 Hi, everyone. Welcome to this webinar on ASH 2023, Milo-Man A. Lemiloidosis Highlights, and this is a webinar organized by Milo-Man Patients Europe, and we're really happy to have you there. I'm Solene Claveroll, and I will be the moderator of this webinar. We will start the please. Thank you. So we will start with a short introduction on housekeeping rules. Then our speaker, Dr. Faith Davies, will present her Milo-Man A. Lemiloidosis Highlights from ASH 2023. Then we will continue with a question and answer session before closing the webinar at 6 p.m. Next slide. So first I would like to give a short reminder on how to use the Zoom webinar app. Attendees are not seen or heard in the webinar, so you should be able to see and hear the presenters, but you will not be able to see or hear other attendees, and they will not be able to see or hear you. If you cannot hear the presenters, make sure your speakers are not muted and that the volume is set high. You can use the question and answer feature which is found on the toolbar at the bottom of the window to ask questions. Please use this fixture to ask a question to the presenter during the Q&A session. You can click on the like button to vote a question, and let us know what questions are of high interest to you and which one we should prioritize during the Q&A session. Don't wait until the end to ask your questions as we will try to group them by topic while the presentation is ongoing. You can use the chat feature to chat with other participants, share your experiences or comments on the current discussion, and consider audio only if you are having any troubles with poor video or if the signal is cutting in or out. So in that case, you can consider attending in audio mode and bypassing the video. If you are experiencing any technical issue, please let us know about it using the chat, and one of my colleagues will try to assist you. Do not use the chat to ask questions to the presenters, but use the Q&A function for that purpose. If you don't see the toolbar at the bottom or at the top of the Zoom window, just move your mouse slightly and the bar should appear, and the bar will disappear after a few seconds when you're using the full screen mode. The webinar is being recorded, and it will be available on our website, www.mpurop.org, and through our usual social and media channels. At the end of the webinar, please help us improve our future events and share your thoughts via a 30-second survey that we will share with you during the webinar. The link will be posted on the chat. Then we would also like to better understand your motivations to attend the webinar, so please answer this short poll. Your responses, of course, anonymous. You can choose all that apply if you are here to hear about new developments in myeloma treatments or if you are here to hear about new developments in alamyloidosis treatments or to ask questions about myeloma and these treatments in general, or about alamyloidosis and its treatment in general, or if you want to ask questions regarding your own medical conditions or if you have any other reasons to be there. I will leave a little bit of time for you to answer. We'll have an insight on why you're here and also to better set the agenda for our future webinars. It seems that half of the audience has answered the poll, so we will wait a little bit longer. Most of you are here to hear about new developments in myeloma treatments, so I think we can now end the poll. I hope everyone got the opportunity to answer and share the results with the audience. Great. Thanks so much. Just one last thing regarding that poll. The webinar itself is intended to provide information on and discuss about clinical research results that have been presented at ASH, not to provide any personalized medical advice, so please consider this when you're asking your questions. Now we will speak about ASH. Next slide please. ASH stands for American Society of Hematology. It's a professional organization representing hematologists. It's been funded in the late 50s and its annual meeting is held every year and attracts more than 30,000 attendees. It's a four-day meetings with several educational programs, lectures, symposia and scientific sessions. The meeting also features oral and poster presentations that contains new developments in scientific research. The 2023 annual congress was the 65th one and it was held last December in San Diego in the United States. We have organized this webinar to share with you the highlights of the conference so you can ask questions related to the latest results in the myeloma and alimiluidosis field. I'm very, very pleased to welcome our speaker of the day, Dr. Faith Davis. Next slide please. She's director of clinical myeloma programs at the NYU Langone Health Permutor Cancer Center in New York in the United States. She's a hematologist, oncologist and a researcher. She has a strong expertise in clinical research and a deep knowledge in the field of myeloma and other blood cancer. She has focused on the biology and treatment of myeloma for several decades and her work has played a key role in the approval of different hematology drugs. Her research works has been published in multiple scientific papers and top journals in the field and she's also part of the IMWG, the International Myeloma Working Group, which is a very prestigious organization establishing diagnosis and treatment guidelines for myeloma and publishing clinical practice recommendations for the management of the disease. So thank you so much, Faith, for being there today and for dedicating some of your precious time to MP. The floor is now yours. That's lovely. Thank you so much and good evening everybody. So the observant