 Okay, so welcome everyone to this webinar, which we hold in order to replace the previous one which had to be cancelled, and I'm very happy to see that many of you returned to this one. And we will listen to Dr. Maria Victoria Mateos, who will speak about the or given overview of the most important data from the field of multiple myeloma, with special regard to the Ash Conference in San Diego. And well, you take it away Dr. Mateos, and we are looking forward to what you've got to tell us. Okay, thank you and good afternoon everyone. First, so thanks to the myeloma patients in Europe for giving me the opportunity to be here with you today, sharing an overview of recent data and updates from Ash in multiple myeloma, and as Thomas mentioned, Ash meeting took place in San Diego in December. Next slide, you can see here like at last American Society of Matology meeting, so almost 1000 abstracts based on multiple myeloma was submitted to this Congress. In fact, the massive number of oral and postures were based on CAR T cells, many important novel updates. And, well, we had the opportunity to listen a new late breaking abstract in which so we are going to have the opportunity to see how a new standard of care for newly diagnosed on myeloma patients, non-eligible for otological systems of transplantation, will be submitted very soon to be approved by the authorities around the world. Next slide. First I will do just so one introduction about the general concepts and we will discuss later on the novel data we have coming from newly diagnosed to myeloma patients and the last part of the presentation will be focused on relax and refractory myeloma patients before to have some minutes for discussion with you. Next slide. Next slide, general concepts. So myeloma maybe you have heard many times that myeloma remains today as some incurable disease. And I decided to start with this slide that was not basically presented at us, but recently published in Black Council Journal and is an international myeloma working group analysis in which you can see here like approximately 15% of myeloma patients can be potentially cured. Next slide. If we wanted to try to identify the patients potentially curable with multiple myeloma, you can see like the age, the thrombocytes level, the novel agents based induction, the maintenance therapy, but the very important the achievement of complete response after a total of extensive transplantation. In other words, the quality of the response is becoming an important surrogate market predicting progress from free survival, but also overall survival and at the end, long-term survivors. Next slide. Let's move on now to focus on newly diagnosed myeloma patients and the next slide. You can see here the standard approach for the management of a newly diagnosed myeloma patients transplant eligible and transplant eligible. You know that the means usually patients younger than 65 or even younger than 70, even the comorbidities are not present and if the performance status is good and the general approach includes according to the ESMO as well as NCSN guidelines, induction, transplant and maintenance. What about the next slide induction? You have to know that in terms of induction before autologous extensive transplantation, all patients should receive it today a free drug-based combination and during this meeting we had the opportunity to see an update about the Bortezomibylinolidomide and hexamedazone VRD data. So you have to know that this combination will be approved by FDA and also in Europe of maybe very soon. When we evaluated the outcome of this combination VRD in young newly diagnosed myeloma patients, the median progression of the survival is of approximately 50 months with a median overall survival that has not been reached yet in patients younger than 65. But in addition to this study, the Spanish myeloma group evaluated also the role of Bortezomibylinolidomide and hexamedazone in a series of almost 500 newly diagnosed myeloma patients compared in this integrated analysis presented at us meeting with the VTD, Bortezomibylinolidomide and hexamedazone. Next slide briefly, you can see like VRD, Bortezomibylinolidomide and hexamedazone is slightly superior to Bortezomibylinolidomide and hexamedazone. In terms of BGPR rate or better, post-induction as well as post-transplant, most importantly the proportion of patients achieving and detectable minimal residual disease after induction and transplant are also slightly higher in comparison with VTD. But you have also to know that the main advantage of VRD versus VTD is derived from the toxicity profile because of the use of lenolidomide, Bortezomibylinolidomide and hexamedazone induced a very low rate of peripheral neuropathy that, as you probably know, is the main adverse event related to the administration of lenolidomide. So in conclusion, these results are further supported by the use of Bortezomibylinolidomide and hexamedazone as the control arm in many ongoing randomized controlled clinical trials. Next slide. New combinations about induction regimen, RDD is going to be the new standard of care, but during our meeting we had the opportunity to see new combinations that are coming. Next slide. The first one is to replace Bortezomibylinolidomide by carfilzomib and carfilzomib in combination with cyclophosphamide and hexamedazone followed by transplant and consolidation with carfilzomibylinolidomide and cyclophosphamide and hexamedazone was compared with carfilzomibylinolidomide and hexamedazone followed or not by autologous transfer transplantation. The next slide, the main message from this presentation is that after induction, after four cycles of induction, carfilzomib