susan asked a question about the one q gain are there any immunotherapies that are particularly seen to to to do this one q game so let's talk about one queue i guess so um okay i'll go first you're probably going to get slightly different answers from each of us so there's a an old study from arkansas um um which is really good and i think has really set our the kind of the compass for the one q in the fact that you're correct many patients will just get one extra copy so they'll have three copies of one cube and that's probably you know so so it's when you start getting four five six seven eight ten copies of one cue that's when that becomes a truly poor prognostic site and it's really difficult when you're reading the reports actually and i know this from kind of a physician's perspective is that they often don't tell you how many extra copies are there um and so um so that's where some of the the confusion and that is there are researchers that are really concentrating on that one queue area because it's so it's going to say from a research side of things it's so interesting but it's also so important for patients and there's lots of kind of cancer genes in that area and people are now trying to match therapies that potentially might target um that area particularly the immunotherapies are really going after that area so i don't think there's anything definitely come out yet but it's certainly an active area and i know there was um some work presented at the big meeting last year looking at different treatments for that one cue abnormality great okay dr van ness will jump to you do you have any thoughts on the 1q game well you're asking a clinical question and and i have a disclaimer so no but i'm going to address a slightly different question with that that i'm sure is plaguing every person watching this which is you've just described four copies five copies two copies and their question is why does that happen i mean why did it happen to me um that's not a normal occurrence but what happened to make it that way um the answer unfortunately is we don't really know there was some studies done many years ago linda polarsky i think actually did some of these studies that demonstrated that there are proteins whose function it is to make sure that when cells are dividing they get the right number of chromosomes so that they split them up evenly instead of one getting too many and one not enough and there were some studies that were done that suggest that some of these proteins become a little less efficient as we age and so you might ask the question then okay this might i'm not going to suggest that it's true but at least it brings to mind oh if that's true that might be why myeloma is a disease of people that are older you don't see it in kids very often you don't see it in young adults so something is happening during the aging process that makes people more vulnerable that's a different type of risk we're talking about risk of progression response but the other risk that everybody's interested in what's the risk of any individual getting myeloma and we don't have really good answers for that partly because it's a complex disease but one of it is possibly we're getting a little less efficient as we get older in separating our dna into the right um uh proportions okay great dr alawadi do you have any thoughts on the 1q yeah so i agree that one q is turning out to be one of these uh the area within genetics which i think probably has the least number of answers and the most number of questions around it because on the one hand i shared with you the mayo criteria which by the way i can tell you that uh when i joined mayo clinic about six years ago it was kind of whispered in my ear that whenever i make a presentation if i don't touch upon i'm smart somebody's going to tell vincent and he's going to know and i'm going to get a nasty email the next day just kidding so uh you see the the mayo criteria which is saying that one queue is high risk at the same time there are some of these recent clinical trials which are focused specifically on high risk disease uh like we have now frontline car t uh treatment which actually has not included that into that category because i think one queue is still being understood and defined a little bit better so um just like uh i guess robert asked a question saying that he has a fish profile with a chromosome abnormality 1p1q and monosomi uh 13. so what does this mean for a myeloma patient so i think that's very important because what it tells us is also that if one q abnormality is present by itself it has a relatively different different significance but if it is present with other abnormalities now we are talking about that there is much more genetic instability if i may use the word and so the importance of that one cue with a different abnormality is different and i think a lot of the patients would probably be thinking just like i said well we'll we looked at this variability across the country about how these tests are done i can i can share that pain because out of those 1200 cases i helped abstract each and every single one of those reports and it's it's painful so i think what we did was that when we called all those labs one by one and said hey you've not reported the percentage you've not reported the copy numbers generally the thought the answer that we kept getting was that if a lab says that there is positivity there is positivity above the threshold for the test that is valid within that lab so i think it's important to ask those questions but we don't have a single given answer saying that okay just like in 17p we're saying or in eleven fourteen we're saying but into class or 17p we're saying well you've got to have a pi mid combo you want to have