amongst you will realize I have a British accent and so prior to moving to the US I was practicing in London. So I'm very familiar with both the European side of things as well as the American side of things. So let's see if we can move the slides. I've kind of divided my highlights into a number of different groups and the first area I wanted to start off with was for newly diagnosed myeloma patients and essentially the big question that's surrounding newly diagnosed myeloma patients was really this year for those patients that are eligible for a transplant and should we be using anti-CD38 antibodies as part of their regimen? And so those are the antibodies such as daratumumab and isotuximab. Before I get into that I just wanted to mention a couple of things because as I go through this I'll be talking about different kinds of clinical studies and I thought it was maybe important to get us all on the same page to begin with. When we're doing clinical studies we talk about them in phases and there's actually three phases of clinical studies. Needless to say I've forgotten the first phase on this slide but the first phase is when we're really testing a new drug and for that study it's usually tested in patients who've received lots of myeloma therapy before because we're not quite sure whether the drug will work and we tend to look at that in just a small number of patients to see if the drug is effective. We then go on to what we call phase studies is where we use drug in a bigger group of patients. We really determine exactly how effective the drug is and how safe it is and then the final lot of studies we do are called phase three studies and that's where we do a randomized study so patients will get a computer will decide which treatment the patient gets and the idea here is to determine whether one drug is better than another and usually for drugs to get approval they have to go through all of those different phases of the studies and then the results are looked at by the European Medical Establishment to determine whether that drug is appropriate for European patients and so a number of the different studies I'm going to talk about today are at those different levels of where the studies are and so the first ones I want to talk about are these studies for newly diagnosed patients where we're looking to see if we can improve on the current standard treatment for these patients now for patients that are maybe a little bit older or who are not heading towards a transplant we've already discovered that having one of these monoclonal antibodies in their treatment is a good thing and so many patients will have the combination of daratumumab with lenalidomide sometimes called Revlimid and dexamethasone but for newly diagnosed patients who are heading towards a transplant there's been lots of discussion and debate about whether we should be adding those treatments in for these patients as well and I think the key here is at the moment potentially depending where in Europe you are the usual treatment for patients heading towards a transplant might be botesamib or Velcade with the lidomide index methasone or indeed botesamib Velcade with cyclophosphamide index methasone or potentially botesamib or Velcade with lenalidomide or Revlimid index methasone and in the US a study has previously shown that adding daratumumab into this combination was very effective but in order to be able to do that in Europe we need to have that phase three study to show that the combination of daratumumab with the botesamib the lenalidomide index methasone is better than the combination of just the three drugs on their own. Now for our listeners in France they've already taken part in a study that was called Cassiopeia that looked at the combination with the lidomide but the data that got presented at this year's hash was looking at the the drugs with lenalidomide and this particular paper caused a lot of stir and was one of the main papers in what we call the is where the results have just cut hot off the press. So all of our studies get named with different names so this study is called Perseus and it's a European study run in many of the European countries and as I say essentially what the aim was was to compare our kind of standard three drugs against the four drugs and so patients were able to have the daratumumab in kind of all the different portions of therapy that they may require so prior to their transplant potentially as a consolidation after their transplant and then during their maintenance therapy and Professor Sonnevelt was able to present this data and essentially it was a very large study so we've got over 300 patients in the two arms and these patients are very very typical of newly diagnosed myeloma patients so some of them did have some myeloma outside of the bones and some of them also had what we call these high-risk cytogenetic features these features might suggest that patients potentially do worse with therapy and the kind of key results of this was that for patients who had the four drugs so they had that anti-CD38 monoclonal antibody added in those patients had a much better response but not only did more patients have a better response the actual responses were much much deeper and we're going to come to this concept of MRD or minimal residual disease shortly but essentially as I say patients who had the four drugs had a better response and importantly those patients had an improvement in the time without having any disease and then these are what we call survival curves and this is a measure of how long the patient stays without disease and you can see that here we're looking at up to 48 months and at this time point you can see that more patients have a disease