welcome welcome everyone to this uh post as uh uh video uh conference uh the imwg uh conference series um thank you for joining us today and I'm very very pleased to welcome uh Dr Mar V Matos uh from salaman in Spain and Dr Tom Martin from UCSF in sou San Franc Isco uh especially grateful to Mary B who was traveling all day yesterday back from San Diego and is joining us today so a special thank you thank you to Mary B and uh Tom a little bit of a shorter flight for you but uh equally thankful f
or you to be uh taking some time after uh being gone for those uh number of days so thank you to to both of you uh next slide yes so yeah just go through those yes so we will have a video replay of the webinar it'll be made available on our website early next week you can find it under the Publications and video tabs additionally it will also be emailed directly to all those who registered for the meeting and at the end of this webinar we're going to have a survey pop up it's a feedback survey w
e really appreciate your um feedback on the program it allows us to build better workshops for you in the future it would be greatly appreciated if you could take a moment to complete that survey all right okay so uh this year was a very active Ash obviously an in-person ash total attendance which uh I'm told was uh most likely a record 32,000 attendees it certainly felt like that that was the case very very busy with over 28,000 uh in person uh and uh uh 4,000 or so uh virtual the total number
of abstracts uh this year uh 7,000 and uh the uh number for Myoma 1,000 uh these slides are uh full screen uh there we go all right yes over 1,000 Myoma abstracts oral 136 plus the late breaking abstract LBA and the plenary abstract and we will be focusing on both of those uh those are considered to be uh the among the best abstracts for the whole meeting so out of the 7,000 uh the LBA and pl plenary are considered to be uh key abstracts presented to a very large audience I think probably in the
range of 5,000 people actually and then uh there were um 850 or so uh posters a lot of different topics are covered this year uh there was some focus on real world data uh we're not going to focus so much on that today uh also uh quite a bit of focus on uh uh equity on access to drugs uh uh these kinds of issues are very very important and we will uh touch on that a little bit at the end uh but for the main part of our discussion today uh we will focus on abstracts that really uh will have a sc
ientific impact immediately and for the Myoma Community overall uh uh for the foreseeable future uh some very very uh important abstracts uh this year uh next slide as always uh we appreciate our sponsors who who support our activities at this specific activity Jansen oncology carform Santa Fe and uh toada thank you so much next slide so um the first two slides focus on what we call Frontline therapy the therapy for newly diagnosed uh multiple Myoma newly diagnosed multiple Myoma and in this cas
e here you can see who are El eligible for Aus stem cell transplantation and this was the results of a trial called the persus trial uh supported by the European Myoma Network emn and this uh particular study was looking at four agents darab bzma belade lenalidomide which is Ravid and dexamethasone uh so Dara vrd versus vrd alone in patients uh with newly diagnosed Myoma next slide and so this shows you uh the the treatment uh protocol and so patients were randomized to either just the three dru
g triplet the VD or with the addition of the darat trumav which is the anti cd38 monoclonal antibody that we have have been using in many different regiments uh these last several years uh patients received four cycles of that the TOA stem cell transplant consolidation with two cycles and moving on uh to maintenance uh with either revid or Duma M plus revid uh making close uh note of the status of minimal residual disease mrd had mrd uh negativity being achieved at 10us 5 or 10us 6 next slide pl
ease and so uh giving uh the immediate uh results that we are seeing so far at approximately four years of followup what we're seeing is that the length of the remission the progression free survival is significantly better with the four drug uh quad combination of Dar vrd 84.3% at 48 months versus 67.7% uh with the vrd at that 4-year uh time Point uh next [Music] slide this correlated with uh an overall increase in the level of complete remission uh either complete remission or stringent comple
te remission uh in which case the um bone Mar plasma cells are negative and the Freel light ratio is normalized uh you can see that complete remission 87.9% versus 78.1% over to the right with all these various arrows you can see that across the board and the different subgroups of patients related to age and race and stage and cytogenetics uh the there was a a shift in favor of the four drugs versus the three drugs next slide now looking specifically at um the achievement of mrd negativity and
this is testing uh of the bone marrow uh to see if any Myoma is left uh looking at sensitivity at uh 10us 5 or 10us 6 you can see uh overall again sign significant benefit uh of the four drug versus the three drug and then double checking at one year at 12 months again sustained mrd negative significantly uh more uh with uh um four drug versus three drug and obviously quite impressive numbers uh over 60% mrd sustained uh in uh in the quad arm so uh uh very impressive really next slide and so ove
rall pretty clear uh that uh the the DAR VD is superior to the vrd uh in terms of the length of the remission the PFS uh in terms of the depth of the response uh CR and mrd negative uh there were no particularly uh unusual um safety signal as one might expect with these regiments which have been used for some time and so uh these data really do support uh the for drug as a potential new standard of care for transplant eligible patients uh next slide just I think we do have obviously it's early d