longer duration pi treatment or you want to have multiple drugs i don't think we have that answer for one queue but i have a feeling that there will be way more amount of data that will come out in december at the american side of hematology meeting this year trying to delve deeper into that one queue problem out of all the databases we have okay yeah great great answer um we have another question by richard who's and dr davies you talked about the different types of tests you kind of all address these a little bit most are bone marrow related right but the mmrf is saying that peripheral blood is sufficient for genetic analysis but dr davies you were saying it's not quite ready for prime time so what do patients do with that yeah so i'm going to say there was as you say there's been some really cool questions so um i think that's exactly it that the mmrs are working with a lab who um have developed and have access for that test which i think is really um important and is really going to drive things um forward um and so i think if you're a patient who enjoys being part of research i'd positively encourage you to not only be part of the myeloma crowds telehealth health tree thing which we're going to hear more about in a moment but also think about if you can be involved in the mmrs project or indeed the project that dr gabriel has in boston okay because all of them are driving forward the information we need for the regular patient in the regular hospital the current test is done on a bone marrow we are all desperate to move forward and have the blood test based version um and so we're all working towards that but um it's only available in in kind of the research setting and i think dr vanessa's going to add something to that this is one of those examples where doing a genome test of a whole genome was impractical 20 years ago this is this is technology evolution if you will in the technology evolution think about what you're asking you're asking i can genotype a myeloma if i take a sample of the bone marrow where it's filled with myeloma cells so i've got lots of sample there to work with now if i go to the blood there aren't very many myeloma cells in there there might be a few but you now have to have a technology that allows you to get past all of the other dna that may be there and just find that small amount of myeloma dna that might be in the peripheral blood and i would say five six years ago nobody could do it now some people have actually developed new technologies and one of the reasons they've developed those technologies is that you can keep going into the genetic testing and repeat it and repeat it and repeat it and keep getting deeper and deeper and deeper why it's getting cheaper and so the cost is driving this as well so i agree with faith it's a very interesting could be a very exciting way to do genetics and myeloma it's a lot easier on patients to get a blood sample than a bone marrow and if you can get good information from it which it looks like it's coming then it's going to be a very effective test but that technology is not available uh sort of commercially across all centers great okay and dr alabadi you were talking about disparities in karen an african american community or the um african descent community because it's not necessarily just an african-american thing are there known reasons why african-americans are or the black community gets myeloma at a younger age and then could the better outcomes be related to the fact that they're just younger when they're diagnosed excellent i think that's that's a very very good question very insightful so that's kind of going so first question which was do we know exactly why they get it at a younger age short answer is no but there are some very large uh level studies called g was or genome-wide admixture studies that have been done um actually one of the stuff one of that studies was where all of the cytogenetic and fish data came out for where we looked at the variability what jiva studies are showing are is that the the genetic so the the the markers or the genetics of a person who ends up developing myeloma even the uh the genetics which is their uh what they're born with is how i want to say there may be some different signals in the inherent genetics that a person has because what happens is all of these tests that we're talking about we're talking about myeloma cells somebody was not born with these myeloma cells they were born with a healthy uh just like uh dr vanessa explained the the chromosome makeup the 46xy the 46xx those are healthy chromosomes that somebody's born with at some way along the road at some point along the road they have acquired something or something has happened something is triggered that the healthy plasma cells are no longer healthy anymore and they have developed into myeloma so there's a lot of work being put into understanding what constitutes mgus to smoldering or smoldering to myeloma and why it occurs in african-americans or those of african descent at a younger age it seems that some genetic signatures are different but i don't think that we know that those genetic signatures are the drivers they are present or they may be associated but they may there may not be causality yet that we understand so that was uh that in my mind but there's a lot of work being done in that area in fact uh nci wants everybody to understand nih there's a lot of funding that is being applied to this particular area there's a lot of interest and jenny the second part of the question was um oh i took it out you're not finding it anymore okay it was basically if somebody's younger does it um does it mean they're going to do better just because they're younger that's a very good question and that what i said is