free with the four drug combination and I think one of the other important things just to note for generally for patients is that over the years particularly the last five or ten years the number of patients regardless of their induction treatment that are being disease free at four or five years is actually increasing which is a great thing for patients importantly we always want to know that okay it looks it looks better but what about the side effects and the side effects seemed pretty similar between the two groups and they were very much the ones which are typical for patients so low blood counts be that their white cells or their platelets or infections and temperatures I did just want to mention a quick note just as we're going through this unfortunately a few patients did die from COVID-19 which and it happened equally in the two arms so it's obviously an issue that myeloma patients are pretty particularly prone to and I just wanted to encourage everybody at this point to go and get their updated vaccine because COVID is still an issue all around the world and the best thing we can try and do to protect ourselves is by using the vaccination so anyway back to this particular study so essentially what the data suggested was that the four drugs are probably better than the three drugs when we use it for induction and they're actually moving forward maybe rather than just having patients on lenolytomide or revlimid maintenance we maybe need to think about using the two drugs so the daratumumab and the lenolytomide so this caused all sorts of stir because it could potentially be a big step forward but obviously before this can be used routinely we need these drugs to pass through all of the different regulatory authorities and so there's going to be lots of discussion about the benefits versus the costs and so on just along no lines there was a second study that was presented using a slightly different combination but with the idea being very similar and this one actually had one of the plenary sessions at Ash so that was essentially it was one of the very top abstracts that were presented now I mentioned minimal residual disease a little bit earlier and if the way we think about this is when we measure patients blood in the clinic we can measure their M component or their para protein and that's the bit we can see easily but we know that even when we do treatment patients have a lot or potentially a lot of disease that we just can't see and we often call this the iceberg effect in the fact that patients have a lot of disease that we can't see and so when we're measuring this we think about this as being what we call minimal residual disease i.e disease that we can't see but that we can measure with very very sensitive tests and we can measure this down to being able to find one myeloma cell in a million okay or one myeloma cell in a hundred thousand so very very sensitive and the reason this study was so interesting was that rather than using our traditional way of assessing how good a drug is that is looking at response rate or looking at the time patients have been disease free what this study used was a measure of how deep the responses were and this is really key for us because if you think back to the last slide with that with that new combination at four years many patients were still alive well and disease free and if we really want to bring drugs to benefit patients much quicker we need to have a much quicker readout we can't be waiting until at least half of the patients who've been receiving the drug their diseases come back which is the way we do it at the moment so we need to have better ways of measuring which drugs are effective so that we can get them into the clinic quicker and so that was the idea behind this study so in this study again rather than using the Bortesimib or the Velcade the investigators who were were mainly based in Italy were using carfilzimib or caprolis which is a cousin I guess of Bortesimib and then they used the other CD38 monoclonal antibody isotuximab but as I say the important thing was that all the way through the study they measured this depth of response with the really sensitive test and again patients very similar between the two groups a large study 150 patients in each group but the key thing was that for patients who received the four drugs their disease reached a much deeper response than those patients who received the three drugs and importantly this was at the one in a million level and really very impressive that like nearly 70 percent of patients at the one in the million level were we weren't able to see any disease in those now it was a very early abstract so they don't have any data to show the how how that translates into survival but the assumption is that using this test will be a what we call a surrogate marker for survival and actually there's a meeting coming up in spring time with the FDA and the EMA really discussing whether moving forward we might be able to use this new test of measuring how good the responses are as a way of getting drugs available for patients quicker okay so I think I just summarized that to say that it was a good study and can we use this moving forward okay so the other there was all sorts going on ash and so I've just tried to pick out some of the good bits if I've missed your missed anything then we can chat about it in the questions but the other area that was very important was around the new drugs in the bispecific antibody area and within CAR T cells and so these are mainly at the moment for patients with relapse disease and the kind of questions that the doctors are asking I think are actually very similar to those that patients are asking so which is the most appropriate