in combination with lenolidomide and hexamedazone is superior to carfilzomibylinolidomide and hexamedazone. In the next slide, when we evaluate the overall response rate, the VGPR rate or better, as well as the minimum residual disease negative rate that you can see in blue, carfilzomibylinolidomide and hexamedazone is always superior to carfilzomibycyclophosphamide and hexamedazone. We have to wait to have a long-term follow-up in order to see the final outcome of these patients because, in fact, in this study, you can see here like a supergroup of patients received KERD transplant following by KERD and a supergroup of patients received just KERD 12 cycles without autologous transfer transplantation and the overall response rate was similar. So we have to wait to know how the outcomes of this patient are and we will have these results in the upcoming Congress. But KERD can be in the future another new standard of care to be used as induction maybe before autologous transfer transplantation. In the next slide, another possible combination that we will have in the future are carfilzomibylinolidomide and hexamedazone plus the monoclonal antibody that I do not have. So this combination has been just evaluated in a small series of patients only 16. But in the next slide, you can see like this combination is safer for the patients and the addition of data to MAP to VRD does not result in any safety signal. And in the next slide, you can see like a preliminary overall response rate as well as complete response rate is promising and as well as the minimum residual disease negative rate that reaches 50% at the end of consolidation. Another combination in the next slide also evaluated in a small series of patients is bortesomibycyclofosomide hexamedazone plus the data to MAP. And again, I would give you the same message. So this combination will be maybe a new standard of care in the future because in the next slide, you can see like from the safety point of view, there are not major concerns. And in the next slide, when we evaluated the efficacy, you can see here like after four induction cycles, the overall response rate is of approximately 80% with a significant proportion of patients achieving VGPR rate or better. In the next slide, you can see preliminary progression for survival and overall survival data, but I am not going to focus. Just one second. Am I on the right slide now, or is this the next one that you that you want that you are talking about this one? I am going to, I am talking about right now in the Kumar slide, hexazomibycyclofosomide hexamedazone. Do you see the slide? Data plus hexazomibycyclofosomide hexamedazone in newly diagnosed myeloma patients phase two study. I am trying to find this. Well, I can say which is the slide number 24. Slide number 24. Here we are. Yes. Yeah. Okay. This is just another example of a new combination that maybe can represent a new standard of care. X-azomib, as you know, is a proteasome inhibitor of oral administration and was in this study combined with the lenalidomide and the hexamedazone in combination with the CD38 monoclonal antibody garatumumab. Only 38 patients. Next slide. You can see here like this combination is effective and in fact, so the best response rate was almost 100%, meaning that almost all patients responded with approximately 20% of them in complete response. You have to know that all these studies I am showing you right now are preliminary studies conducted in small cities of patients, but they can be the rationale for moving towards large phase three randomized trials resulting at the end in new combinations, new standard of care to be used in the upfront setting. Next slide. You can see here again this general approach for the management of myeloma in the transplant candidate newly diagnosed patient induction and we have just reviewed the induction transplant followed by maintenance. What is the role of otologous stencil transplantation after induction with the novel agent spatial combinations? In the next slide, you can see the outcome reported by the Spanish myeloma group in a study conducted more than 10 years ago and why this study is important because patients were included in this study and received in blue as you can see proteasome and phalidomide and hexamedazone more than 10 years ago and we can see here like now approximately 25% of the patients remain alive and free of progression. One out of four patients included in this study receiving VTD remained without progression and when we evaluated the overall survival more than 50% of the patients remain alive after 10 years of follow-up and these results have been confirmed also by the Italian myeloma group and this so show a clear message that I would like to share with you the survival of patients with multiple myeloma is significantly improving. In the next slide, you can see here a meta-analysis presented by Michele Cabo from Bologna in Italy putting together data from patients included in three large European studies. In all these studies, patients received induction with proteasome, phalidomide and hexamedazone and approximately half of the patients received single otologous stencil transplantation and half of the patients received double otologous stencil transplantation. In the next slide, the message is that well tandem otologous stencil transplantation so double otologous stencil transplantation is better than single transplant in the intent to treat patient population in the overall population but what is important to note and this is a clear message to put in practice is that the patients with high risk cytogenetic abnormalities or patients with high risk features benefited the