 So, I'm going to talk about transplants, I'm going to talk about why, who, when, and how, and both in autologous and a little bit in allo, and I'm going to show just a couple of our own data slides here. So when I first started doing myeloma, Dr. Siegel and I, because we're real close when we started doing myeloma, it was, I hate to admit now it's 27 years ago. The average survival was two and a half years, two and a half years, 27 years ago. We do have a regimen called VAD, if we have any old-timers here, VAD is not Velcade, but it was in chrysanidine adromycin dexamethasone. That was a standard therapy up until the 90s, and it was until really 98 when we started, when the Arkansas group actually first found that the lidomide worked. But we did know before that our mentor, because Dr. Siegel and I both worked in Arkansas, came up with the idea that we could take patients with refractory disease, give them high dose of IV malphalin, not oral malphalin, Dr. Suzanne was talking about for amyloid, the oral malphalin, but IV malphalin at high doses could overcome resistance, and sure enough it could. So they decided to move that into the upfront setting, give patients high dose malphalin, it's not a true transplant. Most of what we talk about is really a rescue operation, because the malphalin is non-discriminatory, it's not current, everything now is targeted therapy, right, or genomic base. Genomic dis-killed, indiscriminately, wipes out the marrow, we have to rescue the patients, we give them back their own, at that time it was bone marrow, now we essentially only use stem cells. So up until the 1990s, no one had a better regimen than plain oral malphalin. This is the first trial, it was published way back in 1996, where they looked at high dose therapy versus conventional therapy, it was a French trial, they found the high dose therapy group did better. So since 1996, this has been considered standard of care for patients with myeloma. Current treatment paradigms, initial therapy, which I'm not going to talk about, someone else is going to talk about, and then consolidation, transplant's really consolidating the initial therapy. With current treatment regimens, essentially everyone responds, there are exceptions, we do this all the time, but essentially everyone responds to initial therapy, we consolidate them with a transplant, and then you may want to give either post transplant therapy or maintenance therapy, different issue, that's for patients who are going to get transplanted. Patients who do not get transplanted get initial therapy and they stay on therapy. Current modality and treatment algorithms for myeloma is you never stop treatment for their entire lives. That's the current approach, besides our center, because we don't believe in maintenance therapy, everywhere else in the world you give initial therapy, you stay on drugs, whatever they mean forever. In one drug set doesn't work, you switch to another drug set, no drug holidays for patients with myeloma. And then when they relapse, somebody else is going to talk about what we can do at relapse. So what do we do? For younger patients, almost all of them get three drug regimens, an immunomodulatory drug, we're kind of out of sequence here, but an immunomodulatory drug, a proteasome inhibitor and the dreaded corticosteroids dexamethasone. So this is the current standard for anyone throughout the world getting a transplant and then they're everywhere, except for our center, which I'm going to talk about briefly, usually puts patients on therapy after transplant. We don't, we want, so the questions arise, should you keep torturing patients before the transplant, give them various regimens to get them in the best response or just transplant them or should you just transplant them with whatever response you get with? And then there's this issue of depth of response. Current goal, the surrogate marker right now, which has not been well documented in prospective randomized trials, is minimal residual disease. This is true for myeloma, it's true for ALL, it's true for CLL, it's true for everything about minimal residual disease. So when you look at the different induction regimens, these are category one by the NCCN, no insurance company in the world will give you any hassle about these regimens because they're approved. No one uses Bortesimid doxorubicin dex, doxorubicin, some in Europe do, but no one in the United States use this. It's usually RD, lenolemide dex, lenolemide Bortesimid dex, or one of the things, although it's a category 2A in the NCCN, is carfilzmid lenolemide dex. But for the most part, something like 60% to 70% of the patients in the US get RVD. There's an increasing use of KRD, even though these two have not been compared directly in a head-to-head competition. When you look at the response rates for these various alphabet soups of drugs, if you look at the blue line, the overall response rates are essentially approaching 100%. The drug regimens, regardless of which one you use, has an excellent response rate. So how do you differentiate between one and the other? Again, someone else is probably going to deal with frontline therapy, but you look at the depth of the response. So VGPR is a 90% improvement in their paraproteins. And the VGPR rates do differ some with the different regimens. And then there's the complete remission rates. And the complete remission rates, this is cyclophosphamide, Bortesimid lenolemide dex, not carfilzmib. The complete response rates of over 40% with RVD. I need to add the KRD line over here, because the complete response rates are up here in the 50% to 60% range with KRD. Without a transplant. So if you have this