way should we be using a CAR T cell should we be using a bispecific antibody or should we be using what we call an ADC antibody so that's something like the Lanternab okay and if we're going to use these which order should we be using them in should it should it be a bispecific first followed by a CAR T or an ADC how should we determine which is the best way to use these and then importantly there is actually a number of different what we call targets different things that these drugs recognize and this are a specific order that we should be using those in as well and I think one of the key things that cause lots of discussion was how do we make these more accessible because I know that many patients have been hearing about them both in Europe and the US and the rest of the world but can't actually get their hands on it so how are we going to move that one forward and then the final bit that was that there was a lot of discussion around was okay we know how good the clinical trials were but what happens in real life do we get the same kind of answers in real life and so there was a lot of different publications around people's experience of this in real life okay and the reason this is important is that we know to get into a clinical trial you have to meet many entry criteria so you have to be ill enough to get in to receive the drug but not so ill that you're for instance you have low blood counts or your kidney tests aren't very good or that your actual fitness isn't very good and one of the other things is that clearly if you to go into a clinical trial you need to live somewhere near where the clinical trial is going on and so there's actually now an estimate about 70% of patients will never be able to get into a clinical trial because of a combination of those things and so it's really important for patients for doctors but also for our regulatory authorities and our payers to know how these drugs kind of managed in the in the in the real world and essentially what all of these studies suggested particularly looking at to Clistamab which is one of the BCMA bispecific antibodies was that the real world experience was actually very similar to that from the clinical trials that the side effect profile was very similar and so if you remember some patients can get this unusual side effect of what we call cytokine release syndrome or CRS and that results in it can result in temperatures and a drop in the blood pressure and some unusual symptoms and but the the incidence of that was the same as the clinical trial it was very manageable the only slight change was that maybe the response rate was a little bit lower so in the clinical trials the response rate was about 70% but in these studies it was somewhere between 50 and 60% and the thought process there was actually many of the patients who were going into these kind of everyday practice had actually had a lot of treatment previously and also had a lot of other kind of medical conditions Now one of the kind of reasons that patients haven't been able to access the drug is because of a cost reason and because that the way the drug is given at the moment be it the to Clistamab or indeed any of the other anti bispecific antibodies is that they need to be given in hospital and that's a 10 day stay which puts the price up a lot but also makes it very inconvenient and so there were a couple of publications about how people had actually been moving this from looking at patients as an inpatient to doing it as an outpatient and essentially what this is just data from the Mayo Clinic but essentially what they were able to show was that as long as you have a good infrastructure so that patients can be looked after and go to their daily infusion visits but also have care out of hours so for instance if an issue occurs at night that they can get access to medical care quickly as long as you could do that there weren't any safety concerns about giving it as an outpatient some patients did still need to come in and have it as an inpatient but they tended to only stay for two days rather than the 10 days and importantly patients found that it was much better than then have coming as an inpatient and this little graph the idea of this little graph is it's time along the bottom and you can see that the majority of patients with actually spending less than an hour in kind of their treatment rather than the 10 days previously so a win-win for everybody. One of the important things I wanted to talk about was about infections okay because it was quite clear and again a lot of different studies talked about this that even though these new treatments are incredibly successful in inducing remissions and getting the myeloma under control they do come with a side effect and the side effect is infection okay and so this was a study from around the US 230 patients and they looked at how many patients got infections and you can actually see that 62 percent of patients got some infection and sadly some of these infections actually resulted in in death which is an awful thing when you think that some of these patients actually their myeloma was doing good but sadly they died from an infection and so this has resulted in all of the doctors being much more aware of infections now in patients and potentially for some patients we now give a number of different kind of prophylaxis for infections that could be an infusion to help bring a patient's immune system up or could be tablets to stop them getting bacterial infections and so on and so forth but I wanted to make everybody aware of that because I think it's so important moving forward that both patients and their doctors know of that infection risk okay what about other new things we've talked