most from double otologous stencil transplantation and this is what physicians in Europe are mostly doing in their clinical practice tandem otologous stencil transplantation for patients with high risk cytogenetic abnormalities. The next slide following the general approach for the treatment of young newly diagnosed myeloma patients what about the maintenance and in the next slide you can see like at ARS meeting a new trial was presented evaluating hexasome with the oral proteasome inhibitor as part of maintenance therapy and compared in this case with placebo. You have to know that hexasome was given in this trial only during two years and this study met its primary endpoint and the use of hexasome resulted into a significant benefit in terms of progression of survival versus placebo and in fact the tolerability of hexasome as maintenance is excellent because the frequency of hematological and non-hematological adverse events were really very low so maybe hexasome can be potentially used as maintenance in the future if this drug is approved by the authorities you have to know that although the study met its primary endpoint it stood out the benefit so it's not very evident and in fact the use of hexasome resulted in a median progression for survival of approximate 27 months versus 21 months for patients in the placebo arm. In which situation we can potentially select hexasome to be used as maintenance versus lenalidomide that as you know is the standard of care to be used as maintenance maybe in patients in which lenalidomide can't be given due to poor tolerance or maybe in patients with high risk cytogenetical normalities in which we know that the role of proteasome inhibitor is important and the next step maybe is to combine hexasome in combination with lenalidomide especially in patients with high risk cytogenetical normalities. The next slide you can see here a summary of what we have heard at our meeting regarding the newly diagnosed myeloma patients transplantal eligible VRDS induction the newest standard of care novel combos KERD and maybe this three drug based combination plus the retinoma transplant and concerning maintenance len as a standard of care lenalidomide and hexasome as the new oral proteasome inhibitor anything new in the next slide you can see here like the CAR T cells that as I previously said many oral presentations were based on CAR T cells and one of these presentation was based on the use of CAR T cells in the upfront setting only 10 patients in a Chinese center with high risk that these 10 patients received a CAR T targeting CD19 and BCMA after otolosis and cell transplantation. In the next slide you can see if we focus on the last column the latest response in the purple you can see how 50 percent of patients achieved a stringent complete response 20 percent complete response 30 percent of VGPR and in fact at the bottom of the slide we can see how 60 percent of patients achieved undetectable minima residual disease this is just something very preliminary but of course very promising and maybe we have to move towards the use of these new immunotherapy strategies like CAR T cells maybe in the upfront setting but in patients with high risk. Next slide let's now briefly to evaluate the latest news presented at Ash meeting but based on the transplant in a eligible patient and well we have right now two new possibilities that were presented and updated at Ash meeting the first one is based on a VMP VMP plus data to MoMAB this combination was presented the one year ago and published in New England Journal of Medicine and in fact VMP plus data to MoMAB you probably know that was approved by both FDA and European Medicine Agency and during this Ash meeting we had the opportunity to see an update in the next slide you can see the design of the action study in which VMP was compared with VMP plus data to MoMAB nine cycles followed by data to MoMAB maintenance signal agent in the next slide baseline characteristics of the patients that I am not going to focus on that in the next slide this is a characteristics again I am not going to focus next slide this slide is important and you can see the progression of free survival updated the median follow-up now is 28 months and you can see like there is a big difference between data VMP versus VMP and in fact so the addition of data to MoMAB to VMP resulted into a significant benefit in terms of progression free survival in the next slide you can see like the progression of the survival benefit that was observed across the different two group of patients and in the next slide you can see like the addition of data to MoMAB to VOTES or even Melfalan and Porenison resulted in an overall response rate of 91 percent this means for your information that almost all elderly newly diagnosed myeloma patients who received data plus VMP respond and are able to achieve at least partial response but what is much more relevant is that approximately half of them 45 percent of them achieved complete response and in the next slide you can see how in addition approximately one third of the patients 27 percent achieved minimal residual disease negative and when we evaluate how the progression free survival is when patients achieve the minimal residual disease negative you can see like there is a big difference and the progression free survival is much more longer in the next slide you can see here the evaluation of a surrogate marker for overall survival if this is progression free survival 2 and in the next slide you can see the progression free survival curve that it is representing the curve that we will see when the overall survival data are mature and you can see here like there