ays but the overall survival Trend obviously also supports uh the four drug versus three drug uh at this point Point uh next slide so oh yes I guess there's no uh Q&A slide there but so um Mary V uh what what is your take on this obviously um the the fact that um uh the the major benefit was seen looking at um the mrd levels is something that was emphasized by um uh the introduction to this uh the talk by Peter Bor has so so so what is your thinking about uh this study well as you pointed out Br
ian I think that this is excellent because this is the confirmation of the phase two griefing study that your colleagues in the US conducted but here this is a phase three a trial in which the primary end point was progression survival and the primary end point was met and it is a significant benefit in progression free survival I would say for the whole package of treatment including dat Tuma not only as part of the induction but also consolidation after Ono sual transplantation and even as par
t of the maintenance that for two years for me it is very relevant of course the pression for survival the complete respond rate but for me it is very important the minimal residual disase negativity rate because overall it was 75% but the minimal residual disease negative sustained at one year was almost 65% from my this means that many patients will reach two years in minimal residual disease negative and these patients will stop data as maintenance after two years of Maintenance with the data
L will have the opport to continue with the L alone and these patients in case of loss of the complete remission or loss of the minimal residual disease negative can resume again that so in addition of having a new standard of care for our patients with multiple Myoma transplant legible we are introducing something in which we are been we've been working for many years response adaptive therapy and this means that patients maybe don't need to receive lendex plus L plus datas continuous therapy
until progression disase and for me these are the main day home messages of course we have to wait in order to see the benefit in overall survival but this trial definitely something that can change our treatment for patients with newly diagnosed multiple Myoma transplanted volume yeah thank you so much for that what is the reality of potential access to this four drug combo in in Europe what do you expect to happen uh if if this uh is moving forward can this actually be feasible in in uh many c
ountries in Europe what do you foresee being happening yeah I I have to say that in Europe and in majority of the European countries data vrd as induction and consolidation after transplant is a reality right right now because that V was approved but in Europe Len is generic and Len is cheaper than thalidomide and it does not require to do any paperwork so we are already using data VD but only as part of the induction and consolidation so what it is spending is the approval of the maintenance pa
rt and based on the progression for survival based on the minimal resal disease negativity rate based on the possibility of practicing response adapted therapy I think that it would be quite useful for us to get the approval for the whole package wonderful wonderful okay so Tom uh your reaction uh and the impact in in the in the US yeah that um so I completely agree with everything that Mari V said um this is confirmation that the original study that we did the Griffin study uh results were were
validated um basically with Griffin we have been using quad therapy for most people up front but this will change the label on Dar tuab that this will be an approved quadruplet and thus hopefully all insurers will approve this as Frontline therapy um the difference between Griffin and this study for us in the US is Griffin actually stopped the deru at and the lomite at two years people could continue lenol lamide if they wanted this goes until progression but like Mari V said I love the fact th
at they randomize people those that were mrd negative to come off one of the drugs D to me and to continue just lend where the other arm's going to continue um D to M lenide so this will lead I think for us more information on what is the best randomized in randomized fashion what is the best maintenance strategy and for how long you need to do maintenance but honestly for patients Etc this study is going to show that people getting a quad then a transplant and then consolidation and maintenance
with d tab they're going to likely be in remission for seven to eight years from Primary Therapy that's pretty amazing that that's the only treatment they're going to need for the first seven to eight years as they're getting therapy and some people may not relapse exactly exactly this I think it is really uh practice transforming and uh will have a huge impact for patients uh so absolutely um so let's uh go forward and and take a look at the other trial um uh somewhat similar uh this this tria
l uh also from the European myom Network which is really showing its strength at these meetings uh really the ability to do these large randomized phase three trials in this case is a tuab instead of DaRuMa and cilam instead of valky so looking at the four drugs is the tuab corilam lenol and deex versus the three drug corilam lenite andex uh next slide it shows the uh schema somewhat similar but but um uh it it has uh some different elements for Cycles transplant uh for cycles and then what they
call light consolidation so a little a little bit different uh and so uh mrd measured uh post induction and post transplant uh consolidation and the light consolidation next slide and again uh and the numbers are rather similar um uh at the 10 the minus 5 level uh 77% versus 67% 67% versus 48% 10 Theus 6 so again significant uh benefit at the mrd negative level next slide and across the board uh benefit uh and using the NGS uh method uh next slide um and so the the one thing that they did empha