about CAR T cells in the past there's many new different CAR T cells coming through there's some that are called armored CAR T's where they've changed the structure of it and it's much more difficult for the body to reject it there's lots of new targets and so there was a number of different kind of publications talking about their experience of CAR T's and so I think over the next year or so in addition to the two that we currently have available there's going to be a number of new ones coming through and finish my little spiel before we take questions talking about some emgus and some smoldering okay because I think there were a couple of interesting things that came up from there now I don't know if we have any colleagues from Iceland listening but there was some amazing work coming out of Iceland so as everybody knows Iceland is a relatively small country and doesn't have a lot of immigration or migration and so they have quite a kind of controlled population and about five years ago they undertook this incredibly innovative study where they said okay we screen for breast cancer we screen for colon cancer why on earth do we not screen for blood cancers and the questions that they they so they decided they would start screening for blood cancers and the kind of questions they were asking was is this a cost effective way if we find out that a patient has a blood disease early so let's say we find out a patient has the monoclonal gemopathy of uncertain significance emgus and they don't have myeloma yet does it make a difference if we know that they've got it will it affect their long-term outcome and if it does make a difference what about the patient's kind of psychological well-being is it better to know that you've maybe got something that may or may not develop into a cancer or is it better to not know so they actually have screened about 75 000 individuals looking for myeloma smoldering and emgus and following them over a number of years and I just wanted to highlight two studies that they presented at this year's meeting one was about patients risk of having a thrombosis so this could either be a a what we call a deep vein thrombosis so that's a blood clot in the leg or could be a blood clot in the lungs and essentially what the investigators showed was that patients with monoclonal gemopathy so mg us had an increased risk of getting a blood clot they couldn't quite figure out why they thought it might be due to the level of the protein in the blood but that wasn't the case and so they said that yes they need to do further studies but the important know about this increased risk of blood clots so that if the patients were having an operation or were going flying somewhere they knew about their risk and they could be proactive about either wearing flight stockings or asking the doctors for some blood thinning drugs the other thing that they released this time was the study looking at what the psychological impact of knowing that you may have mg us so as you know about for every hundred people that have mg us one patient may go on and get an active blood condition every year and so that means that 99 patients actually nothing is going to happen to them and so they did a very clever randomized study where they let patients know what was going on or indeed they just didn't let patients they didn't tell patients the results and then they went on and did a number of tests to see the patient's general well-being and the conclusions of their study was that it was very feasible to do this that actually there was no demonstrable harm to letting patients know what was going on as long as you did it in a very detailed and balanced way okay and that actually this may be helpful in the long run and so they're still collecting data but I think one of the take-home messages is so far in their studies it's actually suggesting that maybe we should be thinking about screening patients moving forward in the idea so that we know which patients maybe have a problem and therefore we might be able to stop them developing full-blown myeloma. Now the last study I wanted to talk about just briefly is a kind of longer similar line which is kind of what can patients do to potentially help themselves and Dr Irvi Shah is an investigator who just works up the road from me actually in New York at Memorial Sloan Kettering and she has an interest in diet okay and how your diet can affect your myeloma care. Now we know that obesity and diets that don't have a lot of plant-based factors patients who have that are increased risk getting in the first place and if they do get there an increased risk of moving forward and developing myeloma and so she performed a really clever study looking at whether a plant a plant-based diet could help and make a difference and so patients were enrolled in a study for 12 weeks and they were actually given food they could choose which kind of food off the menu but they would give coaching about from dietitians about the best way to eat and the aim of the study was to see if it was feasible and what happened to patients quality of life and essentially although it was only a small study 23 patients Dr Shah was able to show that the patients quality of life improved that a number of the patient's symptoms such as shortness and breath and fatigue improved they lost some weight and their body mass index got better and in some of the blood tests they actually had a tantalising improvement potentially in some of their myeloma markers and so she's now taking this into a bigger study really to see whether changing patients diets could help so I'm going to stop there there's quite a lot of different information to take in but I'm very happy to take questions and to see