is already a significant benefit in terms of progression free survival 2 and the benefit in overall survival will be present but we need longer follow up in the next slide important data safety profile safety profile for the patients I would say the first and when we continue with the data to map a single agent beyond the cycle number nine you can see here like the frequency of grade three four adverse event is really very very low and no more than two or three patients develop the respiratory infections back pain or influenza indicating that the tolerability of data to mapping this case in combination with VMP is very good in the next slide so you can see here again the general slide in which so we are going to evaluate another new combinations that we can potentially use in the elderly population lindex plus a vortex or lindex plus data to mumaba lindex plus data to mumaba has been maybe the most important abstract presented at ash meeting and in fact this was presented in the late break in abstract session so an special session in which so the scientific committee select the six most relevant abstracts presented at the congress in this study the nadidomide and examedason was compared with data to mumaba lenidomide and examedason again in the elderly population in the next slide you can see the baseline demographic and clinical characteristics and i am not going to focus on the baseline characteristics in the next slide patient disposition but i think that it's not relevant for your information but in the next slide treatment exposure is not relevant for you but in the next slide you can see the progression for survival and this is important because of the median follow-up is 28 months and again you can see here like the addition of data to mumaba to lenidomide and examedason resulted into a significant benefit in terms of progression for survival and in fact the control arm you have to know that it was very good because lenidomide and examedason has continued therapy resulted in a median progression for survival over 32 months but when we add data to mumaba the benefit is much more evident in the next slide progression for survival benefit across the different subgroup of patients in the next slide again the overall response rate and the overall response rate the complete response rate and minimum residual disease negative rate are similar to that previously reported for data plus vmp 93% of overall response rate 48% of complete response rate and 24% of minimal residual disease negative rate so these results are very good results and in the next slide you can see how patients who achieved minimal residual disease negative have a significant benefit in terms of progression for survival in the next slide the overall survival for preliminary data but again we can see a trend to see a benefit in terms of overall survival for the three combination for the three drug-based combination data to mumaba lenidomide and examedason in the next slide a safety profile acceptable with no menu-matological or non-ematological adverse events and a safety profile consistent with the safety profile i previously said for data plus vmp in the alzion study in the next slide we can see here again the trial in which the bortezomible lenidomide and examedason was compared with lenidomide and examedason alone and in this situation and in this study in the next slide we are going to focus on the elderly population older than 65 or even older than 75 and this combination can represent also a new standard of care for the elderly population because the median progression for survival is approximately three years and the overall survival is over five years so vrd represents also a potential standard of care for this combination in the next slide i think that you can see here the three new standards of care for newly diagnosed myeloma patients non-aligible for otologous dental transplantation data vmp data lenidomide and examedason and bortezomible lenidomide and examedason fda and european medicine agency have approved only data vmp but the other two regimes will be approved in the upcoming months maybe before the end of this year in the next slide just to mention that other combinations that we can potentially have for this patient population and were presented during our meeting lenidomide and examedason as continuous therapy so maybe you know that this is a concept lenidomide and examedason is usually given to our patients as continuous therapy and the lenidomide is hold on doctor just one just one second is this the slide which says management of multiple myeloma in the non-transplant candidate no next slide no the next slide all right thank you so i was saying that the lenidomide and examedason is usually given to our patients as continuous therapy and lenidomide is usually given at the dose of 25 milligrams 20 days followed by one week rest in combination with the examedason 40 or 20 milligrams weekly over in this study what the italian myeloma group did was to compare this conventional standard of care with lendex induction nine cycles full doses followed by lenidomide single agent at low dose only 10 milligrams without the examedason why this study is very important from the patient point of view because the examedason as continuous therapy can influence the quality of life of the patients and can result into the development of significant hematological and non-hematological adverse events so in the next slide we can see how when we did when we give it to our patients lendex followed by lenidomide as continuous therapy the outcome of the patient is better but why the outcome is better because the toxicity profile is better and the incidence of