greater response, why do we need to torture the patients, make them lose their hair, put them in the hospital for two weeks, and go through a transplant? Can we just leave them alone and say, we've really achieved a good thing. They're in complete remission. Why should we bother? Patients don't want to do it. The insurance companies don't want to do it. The insurance companies probably do want to do it, because it's cheaper than doing regular therapy. And we need to figure out, should we bother transplanting these patients? So let's give you the data. I'm going to show you at least three trials. This is an older trial, older being 2014, New England Journal Medicine trial. It's done in Italy. They gave Lenomite decks. And then they randomized the patients to a regimen we never use in the US, which is Lenomite oral malphaline and prednisone, versus tandem transplant. So non-transplant, transplant. Then there was a second randomization to maintenance or no maintenance. So we're trying to answer the question here, should you have a transplant or not? Now one of the criticisms of this study is it doesn't contain a proteasome inhibitor. There's no bortesimib or carfosimib in this regimen. So that's one of the problems with this trial, looking at it retrospectively. Bottom line, I'm not going to bore you with all this, is the group that had the transplant and the maintenance group did best. Second best group of the group that had the transplant without the maintenance. And the NPR, the consolidation group lost. When they looked at overall survival, they was a trend to an improvement with the transplant and the maintenance group. That's the first trial. This is a trial that was presented at last ASH meeting. This is a big trial, it's a US French trial. All they showed so far is the US data. The US trial has not met a cruel yet. So it's 700 in France, 700 in the US. This is just the French part of the trial. There's a little bit difference in the trial design. We have everyone gets three cycles and everyone gets their stem cells collected after three cycles. Both groups do. Because this is really meant to be an early versus late transplant trial. Not transplant versus no transplant. Previous one was transplant versus no transplant. This is early versus late. Everyone gets their stem cells collected. This group gets one transplant. They get consolidation with RVD and then they get little of my maintenance. This group gets their cells collected here. They get another five cycles of RVD and little of my maintenance. So they want to look at RVD versus transplant in this comparison. The difference between the US trial and the French trial, this part's the same. The French think that you can't have more than 12 months of linolemide. The US trial is linolemide till progression. So one's a finite maintenance. The other one is indefinite maintenance. This is the data that was the preliminary data. Shows that the progression free survival at four years was superior with a hazard ratio of 0.69. So the transplant group beat the non-transplant group. Overall, response rates are the same. The very good response rates were better. Second primary malignancies, which I'm going to talk about a little bit, were a hair higher in the group that got the transplant versus those that didn't. But wasn't statistically significant at this point in time. Let's skip that. This is a trial that's presented at ASCO. It's actually quite convoluted. It's a European Dutch trial. Where's our man over there trying to stay awake? It's a European Dutch trial where they gave, actually all the elements you'd want, but they gave them in a different sequence. They gave Melflin prednisone bortesimib versus cyborg D, which Suzanne talked about that they use for amyloid. It also works, they learn from the myeloma experience. They get cyborg D, and then this group gets a transplant, one or two cycles, it was dependent on the institution. They could decide one or two. It's not part of the randomization. Then they get either consolidation or no consolidation. So they get proteasome inhibitor here, proteasome inhibitor here, and then consolidation, they get with or without an immunomository drug. And then they all go on linoleumid maintenance. So they have, again, transplant versus no transplant. Both groups have proteasome inhibitor, both groups have an immunomository drug. This is the breakdown, it's actually not of interest. It's a large study, it's 1200 patients. I still can't quite understand their high-risk definitions here, which are higher than we normally see. What they found was that the group that got the transplant had a superior progression-free survival, superior progression-free survival three years, and this was statistically significant with the hazard ratio of 0.73. Transplant beat the non-transplant group. When they looked at the group that had high-risk side genetics, which is a large proportion of their patients, higher than we normally see, the group that got the transplant did better than the group that didn't do the transplant. So when they looked at a actually multivariate analysis, this is a no-brainer. People that get deeper responses have better outcomes. People with standard-risk side genetics have better outcomes. These are all expected. The group that had the transplant hazard ratio overall was 0.54. So 46% improvement in progression-free survival in the group that had the transplant. So there's actually another trial that I didn't show you that's also kind of a contorted trial. So there's four trials of transplant versus no transplant. All of them show a progression-free survival advantage. The older two trials, the original Italian trial