size and this does relate to the use of uh the coril the kyprolis versus the velcade is the impact in the high-risk setting and they did make note of patients with uh two or more high-risk features uh showing a significant benefit with the uh four drug versus the three drug and so I'll be interested in uh Mary ve and Tom's thought thoughts about uh the interpretation of that in in this particular trial uh next slide and so uh conclusions very similar four drugs are better than three drugs uh a t
olerable safety profile uh 10 Theus 6 uh is very informative they did not have data on the one-ear mrd negativity the systemed mrd uh data yet uh they will be having some uh longer followup uh so uh Tom I'll start with you uh next uh so so so so what is your take on this study uh particularly in comparison with the uh uh with the pereus study yeah sure that um both studies I really enjoyed listening to and seeing the results of both studies and I think both studies really form the basis that We
Believe quads are better than triplets this study is a lot less mature than the persus study right so 24 months of follow versus twice as much four years of followup essentially and so therefore we really only have mrd data from initial evaluations we don't have a PFS data I will say in so to go at your point Brian about the high risk in the US some people would choose Dara RV d as initial therapy for non highrisk and would potentially do krd in the highrisk that's what's that's what the practic
e in the US is some some up B mostly because cd38 plus krd has not been approved by most insurance is just because of cost so you choose one versus the other I think these data in my mind show that I probably would choose Dara RVD versus just krd without a cd38 but if I have somebody that has double what we're calling double hit Myoma I would love and to try to use these data to get insurers and nccn guidelines to approve the use of cd38 plus krd as Frontline therapy and the truly the real high-
risk the double the double hit patients so I hope this is going to increase our ability to use cd38 Plus krd in the Frontline setting but I would probably just do that in the patients that had truly real high risk disease right right Mary V your reaction yeah my reaction is also very positive although I completely agree with what Tom said this study is more immature and honestly I would like to have seen a progression fre survival Cur but this was not possible and the minimum residual disease ne
gativity rate is impressive so I think that Francesca had the opportunity in front of a very big audience in front of all members of the American Society of hematology to put in context the value of the minimal residual disease in Myoma and for me this is extremely important and in addition as you pointed out this study has been conducted by the European miloa Network in many European centers and the mrd assessment was centralized but this mean that this is possible so I can consider that this t
rial also from the political point of view is very positive in order to move forward to reach minimal residual disase and Myoma as an important end point and we have to wait but I can imagine that the outcome in the future for these patients or almost 80% of the patients achieving minimal receival dises negative the outcome will be excellent but I have to to say that in contrast with what Tom said for the changing in the practice in the US in Europe it is going to be much more difficult to incor
porate Cari as part of the first line of therapy because you know that until now the phase three clinical trials trying to put Caril in the first line of therapy have not been positive and this is the reason why here in Europe carfield so not approved but it's to that I have just reive an email and the idea is to put together all data from all clinical studies that we have with Cari sub in the first line therapy in combination with the anti 38 monoclonal antibodies in order to go to the authorit
ies in order to see if it is possible to get the approval because it's true that isim in this case KD in patients with high risk p especially in the patients with a double heat two or more High recog gentic AB normalities the mrd negativity rate was 77% and this is what patients with high risk need to reach minimal residual disease negative because this is the parameter able to overcome the poor prognosis so this would be my Teo message and I would say that much more data from the East study wil
l be coming in this in the next congresses yeah absolutely thank you so much for that uh I do agree that um this study as well as the other study really put the value of mrd testing into full Focus uh to the to the broad uh Ash audience and uh right at this time as negotiations are ongoing with the FDA and on the European side with EMA I think it is quite helpful to have this C clear uh value of mrd uh testing uh in the assessment uh broadly demonstrated so I think it was quite important uh to h
ave that happen uh at Ash this year so we're going to move forward uh the next abstracts we are going to be discussing them in a little less uh uh detail so that we can get through the program today uh but the next uh topic is uh the results from uh the Spanish team uh uh Mar V that you know very well um uh particularly with uh Bruno but also Naomi uh um working together with the rest of the Spanish team members next slide uh so we're going to touch on two of the several abstracts that came from
Spain this year from salaman and pona next slide uh so so obviously I I think uh what what is clear uh that um uh the analysis of the jam trials has Illustrated with uh many 1,759 mrd assessments the value of uh sustained mrd negativity just exactly what we've been uh talking about the stability of mrd testing uh the sustained mrd testing is clearly uh a powerful guiding endpoint for us to aim for next slide uh and th this uh outperforms any other kind of testing that you might care to conduct