what people thought about that so I'm going to stop stop sharing my screen hopefully okay and then I can hopefully see Celine and team and we can have a chat thank you so much Faith that was a very good presentation I learned a lot and I hope the audience learned a lot as well um let's move to the question and answer session um I we have a number of questions already so I hope we'll have to we have time to answer them all um and I guess everyone um knows well how to use the future so I don't need to remind people about that um so maybe so I obviously have a question around Ehle Milouie does this but maybe we should go like chronologically starting from the first um the first rise you told us about um so there was a question two questions around the cost of the four drug combination that you mentioned in the pursuit study so how do you think that's gonna that is gonna look like in the european health care systems and if it's gonna vary between different countries yeah no I and I think that is going to be one of the the key questions okay um and it's very much a a balance as I think as everybody knows that when when we take a drug to the european regulatory authorities we need to to show that it that it's effective but it's also cost effective and so as part of that whole work we need to be able to demonstrate that how patients quality of life changes um and um how potentially the way we use the health care system changes and so I think one of the the questions moving forward is to some extent going to be how long do you carry for during the maintenance period because to some extent um if we um both from a patient's perspective but also from a payer's perspective nobody really wants to be on drugs for a long long time okay um and particularly as survivals are getting better you know the answer is do we want to do maintenance for two years for four years certainly we don't want to be doing it for 10 years or 20 years and so one of the nice things within that study was that actually patients in the maintenance phase got the um the two drugs for two years and then if they were in a very good remission they actually dropped one of the drugs and continued on the rev limit so the the hope is that by getting patients into a very deep remission and beginning to use this minimal residual disease test to identify which patients are in the best remission we may be able to use our drugs more wisely which will not only help patients because they won't need to be on drugs longer and have the side effects but will also help us with the regulatory authorities um but I agree it's going to be um uh an interesting kind of time as everybody um battles with these different sides of discussion and I'm looking forward to MPE helping us with the battle let's see um we have a second question around the per se study do you do you know why the male versus female imbalance is um has not it is not really well preserved um I think they were more males than females um yeah and do you think that had that can have an impact on the results as well yeah so actually um my loma is more common in um males and females and um I agree it's maybe a little bit more in the per se study if we look in the ischia study there's still that imbalance and so it's probably you know about right so um yeah I don't have too many concerns about that okay thanks I have a question around MRD so after one has achieved MRD negative stages what's your recommendation around how often should one have an MRD test to confirm they continue to be MRD negative yeah okay no really great questions um and um I think as um as many of the questions as we're discovering they're questions that patients are battling with and doctors are battling with as well um so at the moment there is no set time period and certainly the IMWG and the international my loma society are working around potential guidance to help with this um I think at the moment most people are saying kind of six months okay um before you would um potentially want to change treatment but also there's discussion about actually being MRD negative for up to two years before you start stopping therapy so there's a kind of timeframe as to how often you should have the test done but also then I think a thought process is how long you should be negative before you start thinking about stopping treatment I have a follow-up question on that um do you know if liquid biopsies or any kind of less invasive sampling will become a standard anytime soon yeah so I can say I didn't have time to present that but there was a lot of data um at the meeting presented around the mass spectrometry technology um and so that is a blood test um where they can measure the patient's specific my loma marker um and it's um much more a much more accessible for laboratories because many labs already use a mass spec for doing other things but also from a patient's perspective is much easier um and there was a lot of data presented to suggest that depending on the technology used that you can actually get to very sensitive levels the levels may not be up to that 10 to the minus 6 level that the um the current bone marrow test can get to but it seems to be that for some of them you can get to the 10 to the minus 4 or 10 to the minus 5 and so one of the thought process is now is that maybe um we think about using a regular blood test to begin with and then when that when we get it negative of the regular blood test we can maybe change to the mass spectrometry blood test and then when we get negative to that test we can then change to the bone marrow um because that would dramatically reduce the number of bone marrows that patients have at the moment get I think we see a marrow going on trying to get over that thing