showed you, this is another European trial, actually showing improvement in overall survival of transplant versus no transplant. So if you're not convinced, we have to wait till we see further data on both these trials. These are all preliminary data on the ASS and the ASCO trials. So if one transplant's good, two trans is better. So again, this was pioneered in the Arkansas group and the idea was similar to the philosophy with AML. If you have a patient with AML, you give them induction therapy and you give them four cycles of consolidation. Why? It's already in remission after the first cycle of induction because we know they have residual disease. So if you use that concept in myeloma, we know we don't care of them. Well, we should do more than one transplant, you can kill more disease. So this was pioneered in Arkansas group was not randomized, everyone we saw got two transplants, but there were trials that were done in Europe and France where they looked at one versus two. And when they did the one versus two, they found in the French and the European trials that if you didn't get a complete remission, those were the patients who had the better outcome with the second transplant. So everyone was doing second transplants for a while. If they didn't get a good response and then maintenance therapy got thrown into the mix, made it even more confusing. So there is data on one versus two with modern therapy. The trials I alluded to were started in 1994 and 1996. These were ancient trials in this day and age, this one versus two. So do we have modern trials looking at the same question one versus two? This is the same trial I just showed you, the European trial with the consolidation versus no consolidation. And this was a group that got two transplants, one transplant and the ones that didn't get the transplants and in a non-randomized fashion, the group that got two transplants had a superior outcome in the preliminary data analysis. There is a large US trial that I'm on the steering committee, this I almost certain is going to be presented at ASH this year. Two trials, two transplants followed by maintenance, one transplant consolidation, maintenance, or one transplant alone. We're hopefully going to look at this and come up with the answer whether you need two transplants or not. Can consolidation substitute for a transplant? ASH, look for it. Maintenance therapy, this is the NCCN guidelines. Lenelomide and thalidomide, no one I think even in the US or Europe anymore uses thalidomide mainly because of neuropathy. I'm not sure that thalidomide's an inferior drug. In fact, the data with thalidomide maintenance is actually quite good, except that toxicity is so high. Patients can't stay on it very long because of toxicities. There is category two A, I'm going to show you some data on Bortesmib. It's mainly Dr. Sonnenfeld's data on Bortesmib maintenance. There are other regimens, most of the stuff that was done in Europe, mainly by the Spanish group of Bortesmib, prednisone, Bortesmib thalidomide, interferon has been used in centuries it seems like, steroids have been used, and so forth. But they're actually listed as a two beat. Maybe do we know if the response rate and duration of response from salvage is impacted by having a transplant before or maintenance? So most of salvage transplant data that's out there was reported before people were routinely using maintenance. So I can't answer that. We don't have a whole lot of new data since maintenance became standard and then looked at second transplants. There's not a lot of information on that. In fact, there's only one randomized trial of maintenance versus, I mean of transplant versus standard therapies published by the UK group where they either gave a transplant or Cytoxin, transplant group one. But those patients didn't get maintenance before that with linalidomide, which is what we're using now. So I can't answer that question. So this is thalidomide. Thalidomide actually works very well. When you look at the depth of response, you get to a transplant and you get thalidomide, you get a better response. When you look at the three-year vent-free survival it's superior with thalidomide, and you actually look at the overall survival, they're all statistically significant. Thalidomide works. No one can tolerate it. So this is a trial looking at let's, this is a horrible slide. They looked at whether you got maintenance or no maintenance with, so they got, let's just focus on this group. Melfiland, because I don't wanna talk about regular therapy. Melfiland, and then maintenance or no maintenance. The group that got Melfiland and the maintenance had the superior outcome. The overall survivals were not significant in this trial. I showed you this trial before. This is a group that got two transplants to linalidomide maintenance. This is the group that did the best. When they look at the IFM trial, the IFM, the French group did a maintenance with linalidomide versus no linalidomide after transplant. The linalidomide arm had the superior progression-free survival, no difference in overall survival. The U.S. group did a trial of linalidomide maintenance versus placebo maintenance one. They see a difference in overall survival. So they had a progression-free survival and an overall survival advantage in this trial. So there has been a meta-analysis looking at those three trials. Meta-analysis is just like taking a bunch of numbers thrown together to see what you get. I'm not a big fan of meta-analysis, but what they did in the meta-analysis is when they looked at those three trials I just showed you and put the patients all together, they found the group that had