uh that that really mrd is is something which we need to pay attention to next slide uh but the unmat need is that uh the the mrd testing requires certainly for sustained mrd multiple bone marrow aspirate test and uh so there's tremendous interest and this has been a focus of the assessments by the Spanish teams to look at uh better routine implementation of mrd testing into a routine practice next slide and so uh Bruno presented uh the complementary value of different tests using uh peripheral
blood looking at at plasma uh selfy DNA uh and also serum protein testing so uh What uh Bruno was presenting was the results of a an immunomagnetic uh bead approach which he has applied to concentrate the Myoma cells for blood assessment next slide and so uh this is a t test which has been called blood flow so this is a method which takes a large blood sample concentrates the Myoma and uses the normal Next Generation flow method to assess uh the blood sample and this has provided a valuable mrd
assessment at the cellular level looking for Myoma in the blood and you can see here that if you're mrd negative using this blood flow technique uh that does correlate with a longer remission a longer PFS next slide and uh this shows again uh using uh restricted samples uh uh looking at ngf uh again paired samples uh there's a value in being a double negative versus uh uh uh positive or mixed POS positive next slide uh and so the the next question is how do you balance the use of the cellular te
sting with blood flow with mass spectrometry and the idea is that they are definitely complimentary next slide I'm just going through these quickly so that you can see the data and here looking at the combination of uh mrd testing and the Blood using blood flow and then using mass spectrometry uh obviously being negative with both of those really enhances uh the value of negativity and sustained negativity with patients having significantly longer uh progression pre survival next slide uh so dou
ble negative mrd to detection in the blood uh very positive way forward with blood flow and qip mass spectrometry next slide and so basically illustrating that using blood testing can potentially be a more practical way to move towards bringing uh mrd testing into the clinic and allow us to uh assess our patients in this accurate way but in a more practical way uh for the patients and so uh Mar V uh do you see this as uh the reality as the Practical Way Forward uh I know that the um the blood fl
ow method is not necessarily such an easy method to broadly implement but but certainly does provide that accurate assessment yeah sure I think that this is an interesting way and an interesting space in which we have to enter because we know measurable receival disase and detectable measurable residual disease is and maybe the most important prognostic value Factor we have in my but the main problem is we have to go to the bone marrow and especially now with the quadruplet combinations we have
just evaluated many patients will be in minimal residual disease negative and we've seen how the kinetic is extremely important and the evaluation of the measurable residual disease over time is extremely important and it is not possible to go to the bone marrow every three months or every six months even because this is a pain full technique and because of the logistic resources and so on so I think that this is the reason why we have to investigate on the minimal residual disease in the periph
eral blood and I think that this is the result and in Spain you pointed out we are doing next Generation flow in the peripheral blood and is the next blood of the the the Next Generation the blood flow that this is the term for the Next Generation FL flow in peripheral blood and mass spectrometry what are the differences of course we know that blood flow is going to count plasma cells a plasma cells in the peripheral blood and mass spectometry is going to evaluate or to detect the molecular mass
of the monoclonal component so I think that both are complementary as it was demonstrated in this study and if you see well the predictive positive value for blood flow is extremely high and the negative predictive value for mass spectometry is extremely high so I think that both techniques are very very complementary and from my point of view the first important approach is if we go to the peripheral blood and we see that the blood flow or the mass spectrometry are positive it is not necessary
to go to the bone marrow we have to wait because the bone marrow is going to be positive this is as first step but in the future I think that will allow to monitor the absence of minimal residual disease over time in a very simple way and this will allow to do early intervention as we previously seen in the P study in case of reappearance of the minimal residual disease but now if we do a bone marrow annually is to that we are going to lose the probability of early detecting the relapse in many
patients and with these techniques evaluating the measurable residual disease in the peripheral blood we are going to early detect very early relapses in many basan so this would be my main comment and also just a brief comment to the circulating tumor cells that can be evaluated by flow cytometry in the peripheral bladder and those patients in which the circulating tumor cells for example in a small in Myoma remain stable or they are not detectable we have to know that the progression of survi
val is going to be very long and whilst if the circulating tumor cells do evolve over time we have to be pending because maybe we can complement circulating T more cells with the 22020 model in order to refine and in order to optimize the risk of progression to Myoma so I think that all these techniques in the peripheral lad have to be implemented in the clinical practice in the future because we know that b flow as you said it is required 50 cc of peripheral blood and mass spectometry it does r