okay well it's going in the right direction so we I guess we'll hear more about this later and uh in future meetings I'd like to move to by specifics now um would you say that by specifics are an appropriate option for frail patients um given the infection rates that that they're causing and because maybe of other side effects yeah so um it's quite interesting that um I've actually featured quite a lot of frail patients now with by specifics and the the tough the initial tough bit is those first few days when you may get those this cytokine reaction cytokine release syndrome problem I have to admit I most of my patients I've admitted to hospital for those first few days so that I can keep a close eye on them um but I'm not sure that's necessarily true um I think that the key thing um so I think patients can tolerate it and they're in my experience there hasn't been a particular cutoff or anything for age I think the key thing though is managing infections and making sure that A patients are on lots of prophylaxis and B if a patient has a problem that they go directly to the hematologist and they don't accidentally go to their primary care doctor or their GP because their GP is probably not going to be experienced in treating that kind of level of infection and would and the patient would need a little bit more support okay okay thanks I'm moving to Carti's now um do you think the new Carti cell treatments that have been presented at ash will be more available than the previous ones or not really yeah no I that so um we all desperately want these to be much much more available um some of the manufacturing technologies did appear to be um I don't know if easier is the right expression but did appear to be more generalizable and so I think um that that that's important um I think as well one of the other things that did happen at ash was there were a lot of um as going to say academic centers so the university centers presenting their experience with Carti's and so there seems to be kind of two two movements one is improving the process for manufacturing which will clearly make it more accessible but the other is actually rather than having a commercial enterprise having the universities may be doing this in the individual countries which again would make it more accessible so there's a general recognition quite how quick that's all gonna happen I don't know throughout the world really I think okay and regarding safety was there um a lot of discussion around the FDA investigation about Carti and secondary cancers what do you think about this issue yeah no that's that's a great question so um that kind of came out that that comment kind of came out around ash and I think one of the things particularly for myelomas which is a little bit difficult to unpick if that's the right expression is sadly we know that myeloma patients are already at risk of having a second cancer just by having myeloma and so we we know that and that we know that as myeloma patients go through their treatment often their risk of getting another cancer can actually increase as well and for those that have been involved with myeloma for a number of years probably remember we had a similar kind of discussion and issue about our imid drugs and so we're kind of now trying to make sure that we screen patients for um these cancers now I think on pure carti cell side of things it's one of those things and this sounds slightly rude and I'm trying to think of the correct way to say it and I'm not doing a very good job so hopefully I won't offend anybody okay but um I think that when we're using these drugs in the relapse refractory setting at that point we want to get a response and so what we need to learn to do is to get the response and then to manage this risk and to look after patients and screen patients properly for other cancers if we're going to move these drugs up to the first line or the second line then we're going to have to be much more observant about these potential risks and collect much more data to really determine where they are how frequent it is so that we can have those conversations with our patients and say hey this is a good treatment but this is the risk and then we can kind of manage those things I see thank you and regarding eligibility we have few questions and one of them is regarding the blood counts so do what doesn't mean do all blood counts need to be good or just a few of them um what what does it mean yeah no no no so when um when a patient goes into a clinical trial um usually the way it works is that we need to check to see whether they're anemic whether they have um any low white cell counts whether they have any low platelet counts um because from a safety side of things we then need to usually check to see what their kidneys are like because clearly when we're giving a new drug we need to make sure that the many drugs are either cleared by the kidney or cleared by the liver and so we need to make sure that the patient's kidneys and liver are in a reasonable state that they won't accidentally get side effects and so those are the key kind of things that um we're we're looking for when we put patients into clinical trials particularly when we don't know too much about the drug we don't want to accidentally cause a patient any toxicity because for instance their kidneys weren't working very well and therefore they held on to the drug for longer than they should have done I see thanks and within the the trials um is do you know if the ethnicity is taken into account considering that my low my is more common in the black community yeah so this is um a really key and important issue and um up till recently it probably hasn't been taken into account okay um as far as