adverse event is inferior so from the practical point of view maybe all physicians treating elderly patients with myeloma after an induction with a lendex full dose it is possible to eliminate the examedason and to continue with the lenidomide at a reduced dose we are going to have the same benefit in terms of overall response rate complete response rate progression for survival but we are going to significantly improve the tolerability what is relevant for the elderly population in the next slide so why i'm going to show you briefly new combinations xasomibidata tumumab and examedason the oral propeasome inhibitor plus the monoclonal antibody and this combination was evaluated in a specific population and fit and frail patients in the next slide just preliminary results because the number of patients is very small only 20 patients but while this combination was effective and especially was safe with a few patients discontinuing the trial due to toxicity in the next slide another possibility is to combine bortesomibel lenidomide and examedason i previously said that this is going to be a new standard of for this combination plus isatuximab and you have to know isatuximab because it's another cd30h monoclonal antibody like daratumumab but daratumumab is already approved and isatuximab is not yet approved but in the next slide you can see how the addition of this monoclonal antibody isatuximab to RVD is effective in this elderly population with a significant proportion of patients achieving at least vgpr and in fact a significant proportion of patients achieved in fact the minimal residual disease negative so these results are very positive and in the next slide as 2018 and let's go to focus now on relapse and refractory myeloma patients and in the next slide you can see here four cardinal points that all physicians have to consider when we have in front of us a relapse and refractory myeloma patients and we have to evaluate the type of relapse the efficacy of previous therapies the toxicity the further options and of course we have also to include the patients preferences the convenience of administration and why not the cost and in the next slide you can see the esmo guidelines 2017 published a couple of years ago and this is the guidelines that most physicians in europe are following right now in order to rescue our patients with multiple myeloma in the next slide is again the same slide in a different format just to mention something important that you have to know the treatment that given as part of the first line of therapy is clearly to influence the treatment that we are going to select at the moment of relapse and this is becoming something very important we have to try to give always the best the first but the first line of therapy is going to influence the second line of therapy in the next slide you can see how patients treated with the bortesomy the basic combinations in the first line exposed or not to leanally the mind but no progressing under leanally the mind therapy so patients non refractory to leanally the mind at the moment of first relapse these patients are usually rescued by carfil so maybe leanally the mind and the exam medicine that are too mobile and a little mind and the exam medicine and it's true that it is possible also to use xasome level and a little mind and the exam medicine or ill or too sum up leanally the mind and the exam medicine during this as congress in the next slide we had the opportunity to see the update of the combination based on data to map leanally the mind and the exam medicine and at the relaxer it is very important to note that the median progression for survival was 44.5 months this median progression for survival is the longest one reported in the relapse setting in a phase three clinical trial and in the next slide we can see how if we add data to move up to leanally the mind and the exam medicine in the relapse setting the overall response rate is 93% and the complete response rate 57% with 30% of minima residual disease negative in the next slide while the outcome for patients receiving data to move up and next in the first relapse and the outcome is better as well as if the patients achieve the complete response the progression for survival is much more longer and there is a benefit in terms of progression for survival too that I previously said that this is a surrogate market for overall survival in the next slide you can see the benefit of data in combination with lentex for patients with high risk cytogenetic abnormalities and this combination is effective in this population and it can represent an option for patients with high risk feature. In the next slide you can see here the evaluation of sustained minima residual disease this is and maybe you have to know that this is a new response criteria published a couple of years ago by the international myeloma working group sustained minima residual disease negativity means that we evaluated today the minima residual disease is negative and we evaluated the MRD again one year later and if the minima residual disease is negative again we can say that this patient is in sustained minima residual disease negative and when we evaluate how the outcome is for these patients with sustained minima residual disease negative you can see like the progression for survival cure is a flat because 100% of patients remain alive and free of donation and this has been evaluated in the pollux study receiving lenalidomide dexamethasone plus data to the mother. In the next slide we can see another possibility patients treated in the first line of therapy with both testimony based combination and exposed to lenalidomide and progressing under