equire of the technology in order to do but I think that both technologies will be incorporated in the upcoming years or in the upcoming months at least in the academic centers thank you so much for this B yeah so I think that you did emphasize the one point which uh for the blood flow for the cellular testing the the the positive value in other words the finding of the Myoma cells is very predictive in the case of mass spectrometry having a negative result is obviously very very powerful and in
dicative of a of a good outcome uh so in the one case finding cells is bad having a negative result is good so Tom I think what I'm going to do is Skip forward to the next uh abstract Which F focuses on uh so here is the a picture of the Spanish teams such a busy group of teams Mar ve and so many women working in your teams I love to see that right yes it's wonderful uh next slide so Tom thinking about Mass spectrometry uh this is a study from Chicago uh focused on what is the impact of of mass
spectrometry as part of the phase 3 Atlas trial uh next slide and uh the the study here was was relatively straightforward uh within this trial with with krd uh uh and krd versus lenalidomide uh they looked at uh the impact of measuring uh the Myoma protein level using the very sensitive Malto Mass spectrometry method next slide uh and also had a flow cytometry mrd testing next slide and they were able to show uh and they had results at different time points but for them uh the most predictive w
as the Luke um after cycle 18 and this was associated with Superior progression free survival if the mass spectrometry uh was negative and so this is one study that is showing the independent value of the mass spectrometry next slide and uh this shows you what you can see is rather a similar pattern uh using uh uh Next Generation uh uh mrd testing next slide and then also using uh Next Generation flow next slide and so uh double Ms uh and mrd testing as we've just been talking about is uh doubly
favorable and so really another study illustrating the complimentary use of uh these uh testing techniques and it definitely does seem like it is the way forward uh for the future uh next [Music] slide oh yeah because the next slide is the next presentation so so so Tom uh what was your take uh uh particularly focused on uh the value of the mass spectrometry maybe you could comment a little bit more about how you see Mass spectrometry evolving as an available technique uh in the US and and glob
ally actually yes so um I'll try to put it a little bit into context in that these the studies that we're looking at this are mainly frontlines studies and like with the persus study and the esia study um the studies in which we're having great success in really reducing the Myoma burden the question then becomes is what are the what's the best test or which tests can we combined to get our deepest assessment of where the Myoma burden exists how low is the my burden at the current time obviously
the spep and the assessment of M protein or L Chains It's not a great assessment of Myoma burden or what's less of the minimal residual disease so we have to get a deeper assessment so this Mass Spec allows us to actually um identify a much lower level of protein in the blood so where we would be in a CR from our prior tests we're still going to be able to detect the the um the my uh the myma protein for multiple more multiple additional cycles of therapy and we get to a very low level by mass
spec and it's Mass Spec negative we know that really there's just minimal residual disease left and so that that's a great thing that we can do it through a simple blood test the question then becomes what's what's complementary to that do we have to do a bone marrow then do a bone marrow to look at flow cytometry of the bone marrow to see how many Myoma cells out of a million or still in the bone marrow that's something we could do for sure and those have been shown to be complimentary or can w
e do it with this peripheral blood flow cytometry test um the Spanish group that Nobody Does it Better Than the Spanish group that is for sure and the data from Bruno's lab's amazing but I I'll say that that blood flow actually takes 50 MLS to do so that's 10 vial that's a lot of vials to do so we definitely need to have a even an even better way to do it with a lower volume of blood but that blood flow is probably I would in my my opinion almost as good as a bone marrow biopsy and it certainly
would be be able to um for us decrease the number of bone marrows that we're doing for surveillance like Mari ve said we can do surveillance with the mass spec in this in the peripheral blood flow and just Reserve bone marrow biopsies for very infrequent um measures to confirm if they Rd negative so this is this is for sure the wave of the future it's going to spare a lot of B marrow biopsies thankfully for for for the patience right right and I think it's going to take some time this is somethi
ng that's not going to happen overnight I think that we're looking toward the future where we can have this idea of shifting from born marrow to blood uh but we need confirmation and a variety of different settings uh and the like but uh I think it is very encouraging for everyone all of us including patients obviously that blood testing can be feasible uh to have accurate information to guide uh treatment decisions next slide yeah so uh next slide yeah yeah so just what we've been talking about
further perspective studies are definitely uh needed uh next [Music] slide okay so uh now we're going to focus a little little bit on the studies from Iceland and there was uh quite uh an emphasis on the I stop mm uh study that Iceland screens treats or prevents multiple Myoma multiple abstracts in fact um three of the abstract presentations from Iceland uh were selected as uh uh and the presenters received awards from Ash actually for the president ation so it was actually pretty remarkable th