linalidomide, the seven-year overall survival was 62% versus 50% translated in two and a half years longer overall survival when they combined the three trials. And that's what's shown on this slide. If anyone wants to have my slides, I'd be happy to give them. So they took the three trials, they found this difference in seven-year survival, and they found this two and a half-year improvement in overall survival. I would like to point out, and the reason we don't use this is this is an ad hoc, this is a meta-analysis. The other trials were ad hoc analyses, maintenance, only one of the three trials showed by themselves before you combined and crunched the numbers together showed a survival advantage. So our thought, our facility is we don't use maintenance because we can always salvage them with maintenance. So our group is like one of the few in the world who doesn't put patients on maintenance and our group is one of the few in the world who doesn't have patients on continuous therapy for their entire lives. Because they get on average about 30 months of three-year remission duration after their transplant without any treatment. We think we can salvage them with linolemide and therefore we don't do that. When you look at linolemide in the context of melpholin, linolemide in the context of melpholin, not linolemide by itself, you can get second primary malignancies, they can be solid tumors, they can be hematological malignancies. So when you look at linolemide with melpholin, you can see in this one linolemide melpholin, solid tumor incidence is 4.4 at five years, hematological malignancies is 3.9. If you don't have any linolemide, it's the underlying risk is 3.4, 1.4. There's no doubt that when you give linolemide in the context of melpholin, sometime within the maintenance start within two to three months, that there's increase in second malignancies. There's no doubt about it. It's small, but it's there. So this, what about fortesimid? This is actually Dr. Sonnenfeld's study. Again, we're dealing with older regimens here. VAD has been christened adromycin dexamethasone. P is PS341, which is what bortesimid, Velcade eventually was initially called adromycin dexamethasone, transplant, transplant, depending on which country, because this was a German Dutch study. The Germans did two transplants, the Dutch did one, right? So, and then they either got thalidomide or bortesimid. And what Peter showed was the group that had the bortesimid before and bortesimid after had a superior progression-free survival, and there was also an advantage for overall survival if you got bortesimid before and after transplant. And the group that actually did the best were those that had two transplants, and the group that got the bortesimid before, two transplants, bortesimid after, actually helped with the 17p deletions, the high-risk patients, and also the renal insufficiency patients. And if I'm wrong on this, he can correct me when he, and tell me. That's my understanding. Perfect, good. So there's another trial where they actually did, another trial from Europe, it's only been reported in abstract form at ASCO, where they looked at bortesimid versus observation. So the other one's bortesimid versus thalidomide, this is bortesimid versus observation. These are the slides. They found that, yes, bortesimid did provide a longer remission duration, it was six months, and overall survival was not different between the two groups. So this trial did, again, showed bortesimid as a superior PFS, but it was only a six-month improvement. This, again, if you go back, they only got four cycles of bortesimid for consolidation or maintenance, whatever you want to call it. What about exasimid, the oral proteasome inhibitor? This is not transplant data. This is data that Sajikumar showed. They did a IRD regimen exasimid linolydex, and then they went on, they could go on to exasimid maintenance. There was 34 patients in the trial, 21 went on to exasimid, I'm gonna give you data on 21 patients. 21 patients, they looked at that, and what they found is they had upgrade in a group that got the IRD followed by I by 48%, and the survival curves look superior for the group that had the IRD with the exasimid versus those that didn't continue. Still not ready for prime time. It's been studied. The study's completed in exasimid versus observation post-transplant. Data's not available yet. It hasn't read out. So minimal residual disease. I gotta get going on this. So this is Sogrelonial's trial slide. This is our patients with their S-PEP. It's above the water. This is when you look at free light chains, then you can look at their bone marrow, you can look at flow cytometry, and down here at the bottom, you can look at molecular or next-generation sequencing, and we need to keep getting to the bottom, and hopefully we can cure the disease. So this is the importance of minimal residual disease. If you get a CR better, this is progression-free survival. CR did better than the groups that didn't get a CR, and actually, when you even divide out the complete remission, the stringent CR versus CR or near CR, stringent CR's deeper response do even better. This is true for PFS as well as OS. When you look at minimal residual disease, these patients are CRs. There's three different technologies. They are now using 10-color flow cytometric analysis, next-generation sequencing, and there is now criteria for PET CT MRD. And again, whichever technology you use, if you get negative, you do better. By looking at minimal residual disease, flow cytometric analysis gets you to 10 to the minus fifth. As far as detecting cells, next-generation sequencing gets you to 10 to the minus six. And