going to the crux of how we even do these analyses so when these analyses are done and in fact there was a question i came across which was a very interesting one somebody had said well i have uh one cue or one of the abnormalities and then if i have a bone lesion does that make me a very high risk so this high risk ultra high risk very high risk those terms are more associated with the genetic markers not necessarily building in the clinical aspects there but when we do these analyses we do what's called a uh or studies typically we do what's called a univariate analysis meaning one characteristic and picking up the importance of that and then calling what's called the multivariate analysis in which they'll put in all the characteristics that came back significant they'll adjust for each other and then see which one still comes back as an important one so irrespective of controlling for age gender uh geography etc african americans were found to have a better outcome in this most recent study from 2019 and a lot of these analyses from 2017 2018 they did control for patient age so it's not that african-americans are having better outcomes now that we're finding out in an equal access system just because they are younger but i think that's a very very good question because it's asking the basic premises of well do you guys even know what you're doing or how are these studies set up because that's an important point and um michelle has a good question and i saw another question that was similar when you're in remission do these abnormalities disappear i asked dr fonseca one time can you just kill this mutation for my cells please and and he said well actually this mutation is on you know a majority of your myeloma cells or a large population of your myeloma cells so her question is when you're in remission do these abnormalities disappear and then are these chromosomal abnormalities the same thing as mutations if you think about it like that so dr van ness do you want to start with that okay so the first the mutation so i'm going to categorize mutation and we'll do that we'll do the finger quotes mutation is a term that basically encompasses all genetic changes that may occur that are not part of the normal um chromosomal content so chromosome copy number that's a type of mutation a single base change of the dna that's a type of mutation so there are lots of types of mutations and we kind of lump them all in so i would say chromosomal abnormalities are a type of mutation does that mutation or does that abnormality go away well it really becomes a matter of how how confident are you that you are able to detect myeloma cells when they get the very very very low numbers the idea is in treatment you would like to get rid of a hundred percent of the myeloma cells my genetic counseling friends would be happy if i said this in genetics you never say never you never say always and so the idea that you can get rid of every single 100 of the myeloma cells so that you can't detect those abnormalities yes absolutely if you could do that but it becomes a matter of what is the limit of your detection of those abnormalities so if you fall below your detection limit the oncologist will say well we can't find any more of those abnormalities the oncologist isn't saying there aren't there they're saying there are such a low level that we can't detect them now from a clinical standpoint that's a good result not being able to find any residual disease is actually a good result that's different than saying zero disease great and we have 70 questions so we're a little overwhelmed on our questions and we'll try to go through as much as many of them as possible but um harold kind of has a question that kind of relates to what you just said dr van ness have we found any correlation between minimal residual disease testing or mrd results and genomic profiles so dr davies dr alawadi i'll let you start with that question so i think the the one thing i would say if that's the right expression is that if you are known to have truly high risk myeloma so myeloma that's really growing very aggressively then we definitely need to try and treat those patients to the point where they are mrd negative there's a couple of studies that have been able to show just as brian was saying that if we treat those patients to the point where we can't see any myeloma left then those patients seem to do better than if we treat those patients and there's still a little bit hanging around so and that would be the one correlation that jumps out to me and stay off yeah i think uh what i can add is i i agree that so right now uh the mrd negativity is something that has very important uh prognostic significance uh in different study settings whether it is transplant non-transplant even transplant compared to non-transplant head to head it's been shown that when a patient achieves the mrd negativity or basically a depth of response and think about it this way before mrd it was cr stringent cr etc uh so when we have depth of response that translates into typically a longer duration of response i don't think and i've i've come across some cases where a patient got their induction treatment they got a good response where they could potentially be considered for a transplant but the bone marrow was done and mrd testing came back positive and their treatment was switched and said well let's get two of these rounds or four rounds of this particular regimen let's see if we can get you to mrd negativity before getting you to transplant and in fact in one case that didn't happen so the patient ended up going to the third regiment and when that also had mrd positivity persistent they came for an opinion we're not there yet we're not there to say that you need to somehow