at the data uh from Iceland uh was highly respected and uh appreciated so I'm going to have a bird's eye view of this Iceland project and some of the main uh aspects that were topics of important topics of discussion at Ash uh this year uh next slide uh so um the important thing to realize that at the present time less than 10% of Myoma cases are diagnosed at an asymptomatic stage and so screening for earlier disease could really shift the needle towards diagnosing Myoma much earlier and so one
of the questions is if you screen for Myoma what is the impact in terms of possible earlier diagnosis and so a lot of interest in that next slide ah this is the uh famous uh uh waterfall in uh Iceland it's I can tell you that it's dramatically cold there and windy you want to get back on your tour bus right away after looking at this waterfall next slide uh okay this shows you uh the study that was conducted uh starting 5 years ago now um the screening test was initiated and over half of the tot
al population of Iceland 54% of people in Iceland agreed uh to have their blood tested to see if they had a monocl protein in the blood to see if they had mgus smoldering or active Myoma and uh 29 patients from the screening actually did have Myoma um and then the rest uh were uh randomized uh if positive to no further followup following standard monitoring guidelines or to a much more intensive Diagnostic and monitoring and treatment uh schedule and so three arms to this randomization uh but wi
th a very very large numbers out of the the screening uh 3543 uh new cases of mgus were identified and randomized into the three arms next slide next slide yeah and so um so this year shows you overall what happened uh with the with the progression to smoldering or other disease entities uh and then focusing on Myoma or things related to Myoma when you're screening um monoclonal proteins are associated uh not just with Myoma but other things which can include stoms and lymphomas and things like
that which you see over on the left here next slide but then um the progression was looking at what happens uh uh if you're looking to assess uh whether someone develops Myoma or not if you're being watched closely or not being watched closely and so they established a landmark to see what happens before or after uh the the the uh landmark and uh I'll just keep going here so we can get to what is the uh bottom line uh if you've been screened uh leads to earlier uh diagnosis of Myoma uh and Relat
ed Disorders next slide but the key point was um if you pick up the Myoma earlier if uh uh you're in the screened population what is the status of the Myoma and this is what uh there was a big discussion about at Ash is that the the stage of the Myoma the occurrence of the crab criteria so you're looking at the purple versus uh the gray uh so that um the purple is in the screen population and so the crab criteria with the purple was much uh less uh in uh the patients were screened uh versus thos
e that were not uh and and the the indication is clearly that the uh the disease is being picked up at a much earlier time point which is an important uh discriminator before we have the outcome in terms of overall survival and uh a benefit from screening next slide so yeah so just I'm sorry just go back again for one slide I'm sorry uh yeah just click forward on that yes click forward forward yeah let's go forward yeah so I think that um screening changes the clinical presentation of Myoma is o
ne of the the big takeaways here next slide I'm just going to go through quickly because the results of this were pretty uh clear here you can see um the psychological uh outcomes uh despite what you might think you can see if you look at the bar graphs on the left anxiety and depression did not go up they actually went down people people came into the clinic and were discussing their test results and they were not anxious or depressed if you look over to the right and fact uh they were satisfie
d in fact increasingly satisfied that they had had good answers and things were proceeding in a good way so that there was not a psychologic harm from the screening process coming out of this Iceland study next slide yeah does not increase uh depression anxiety or like dissatisfaction next slide okay uh screening leads to earlier not overdiagnoses it changes the clinical presentation next uh how does the effect survival relating to see that is it worth it uh it does change the face of Myoma and
so Mar V maybe we can start with you uh quickly what what do you think about this in terms of how uh screening will proceed do you think that that screening will indeed be the way forward well personally I consider that the answer should be yes although is to that we need maybe long or followup in order to see more benefit for me I think that it is very clear and I I like very much screening change the clinical presentation of Myoma and this is what we've been defending in all of our clinical tr
ials conducted in high RIS Ming Myoma in spite of many debates for me the major benefit is the benefit the patients can get if they are early diagnosed and we can't prevent or delay the development of craft criteria and this has been demonstrated in the this project and for me this is valid and extremely important in order to plan should we go to screening to the population but I realized that the decision of moving to screening to the population like in Iceland over 40 years this is I would say
a even political decision in which many stakeholders are involved but from my point of view I think that this project is extremely important and if today we can't say we have to do a screening to all population older than 40 years I think that this is something that maybe we do in few years when this study will report benefiting overall survival for me is extremely important the first sentence you put in your slide less than 10% of my Loma cases are diagnosed as an AS an a symptomatic stage and
I think that this less than 10% should increase to at least 80 or 90% right absolutely absolutely so so Tom I think the key Point really is that we're starting to see the clear value of screening but it's the it's the practicality of this that is excuse me is a is a question yeah I AG the devil will definitely be details on how we recommend this but one thing I want to point out and you pointed out Brian in the beginning is in the population of Iceland 54% of the P people said they would partic