PET CT gives you a radiographic look at the overall body, not one point in time. So what happens when you look at MRD? This is by flow cytometry. If you have no adverse features, you have normal cytogenetics and you're MRD negative, you have a great outcome. If you have adverse cytogenetic features and not MRD negative, you have a dismal outcome. MRD does appear to be a surrogate marker for outcomes for PFS as well as OS. I wanna show you a non-randomized trial. Very impressive data. These are two trials they were done sequentially. They weren't done at the same time. Trial A is carfilism of lend decks. Four cycles, no, they did not get a transplant. They get four more cycles and then they stay on KRD actually for two years and go on lend maintenance. So we have KRD essentially for two years and lend maintenance. This trial done after the first one, KRD a transplant and then KRD and then maintenance. So we have the same basic regimen, one with transplant, one without transplant with KRD. Carfilism of lend decks. What they found were that A, response rates keep improving with subsequent lines of therapy. Four cycles, eight cycles, 12 cycles. By the time you get to 12 cycles, the stringent complete remission is 82% in the group that had the transplant versus 51% in the group that didn't. Looks like the transplant really improved the depth of response significantly. What about, let's not show this, MRD evaluation. So there's two different MRD evaluations here. One is done by flow, one's done by next generation sequencing. The white is NGS, the red is flow. The group that had the KRD in the transplant by flow cytometric analysis, 100% minimal residual disease. The group that didn't have the transplant comparing apples to apples, 51%. When you look at next generation sequencing, 75% MRD negative 24%. With this particular regimen. This is a regimen probably of the future. Also, which one of my colleagues is going to talk about, you're going to throw a DeraTumab into the mix. So MRDs at this point is still not, it's a desired endpoint, but we still haven't looked at, if you're MRD negative, you need to do anything. Very important point. So we got rid of their disease, they're MRD negative, do you leave them alone, you need to keep treating them. We don't know. Trials are being done to look at that. Should you keep pounding patients to get them to MRD negative and use up everything you have, and then you don't have anything left after that, we don't know. This is really, it looks great when I show you the progression free survival and overall survival. We're not really sure what to do with it, do we have prospective trials to actually answer that question. Alginic transplant. High response rates. There's a graph versus myeloma effect. There's absolutely a graph versus myeloma effect. Has a mortality in the 10 to 20% range. Using an autologous transplant, the mortality rate's less than 1%, if you're under 70. The mortality rate with even reduced intensity and is still in the 10 to 15%, although I just reviewed a paper that was 5%. So it is better. There is an age limitation. We think in January, for those in the audience, in January, Medicare's gonna have new guidelines for alginic transplant for myeloma. I'm on the committee, the government's already said yes, we had to come up with a protocol, it's gonna happen, that we're gonna be able to transplant Medicare patients. We can't right now, because of sibling limitation, particularly in the older patients, we now have haploidentical transplants. Haploidentical transplants, almost everyone has a kid, a sibling or a parent. It's something like 80 some percent have one of those options that you could use as a potential donor. Opens up for not only myeloma, but for a lot of other diseases of having donors, using a half match. There is probably, based on older data, a plateau in the 20 to 25% range that we probably are curing with this disease. This is a trial that was done, actually started in 2002. It's an 0102, 2002. It was a tandem transplant versus a auto transplant followed by an ALO transplant. So the group that didn't have a sibling donor had two auto transplants. The group that did had an auto followed by an ALO. Large trial, 430 patients, this group, 190 patients, this group, we didn't see any difference in outcomes. In the US trial, part of the problem was we used an inferior transplant regimen. They just got single dose total body radiation. No one does that anymore. Auto auto for progression free survival is identical. Overall survival was also identical. I just saw a week ago the eight year follow-up data looks exactly the same. Even with a high risk patient? Even with a high risk patient at eight years that's not been published, but at the meeting house a week ago, they showed me the eight year follow-up data. It's identical, the two arms. But, because I want to show you this, patients that had graft versus host disease, when they looked at their outcomes, the group that had chronic graft versus host disease had a lower relapse rate in this trial. It's a trend, because there wasn't statistically, wasn't enough patients. In contrast, the Europeans did almost the same trial. Not identical, almost the same trial. They showed a market difference in the group that had auto ALO. That that auto ALO on won. And it wasn't just a little bit they won hands down. When they looked at the group who is progression free survival at 96 months is 22% versus 12%. When they looked at group who are live, 50% versus 36% at 96 months, that the auto ALO group won. So how do you read the difference? We don't know. No one knows the difference. No one can explain this. I don't know why the