lenalidomide therapy so these patients would be I would say lenalidomide refractory. How are we going to rescue to these patients? In the next slide we are going to see how the combinations that we usually select for this for this population are carfil somiband dexamethasone or data to move up in combination with vortex somiband dexamethasone and we can select one or another based on patients preferences patients characteristics as well as disease characteristics. In the next slide during this meeting I had the opportunity to present the update of the use of data in patients receiving this combination in first relapse and when this patient received the data at first relapse the median progression for survival was 27 months and this efficacy was maintained in spite of prior therapy with either vortex somib or lenalidomide what is important and in the next slide you can see this curve data reading after vortex somib and after lenalidomide and in the next slide similar efficacy results you will select the use of carfil somib and dexamethasone as part of the first relapse. In the next slide you can see the outcome of data of the somib and dexamethasone in patients with high recital genetic abnormalities that it's good and it is possible to use this combination. In the next slide again the evaluation of the sustained the minimal recital disease negativity after data vortex somib and dexamethasone and this is also an excellent surrogate marker for progression of the survival as well as also overall survival. In the next slide so this is you can see in gray different boxer different boxes with new combinations new combinations that are going to be used the more and more in first relapses. During this as congress we had the opportunity to see efficacy and safety results from some of these combinations but you have to know that most of them were phase one two clinical trials so the results are not much yet and we need to have the results of phase three randomized clinical trials. In the next slide this is a BC slide that I am not going to focus on that but in the next slide this is a comparison also about the lennaridoma refractory patients. Let's go to move to the next slide and well this is just to summarize that maybe today for patients refractory to lennaridomaid as I previously said we have to rescue these patients with carfil somib dexamethasone or vortex somib dexamethasone plus datatumumab but in the near future new options are coming and these combinations will be pomalidomide vortex somib and dexamethasone, pomalidomide cyclophosphamide and dexamethasone, pomalidomide hexamethasone datatumumab, pomalidomide hexamethasone plus carfil somib or maybe carfil somib dexamethasone plus datatumumab and what about subsequent relapses so patients in third line and beyond do we have new agents to rescue these patients the answer is yes in the next slide you can see in the bottom how new agents pomdex plus something else monoclonal antibodies and novel agents are going to be evaluated in this specific population in the next slide you can see again isatuximabas monotherapy the cd38 monoclonal antibody similar to datatumumab and in the next slide you can see an important message also from the practical point of view when the monoclonal antibody is combined with dexamethasone the overall response rate and the progression for survival duplicated in comparison with the use of the monoclonal antibody as single agent so in the clinical practice maybe if we decided to use the monoclonal antibody as single agent a good option is to add dexamethasone because we are not going to increase the toxicity and we are going to increase the efficacy in the next slide you can see here melphlufen melphlufen is a novel targeted alkylating peptide you have heard about melphalan but melphlufen is not like melphalan it's a new alkylator with different properties and it is much more selective just for the myeloma cells inducing myeloma directed cytotoxicity avoiding off target effects melphlufen in the next slide was evaluated in a series of heavily protruded myeloma patients all of them refractory to datatumumab and refractory to pomalidomide and in this situation the combination is effective the combination is also safe and there are many clinical trials currently ongoing evaluating the role of melphlufen in different settings of patients with multiple myeloma in the next slide you can see selenexor selenexor is also a novel agent that will be maybe very soon approved by our authorities and was evaluated in combination with dexamethasone in pental refractory myeloma patients so patients that have been previously exposed to all conventional regimes and in the next slide we can see here like this combination is effective in terms of overall response rate progression for survival and overall survival with a good safety profile selenexor has to be all has to be always combined with dexamethasone in order to ameliorate some gastrointestinal toxicity but it is acceptable and I repeated this combination will be approved soon by our authorities and selenexor in the next slide has been also combined with datatumumab and dexamethasone in relapsed and refractory myeloma patients and in the next slide you can see like this combination is effective and this is the message I would like to share with you and selenexor is going to be combined with dexamethasone myeloma and also with datatumumab in the next slide so let's go to focus in the last five minutes of my presentation in the immune therapies immune therapy and you can see here in red passive immunotherapy and especially adoptive therapy and cell therapies or new monoclonal antibodies and during the US meeting in the