ipate in this research study which is pretty amazing in 5% of those screen had had mlus and so just the just the enthusiasm in the participation is amazing and that's how we make advances in myomas by PTI um you know participating in some of these trials so that we can figure out what is the best strategy in all aspects initial screening you know early treatment treatment for relap stud Etc that's why we had so many benefits in multiple Myoma absolutely absolutely and so um I think there is a lo
t of excitement uh thinking to the Future that this can be a way forward and I know now there is a big emphasis in uh thinking about how could in fact screening be practical and feasible and so there are a number of ideas that relate to that and uh excuse me we'll see how this uh moves forward um next slide yeah we'll skip that one yes okay so we're we're kind of running out of time but uh one of the big aspects at Ash this this year was not just just the focus on the immune therapies like car T
cells bispecifics trip specifics but what are the the corelates of that uh what are the multiomic assessments of patients undergoing these immune therapies what are the cyto profiles uh and what are the patterns that correlate with patients who benefit from uh these types of therapy like C T versus patients who might become resistant uh to car therapy and so a lot of interest and this is just one example from Mount siai in New York of a study looking at cyto profiles uh and other immune paramet
ers that relate uh to outcomes with carti so let's just quickly go through this next slide the determinance of early relapse uh looking at the different patterns next slide you can give me just give me the next slide please yeah okay so this shows um what happens in the peripheral blood uh you can see the car T cells across the top you can see the other cells that are occurring the Dynamics in the peripheral blood the landscape after car t uh infusion looking at T cells myoid cells B cells in ad
dition to the C cells which are the little blip across the top uh extending out over uh 10 uh weeks and Beyond next slide and so uh this group looked at the peripheral blood and looked at the patterns uh of uh uh different uh uh cells the C expansion uh and and uh different things that were occurring in patients who uh were having uh a PFS of greater than 18 months uh versus not and they did establish some uh important differences if we just move forward sorry to go through this a little bit fas
t next slide yeah you can see the clear difference between those who did have 18 months BFS versus those that did not next Slide the key thing is that there were clear uh patterns uh indicating the activated or the stimulatory patterns associated with the uh longer responses where versus the regulatory or amino supressor pattern associated with lesser uh benefits so very very interesting to look at these different patterns next slide uh and what they pointed out is that two endogenous population
s the cdat naive uh and uh the mait group significantly higher in those with the longer PFS of 18 months or more uh and so uh a lot of interest in in this as an example of of uh predictive patterns next slide yeah pretty obvious differences next slide uh yes uh mdsc cells were significantly increased in patients with the shorter uh PFS so patterns associated with shorter patterns associated with longer next slide and there are a lot of details in this study as well as many of the studies that we
re presented at Ash this year looking at single cell analysis looking at all kinds of different elements uh in patients next slide yes so um the expansion of activated car T cells and higher serial Lev levels of cyto kindes uh with T Cell proliferation the il12 cd27 28 uh correlated with longer PFS and uh the uh Bor Mar micro environment uh sell mediated uh cd8 naive uh and made were observed in patients with longer PFS immunosuppressive correlated with the shorter PFS uh next slide yeah so so a
nyway this is an example of looking at these kinds of correlations uh Tom I know that you're particularly interested in uh CTI therapy did you feel like this was a kind of a helpful start to get a handle on uh benefit versus lack of benefit yeah so I think the data that was presented there from from Mount Si um was presented by several other groups at this meeting um and we've actually also um found similar data here at UCSF there are ways for us to try to interrogate why C cells are working we
can interrogate the Myoma cell which I'll talk about in a second but we also can interrogate the um the immune cells that are are in the bone marrow and are in the blood that are trying to help the car te- cells work so when you have a product that's manufactured and when you give it back to a patient that has these activated te- cells te- cells that um have they they call it central memory type or or cd8 naive cells those are cells that actually are better at killing the multiple myom cells and
so if you can expand that population when they're infused into the patient that patient's going to have a better um result and what we've actually seen in some of our experiments is that the longer those cells persist too and you saw that kind of that uh brownish bar the the top yeah yeah the ones that have the Carz the later on are the likely the ones that had the best response we're trying to get the Carz to be more persistent on the other side our our immune system in our body wants to try t
o not have too much of activation and some suppression and the cancer like stimulates um you know this immunosuppressive effects and so mdscs or t- regulatory cells or cyto kindes that tell the tea cells to calm down or rest those are associated with not having such a good response after the car T so these are really important lessons for us as we move forward on how we're going to um manipulate and make ctis cell therapy better in the future and we're going to be able to do that we're going to