get the treatment to mrd negativity and keep driving it there there are very sophisticated clinical trials going on which will hopefully answer that question but for example one of the questions they will answer is well if you're mrd negative can you stop treatment can you stop maintenance and patients are getting randomized and stratified on those clinical trials if patients have an opportunity to join these trials please do so clinical trials are the only way we move our field forward but at this point i think the idea is if somebody has aggressive just like faith mentioned if somebody has aggressive disease very widespread very aggressive disease deeper the response better will be the outcomes but that does not mean that we keep changing the treatments to get to that depth it's that we're not there yet great okay we have a just comment by jack that suggests that somebody should clarify that high risk and smoldering myeloma is not exactly the same thing as high risk myeloma genetics um does someone want to address that issue yes so high risk in uh smoldering myeloma jack excellent point that i absolutely deserves an answer so genetic risks they apply to myeloma all across but there are some clinical characteristics which are taken into account to say whether a smoldering myeloma would be high risk or not and that is talking about not just the genetic markers but also the risk of that smoldering myeloma proceeding or progressing to active myeloma so for example having more than 20 percent involvement of the bone marrow so for example smoking myeloma it could be anywhere above 10 but those who are between 10 and 20 are not as high risk of progressing to myeloma as above 20 percent similarly if somebody has an m spike above two and they have smoldering myeloma they are considered a higher clinical risk as compared to if let's say they had 1.5 and there is also a light chain ratio so light chain ratio above above 100 we say is what is now considered by mwg is akin to treat myeloma requiring treatment but if let's say somebody has a light chain ratio of 80 and somebody else has a lightsaber ratio of 10 80 would be higher risk and it's been brought up as a the 2 20 20 rule two of m spike 20 of light generation and 20 percent of uh bone marrow involvement that if somebody falls under these those are higher risk clinical characteristics suggesting that that small ring could progress to a higher likelihood of progressing to active myeloma and these are genetics apart an excellent question i think okay great uh and there's a common question that all patients have i think you taught you'd everyone addressed a little bit about when to get tested but um and which tests to get but eloise was asking you know what tested if you're relapsing what test should you really ask your doctor for like i had to really push my doctor to do an ngs test because i wanted a more detailed test and it took a lot of pushing to get that test run and um i've had the gene expression profile test done before which is the most valuable and it should be just be okay getting a fish test and then if your doctor doesn't do any genetic testing which was on one of the other questions then what do you do do you just you know you go somewhere else and get to get a fish test done because you kind of need to know what you're dealing with right dr davies do you want to address that first and then we'll have everyone comment so i agree you need to know what you're dealing with a lot of um there are some physicians out there that because we don't necessarily use the treatment to decide use the test to decide what treatment we're going to give a lot of physicians will say oh well you know i don't see the point in doing it okay and i would argue that you're going on a journey with this um myeloma you need a good map of your journey okay and i agree at the moment we try and give the best treatment we have to each patient but as we're discovering certain treatments do do better for other patients and we may not use the information today to guide the treatment but we may use it in a year's time things are moving so quickly the three tests you mentioned each give us slightly different information okay all of which is important um i used to work in arkansas so i love the gene expression profiling test okay i'm not sure it's particularly available in a clear defined way in the us at the moment i know in europe um there's a slightly different version by sky diagnostics which is being developed um but um it is i don't think that you can get it in a kind of clear which is the posh term for kind of approved in the u.s at the moment so i'd say the minimum you should have is the fish test if you can also get the next generation sequencing test done as well i think that gives us lots of really good additional information um so if you can get the kind of that then that's great but at least the minimum is there is the fish test okay and then does anybody else wanna well weigh in on that topic i'm gonna i'm gonna do this more philosophically and that is we are talking about individualized medicine we are talking about personalized medicine and i tell a lot of patients that as we discuss that personalized and individualized medicine also means there is an increase in personal responsibility that is if you truly want personalized medicine then you have to personally invest in learning as people are doing and watching this and pushing your position to say i want to know about me and so there's personalized medicine means personalized advocacy and i do see that the advocacy by patients it's remarkable to me how much patients know and the questions we get indicates they know a lot and i don't know faith does that scare you that a patient comes in and knows so much