next slide we had the opportunity to see the preliminary results of a new agent that is AMG420 or 420 is an anti-BCMA bite this monoclonal antibody you can see here in this picture like it's a molecule that it is going to target the plasma cell because the plasma cell in the right part of the slide you can see like a BCMA is expressed on the surface of the plasma cells what is the peculiarity of this specific type of monoclonal antibody that this monoclonal antibody in the pink targets the BCMA expressed on the surface of the plasma cells but this bite this monoclonal antibody bring with him the T lymphocyte and you know that the T lymphocyte is the cells that are going to attack and to destroy and to engulf our myeloma cells so it is not necessary that the T lymphocyte arrives to the bone marrow to destroy the plasma cells because these cells are going to be engaged with the monoclonal antibody so these specific type of monoclonal antibodies are very attractive and in the next slide you can see here like this was a phase one study first in human so this is a dose escalation study in which patients started to receive a very low dose of this monoclonal antibody and the important message is that when we evaluated the overall response rate and the efficacy in patients who received the maximum tolerated dose that was 400 micrograms per day in the next slide we can see like these patients and you can see here in the table they are in complete response partial response complete response minimal this is negative minimal this is negative so very encouraging efficacy results we have to take care about the toxicity from my point of view especially infections because some severe infections were reported but this is something completely new that maybe will be improved for sure and while this new monoclonal antibody is going to be expanded and new clinical priors are going to be activated in many European centers and in the next slide we are going to see the results coming from a CAR-T so in the last in the in the last slide you can see how there were two oral sessions in which all presentations were based on CAR-T cells but I decided to show you this because this is new this is a CAR-T targeting again BCMA expressed on the surface of the plasma cells evaluated in China in an unique institution in 57 patients where these patient populations were relapsing on refractory myeloma patients but you have to know that relapsing on refractory myeloma patients in China and this means that these patients have been previously exposed to bortesomib and lenalidomide but these patients have not been previously exposed to data to mumab because in China data to mumab is very expensive it's cheaper for them to have access to a CAR-T than to data to mumab and this is the rational and this is the reason why in China there are so many CAR-Ts in the next slide you can see the overall response rate for these 57 patients included in this study 88% but 74% achieved the complete response and the minimum residual disease negative was negative in 68% of the patients so these responses this overall response rate and complete response rate were really very relevant and in fact the responses were maintained regardless the dose of these cells infused as well as the BCMA expressed on the expression on the surface of the plasma cells in the next slide you can see the progression for survival so CAR-Ts in myeloma are not curative at least at this moment in which we are including in these studies relapsing on refractory myeloma patients the median progression for survival is 15 months and in the next slide we can see here the same progression for survival curve looking how when the patients achieved minimal residual disease negative the progression for survival was longer of approximately two years in the next slide the overall survival median not reached for these patients and when we focus on patients who achieved minimal residual disease negative so at two years 94% of the patients remain alive so these results are again encouraging but well we have to evaluate the more and more these CAR-Ts not only in heavily perpetuated myeloma patients but maybe at earlier stages of the disease in order to see if this strategy can be a potential curative option for myeloma patients. In the next slide this is the list I previously said two oral sessions for immunotherapists including CAR-T and by specific diesel-engaged monoclonal antibodies but well a long list of abstracts based on CAR-T cells with a clear message promising efficacy and safety results but we need a way to have a longer follow-up and to have more and more data and so I stop here and we have at least seven or eight minutes if you want for discussions or questions thank you very much thank you thank you doctor a lot are there any questions or comments from from the audience please indicate perhaps in the chat box and then I can unmute you or you can also raise your hand by pressing the hand button on your control panel which will then indicate here that you would like to speak if you have any questions or comments well it seems that nobody has any questions or comments so I would like to thank you once again for this for this very comprehensive presentation which will then be also I mean the recording of this webinar will also be shared with the wider community and in case you have any subsequent questions or comments to make then of course you're very welcome to write to us at my Alma patients Europe especially to Anava Yeho or even myself my name is Tamar Gretzky so once again thank you very much for the presentation and thank you very much for attending and with this I will say goodbye for today and talk to you again