be able to uh innovate much better than we have in the past with uh autologus transplant and with other Therapeutics with C cells to try to increase the chance that those te- cells are going to be activated and that we're going to be able to get rid of some of these immunosuppressive uh cells before we do the CT cell which is amazing now I'll just mention one thing about the what we've found at many sessions at Ash about the Myoma cell itself is we found that there are mutations that decrease th
e expression sometimes of the Target on the cell surface you know Baseline there's probably more um there's more mutations that actually decrease the number of receptors of gprc5d on the cell surface than bcma so that might be a more likely uh scenario but there's also mutations in the protein so that when the receptor the antibody binds to that protein it binds to a specific spot and there can be mutations in that binding domain that changes it so the antibody or the CTI doesn't bind as well an
ymore so these are things we're going to have to have better tests for ahead of time to actually be able to select the best therapy for each individual patient and then as you know well Tom how those will change over time and as patients sequence through uh these different therapies uh so uh we just have a moment to have some additional takeaways from Ash Mar ve besides these things that we have talked about was there anything else that struck you from Ash any topic or abstract that you thought
was particularly uh important I I would like to to emphasize especially for patients that has in the US the by specific monoc antibodies teista T Ela are already in the market we've had the opportunity to see real world data it's important to mention that in principle some efficacy data looks a bit inferior in comparison with the clinical trials but it's important to remark that majority of the real world data we've seen well approximately 50 60% of the patients would have not been included in t
he clinical trials because they didn't meet the inclusion criteria because the population treated in the real life were more heavily pre-treated with much extr disease Ral imper and so on so for me it's important this the War data that we have to generate and to know this data and other abstracts focus on the optimization of the body specific monoclonal antibodies this is important for the patients the infection management to try to reduce the hospitalization the possibility of using toab in a p
rophylactic way so I think that all these abct majority of them in the poster format can be very useful in order to manage better our patients with my yeah absolutely many many abstracts that covered these topics which are very very important practical points and and Tom some some uh final thoughts from you yeah I'll just point people to two car T Cell therapies that were presented one um targeting gprc 5D so BMS has a um a new cell therapy that targets gprc 5D um Susan ball presented the abstra
ct um and it included you know over 80 patients um it shows that gprc 5D is actually a great Target response rates were in the 90 plus uh um percent range um with CR rates being you know upwards of 50% um and this worked in patients who had prior bcma exposure which is really important and so patients who get a prior bcma therapeutic can go on to looks like to a gprc 5D ctis Cell Therapy the followup is short but it looks like the PFS is going to be you know more than a year we have to see how t
hat all works out over time as we see more followup but it was a very tolerable car um with you know grade one and two CRS as being the most common side effect as well as cytopenias so that was very exciting and another um bcma targeted car it's called DD bcma has shown very impressive response it's 100% and the really important component in my mind it is they're working now in um together with the company kite Pharmaceuticals right to use kite as a way to manufacture their cells so now it's a u
h the company arel and kite have formed a bond and we're hoping that this will increase the number of Slots of G of excuse me of bcma ctis cells that will have available for patients throughout the US and hopefully not to distant future a great point the manufacturing capability in linking with kite can make this uh quite powerful in terms of access uh to a carte which seems to be uh very effective so uh key Point uh one final word from me I think it was intriguing a very small study using uh Ta
b and highrisk moldering Myoma a very small number of patients treated but uh very ve you can say make a small comment 100% response rate 100% MRG negative a long course of therapy but certainly intriguing to see that yeah sure I think that this this trial is exciting the trial planed 24 months of treatment my first comment is maybe it is not necessary 24 months of treatment after two cycles all patients are in a multi negative and based on the safety profile maybe this can be taken into conside
ration in order to reduce the number of cycles and if this does work for high R mold in Mya this would be excellent I have to to know that some trials are coming with by specific monoclonal antibodies and even with ctis for high RIS Ming Myoma so I think that situation is well is excellent yes yes this was intriguing but two years uh really quite challenging yes so thanks again to our sponsors and um uh so I'd especially like to thank uh Dr Mar V Matas from Salamanca in Spain and Dr Tom Martin f
rom UCSF and San Francisco from taking the time to discuss uh these important abstracts from Ash and the takeaways and hopefully this has been in fortive and useful for our listeners and with that I wish everyone a good day thank you again to the sponsors thank you thank you very [Music] much
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