and it starts telling you what they want it doesn't scare me it makes my conversation so much more enjoyable so it looks good i love it and i was going to say i think i think i could totally agree with you um that patients asking for things don't be frightened to ask ask and and see where you get because sometimes it's just that the physicians haven't even thought about it so and i think jenny i want to kind of add to that i agree that it actually makes the discussion very um enjoyable and also it makes our job a little bit easier because we know that that same que patient who's asking for the the particular kind of test is going to inform us when they have the peripheral neuropathy or when they have a blood clot that is telling us that the patient is involved in their own care so it makes actually our job way easier but i would also say we unfortunately come across these examples where someone will say well we're going to get vrd anyways why bother doing test x y or z or etc so uh there's a study that was presented which so far is the only dedicated high-risk myeloma trial prospective clinical trial that's been presented it was presented at the asco meeting just last month which was a national cooperative group trial and it's very commendable that the national study was done only focusing on high-risk patients and believe it or not the study was conceptualized in 2012 and it was completed accrual was completed almost four years ago but the data could not be presented because the good part was that not enough people progressed which was excellent which means something was happening right that primary plasmas are looking at 17p deletion 1416 1420 1q people were doing better and main reason was because everybody obviously knew what the testing was it was vetted by the study team and then patients got a combination regimen by the way the in the study both the regimens both randomized regimens did pretty much the same one was not the winner but patients got their treatment for an extended period of time and then they got multiple agents for maintenance for an extended period of time so i think that study has informed us how to treat high-risk myeloma better but we can only do that once we know who has high-risk myeloma because by all means we're not going to be treating every single malama patient with three years or four years or five years of vrd without those modifications etc so so i think it's important to know we need to know what's the abnormality and that's why we can actually tailor the treatment better because it's not only the choice of drugs it's also the duration of therapy the type of maintenance all of that has to go into that decision well i totally agree with that yeah but one one other point and that is that every time you do one of these kinds of genetic tests and if at day one you get the results you can interpret it as dr davey said you might be able to interpret it a year later why might you be able to interpret a year later because 200 other people are getting genetic tests that have similarities to what yours is so the important part of this is we're collecting data and the more people that contribute to the larger database the more we're able to make specific correlations between a genetic event and an outcome it doesn't work if i only have one sample it works a whole lot better if i have a thousand yeah i i totally agree i attended a myeloma patient seminar when i was first diagnosed it was probably 2011. and i i asked there were probably maybe 300 people there and i asked everyone to raise their hand if they had had genomic testing done or if they knew they're my loma genetics i would say less than five percent of people raised their hand and it just made me think well and kind of the philosophy at the time was like well we're not going to treat any differently but it's like if you're not capturing the information and then you get treated and these genetic features go away then you have no idea what you were dealing with in the first place and like what you're saying it's just gonna inform us later kind of along those same questions i saw a couple questions about non-secretory myeloma where you're not producing this monoclonal protein to measure so you have to do these bone marrow biopsies instead or light chain only myeloma are genetics different in any way for those types of myelomas uh or are they just the same that you're talking about is there any difference that you see like a pattern that you see in light chain only myeloma genetically or non-secretory um i'm just trying to think off the top of my head there's a few subtleties but overall not particularly so like light chain can often have um more and can often be more of an iga and can maybe have more 414s um so there's some subtleties and differences in the numbers there but the overall kind of picture off the top of my head is is the same okay there are there are some just like was mentioned there are some subtle differences so i used to work in uh los angeles before uh coming to mayo and uh we noticed for example that hispanics which we had a lot of in in los angeles the uh the incidence of light chain only myeloma was way higher than what we knew historically and primarily because we didn't even have a hispanic enriched data beforehand so i think there are some subtle differences clinically they are a little bit different and and by all means non-secretory myeloma which is where a patient does not have any serum as in blood urine and spike or even light chains that are high enough to be counted as measurable disease and so this non-secretory myeloma does pose a problem because unfortunately at this even despite all of these uh developments we're talking about majority of the clinical trials do not allow non-secretory