difference is. So how do you read the difference? I don't know why there's a difference. Has there been any long-term follow-up in terms of high risk disease in the European trial? No, but I can tell you in the US trial, because I unpublished data, not being presented so it's not embargoed, there was no difference in that trial. The definition of 17P are not very common in myeloma. Part of the reason was that the definition of high risk changed from the time they did that trial to now. So that makes it complicated. And then they presented the same definition. Yeah, there are a few people who don't think so. So I mean when the US trial was done, we didn't know about 17P, just for example. So their definition of high risk was 13 by karyotype and high beta two. Our concept of what's high risk has evolved over time as we learn more. This is our data from Hackensack, 118 patients. This is our overall survival of 118 patients with a six-year follow-up. And our overall survival is approaching 70% in patients who are transplanted as consolidation upfront. And even salvaged patients have about a 40% overall survival at six years. This is actually very impressive data for the whole group. The group that had chronic GVHD had a superior outcome to the group that didn't have chronic GVHD. So our survival curves actually look good and chronic GVHD is actually a horrible thing to have to mess with, but the patients did better if they had chronic GVHD. There is an ongoing US trial for high risk patients. They get flu malvalve, a flu-deribin-malphaline-bortesimib, and then there's maintenance to see if we can prevent relapse with the exasme of the oral prism, here versus placebo. There is 21 patients enrolled. There was a stop put in because we had two unexpected early deaths. It's gonna open up again in the next month. Briefly, I don't have time to do this. CAR T cells. Ed, who's over in the other session, published the first paper on CAR T cells. This is his patient of CAR T cells patient got an auto-transplant, didn't have much of a response auto-transplant, got salvage therapy, really was going nowhere. Disease came back, gave hydrocyclofosamide, then they gave malphaline with CAR T cells to CD-19 and look at that. Patient went into complete remission with a lower dose of malphaline, which some people could say, well, maybe it's because their disease evolved, they have a different clone, maybe the malphaline's gonna work again. It's possible. Not probable, but it really looks like the CAR T cells to CD-19 works. The problem with CAR T cells, CD-19, is myeloma patients are only about 20% of them express CD-19? Less than that. So it's not a really good target. So BCMA is supposedly, and my research team is here, supposedly expressed on all myeloma cells, which is apparently not the case, or at least not high levels of it. This is an abstract by Korkendorfer, who presented it at ASCO, of giving a different target for the CAR T cells using the B cell maturation antigen, and they gave a non-oblative regimen, they gave the CAR T cells different loading doses of phase one trial, and you can see here that they did get some responses. This is without myeloma therapy. That's just immunosuppressive therapy, and they got some complete responses with this regimen. They were not particularly durable. All but one of the patients who responded was relapsed within a year, but they did get responses. So in conclusion, auto-transplant standard care, superior to conventional therapy, send your patients for auto-transplant. Maintenance therapy, the multivari analysis shows an improvement. I'm not sure I believe in the multivari analysis, but most centers are using this even though we do not have that philosophy. Future of the world, it's gonna be KRD and DERA, no debt on it yet. It's ongoing trials. There are two meds with one of my colleagues in the talk about the anti-CD38. Early transplant is superior to late transplant. We should try to get MRD, but no one really knows how to get there or what we do with it once we get there. And allergenic transplants remain investigational, but potentially are curative, and we think we project 20 to 30% of the patients. That's it. Questions? Or do I have time? I missed you, David. The patient which did every early CR, I don't know how early you checked that, but early CR do not benefit less from the auto-transplant than the patient who... So I don't know if that anyone's ever updated that data, and we've got a bunch of people here who maybe helped to answer that question. We used to think the patients who responded fast were the ones that actually relapsed fast too, but I don't know if that's really true anymore. But there was one paper, it's actually from Arkansas, I think, that showed the fast responders actually had a poorer outcome. I don't know if that ever held up in any other trials. What do you think? I mean, part of that was a self-fulfilling philosophy because they were looking at response as post-transplant. So obviously, if you continue to demonstrate a slow response for six months after your transplant, that's six months in which you can't relapse. So you have to do a landmark analysis, which they never did. So part of it is just the statistical trick of looking at it that way. Peter? It has been a meat analysis of four large European trials in the frontline setting compared to some protestant and no protestant. In that analysis, more than 1,800 cases done by Dr. Kavanaugh from Italy. Less than CRB4 transplant is an unfavorable proposal. But the CRB4 transplant is much stronger predicted than CR after transplant for a long term. And that's it in that analysis. Thank you. Other questions? Thank you.