ethnicity has been concerned yes um we've always had to look about um how effective drugs are in our Asian patients because they clearly have a different um metabolism but there hasn't been too much work until recently in um in the um black population and so now there's a mandate from um the um the different regulatory authorities to ensure that we're including um those patients um and also dare I say it both drug companies and um and investigators are are really um trying to improve the number of patients that have um access to these clinical trials so that they can take part and one of the key changes in the slides that Ash this year which was a real step forward clearly plenty more step forwards need to be taken but there was usually a little paragraph or a little slot to say what the ethnic um kind of split of the patients was and I think that's a it's a positive step forward but clearly we've got many more that we need to do I see I see I wanted to talk about you know the last part of your talk focused on AMGAS um smoldering myeloma and the screening that has been done in Iceland do you know if there's any improvement towards starting um or treating high-risk smoldering myeloma and moderate risks smoldering myeloma? Yeah so at the moment that um that study hasn't looked at treatment it's really just looked at identifying those patients um there again at Ash there were a number of different publications looking at treating particularly high-risk smoldering myeloma so those patients that haven't yet developed um crab symptoms so um symptoms but are kind of on their way to it and there was lots of different studies looking at really the myeloma therapies in that setting so for instance there was a very nice study looking at the bispecific antibodies in that setting and I think the key here is they seem to work very well the question is is how long is the effect going to be and is it better to have the treatment early or is it better to wait until the actual myeloma develops and so those questions are still ongoing. Okay okay well thanks so much and maybe to finish we can address the ALMeloidosis questions do you have any updates? Yes I'm gonna say I apologize because I know there were a lot of patients um looking for information about ameloidosis so I truly apologize that I didn't have a slide on that so there was there was a lot of data actually at Ash um importantly um and this sounds slightly crazy so I apologize there was a very good educational session about ameloidosis and the reason I say that's important is that many of our ameloid patients will know this many doctors have either never heard about it don't suspect it or don't know what to do and so that educational session was fantastic and really got everybody up to speed but there was lots of stuff about new drugs so for instance most of our drugs at the moment target the actual ameloid cell and stop it producing the protein there were some updates of the two new drugs that are actually helping to destroy the protein once it's been um deposited and those updates were really continuing to show their efficacy we're clearly waiting for their phase three studies on that but those were definitely there um but there was also some new data about using bcl2 inhibitors which is a tablet in ameloid um some people may have heard of venetoclax which is one of those drugs but there's some new ones coming forward behind that and there were two very nice abstracts showing that those drugs seem to work in ameloidosis and then finally there was a one looking at CAR T cells in ameloidosis and so I think it's as usual it's all happening in ameloidosis it's a little bit kind of behind the myeloma field but many of the um kind of experiences that we've had in myeloma are now being tested in ameloidosis so um yeah I see okay and um would you say that um you know with all those new treatments or the old treatment if remission is achieved um in ameloidosis do we know if the treatment should continue or do we have any information yes no I I so wish we had that answer that's one I struggle with every day which is how long do you um continue the therapy in ameloidosis um and it's particularly important for patients with ameloidosis because often those patients have a tendency to get more side effects and I think again this minimal residual disease testing is going to be very important we know that for ameloidosis to for patients have the best um outcome from therapy we have to switch off the um the ameloid clone and if we can do that to a really really low level that's going to translate into much improved survivals so those studies are also ongoing looking at MRD in that setting to say hey can we stop if the patient's MRD negative okay well thanks so much um I'm sorry we can't answer more questions but I think Faith gave us a really good overview of of the ash conference and this is the end of our webinar um but please don't forget if you're in the audience to answer our 30 second survey to help us improve future webinars the link is in the chat and on behalf of the MP and all our attendees I would like to say really thank you Faith for being there with us today and for sharing your highlights of the hash conference and to answer all our questions and if you have any last word for the audience please uh the floor is yours no no my last words are that things are definitely moving in the right direction and I hope that I not only shared some exciting updates but also maybe some things that you know as a patient you can engage with and also ask your doctor because you're your own best advocate so please keep your doctors on their toes well thanks that's a great take home message thanks a lot again and I wish everyone a very nice evening