patients primarily from the reason that gauging response to treatment is very tricky you may require repeated pet scans or repeated bone marrows and it becomes very difficult but the bottom line is that we still have patients like that and we still have to figure out how to manage them well okay um there are so many questions i'm having a hard time uh choosing them maybe i'll go to paul's question because he had a question about the 1420 myeloma and um yeah i'm i'm a 1420 myeloma person at diagnosis anyway as well and at the time there were maybe five percent of patients three percent of patients who have that genetic feature is there anything we've learned about that and also someone had a question about the deletion one which is not that common do we know anything about those two specific genetic features so um 1420 there's um a really nice um paper that came out of um the atlanta group from emery and recently discussing that um it um is seen to generally be or potentially be a poor prognostic factor but as you are beautiful proof of it not everybody um it's so it's not just that translocation it's what hangs around with it and what goes with it which is um the kind of key and i think that's would be my take-home message for all of these things it's not just the one abnormality it's what else is going on on there and that accounts for the 1p as well because um in many studies the 1p is found to be um poor prognosis when it's deleted but again it's um maybe doesn't have quite as much weight as some of the other things but it's what happens with it that's the key and i think just generally and um this is where i'm not a mayo doctor and so i'm probably going to be shot down here but that's one of the reasons why for me the m smart criteria it does work but it needs to be taken in the wider context because in that criteria they just talk about each individual abnormality and i think you need to think about the whole rather than just concentrating on one thing and then yeah double hit right when you're talking about double hits or things like that yes exactly so i think we have to start thinking about adding them up and actually jenny i'm i'm sending out message responses some of the i'm just typing out some of the responses to patients and this is just coming up like just like faith brought up that so while we have lumped these five abnormalities together and we've said high risk it's important to understand that the mutual contribution to the risk of a myeloma may be different so for example what if somebody has just one abnormality which is deletion 17 and a different patient has just one abnormality of 1q amplification while they or for that matter let me make it less controversial and i'll take the mayo piece out of it but let's say uh uh 1416 okay let's or 1420 we just talked about it so let's say one patient who has an isolated transportation 1420 and a second patient who has an isolated deletion 17p now both are considered high risk but are they both equally high risk because when we bring it down to a patient what is the importance to that particular patient that's what when brian mentioned that we have we're talking about personalized medicine we're talking about individualized medicine i don't think we fully understand the mutual importance of these uh each individually if one occurs with another one so there was a nice study at ash last year which actually talked about the mutual combinations of these high-risk mutations and what that may mean but you can imagine we need so much more data where we have enough numbers of patients who have single mutations double mutations triple mutations out of these normal or standard work plus high only standard only high etc and then we'll hopefully get to that point i mean i think we will get there i think we are slowly and gradually getting there but it's important to then bring in this discussion at an individual level with your doctor and i really think that a patient who has any high risk features i think it's very very reasonable to seek out a myeloma focused person i'm not saying necessarily in malama expert because that could be relative but a person who focuses on myeloma please seek out an opinion just get an opinion go back and get treatment with your doctor but at least hear that thought process listen to these webcasts you learn way more yeah i think that's a great um a great place to to stop with the q a we have a lot um i will be showing a little bit about health tree oh dr van ness did you have a comment i do have one conclusion concluding remark on all of this and and uh dr dr davey's uh clinical partner gareth morgan and i get into this argument all the time and the argument is that there are certain genetic features that define high risk and as dr morgan has said it was high risk five years ago it was high risk 10 years ago it'll be high risk five years from now that's where i disagreed with them and the reason i disagreed with them is the reason it's high risk is because we don't have a therapy that targets that particular risk group good example deletion 13 was always viewed as very high risk but it turns out they did pretty well with proteosome inhibitors so it fell off the high risk group so i think our future of myeloma treatment is to identify effective therapies that one by one keeps knocking off the high risk characteristics so that a genetic profile is done in a patient and they're considered with the available therapies standard risk and we know how to treat it great that's a that's a perfect concluding comment because the more we know the more we're going to know it's so it's so exciting yeah dr van nessa and dr davies and dr alawadi you're just so amazing when it comes to this topic and we can't thank you enough you