Total Health Oncology: Best of Heme 2025 Session 2

[00:00] Alright, ladies and gentlemen, we're going to start our afternoon next session now. I'm happy to welcome Dr. Frederick Heigemeister. Once again, he's going to be talking about diffuse large B-cell lymphoma. So Dr. Heigemeister.

[00:20] And okay. Again, okay. So I had a number of things to choose from about updates, but we talked earlier today about prognostic factors, and I wanna talk.

[00:40] and spend the time on mostly bispecific antibodies because I think that's where we are very significantly going to go. Next slide. So this is the scope of the problem for relapsed lymphoma.

[01:00] large cell lymphoma. There has always been talk about, oh the patient had a light relapse from their large cell lymphoma. So we can just give them our chop again because they got a CR with our chop, right? So that's not true. This is some study that looked at a number of patients, 262 patients, we actually had a poster. Also at ASH, this was at ASH as an oral.

[01:20] I picked this because it was more patients and they came up with better conclusions. The disease-specific survival with R-Chomp only, no transplant was done for these people who relapsed more than two years from their diagnosis. That is considered late relapse.

[01:40] But if you look on the right-hand side, these patients, those patients who relapsed less 2 to 5 years are the blue curve as far as PFS is concerned. That's not good. That's terrible in fact. And that is 2 to 5 years. That's still a problem.

[02:00] really in early relapse, isn't it really? And if it's more than five years, that's the red curve. So about 40% may be cured with second line R-chop therapy. So I'm beginning to think, golly, getting R-chop as second line therapy. It doesn't matter when you relapse, whether you have refractory disease,

[02:20] or you relapse late, quote, unquote, late. Yes, you can get complete remissions. There's no question, the overall response rate in this particular study was 72% and the CR rate was 57% less than you might expect their first time around. But it's okay to give our chop. I don't think you're through with therapy if you give our chop. If you have an attention,

[02:40] achieved response, well, you got to go on with something else. And you know what that is. It's going to be CAR T or something because they're going to have disease that's refractory. Next slide. These are novel agents that have been approved recently by the FDA for treatment of relapsor or refractory large B cell lymphoma. And there's something that you can administer without a problem getting them.

[03:00] However, they are not approved, FDA approved for second line therapy of diffuse large salin filma. They are approved for third or subsequent therapies. Polar BR, the CR rate was only 40%. To keep that in mind, I don't like BR. It was done for transplant-ineligible patients. Tafacetabab lense, same.

[03:20] thing, 40% CR rate over a response a little higher. But look at the, and lung castoxamabetesamine, one of the three that I think had the worst patients in it. There were a lot of patients who were refractory who had high risk features at the time of recurrence of their disease. So I'm not

[03:40] surprised that the CR rate was lower. But look at the progression of free survivals. These are dismal median progression of free survivals. They're less than a year, and with Cell and X-Or, which I'm not even going to talk about, the CR rate was only 10%. And so it's a problem, I think, in accepting these drugs as being

[04:00] what we would consider standard of care or good therapy for patients who have relapsed large cell lymphoma. I don't have a problem administering it to people who are sort of a little more frail and that kind of thing, but I always worry about them. I've got a lot of problems in using these particular medications.

[04:20] patients, especially these are the trials. The real world studies results are even worse because they've got refractory patients in them. Thank you. So one of the things we thought is the BTK inhibitors were not going to be very useful in large cell lymphoma. Well, this is Zannabrutinib, which is a BTK inhibitor.

[04:40] covalent. This is non-covalent, covalent-bound BtK inhibitor, plus linalitamide for refractory or relapse LURTS-B cell lymphoma. And the response was a little bit different. The overall response was higher for ABC, but CR rates were similar for ABC and GCP types.

[05:00] These were patients who were ineligible for an atolic system cell transplant and 42% of whom had refractory disease. So these were higher risk patients. But it's relatively impressive that these two medications given together, which are not chemotherapy, one of the things I'm kind

[05:20] focusing on and trying to focus on for you today as well as the things that we are trying to focus on at MD Anderson. And the median was only two prior treatments, but nonetheless this is a very decent progression-free survival, similar to what you saw before and probably better tolerated than polar VR.

[05:40] So, you know, cartease. The cartease results in general for these three studies demonstrated much better results than we expected to see in those patients who had relapsed disease. These, all three agents are FDA approved for third line treatment.

[06:00] of diffused large B cell lymphoma, not second. They are different in the patient populations. They are different in bridging therapies, but nonetheless, the progression-free survivals look very, very similar, and I would have to say that giving these, you would expect to get kind of the same results.

[06:20] I think cross comparisons are really impossible. More importantly, this is second line randomized cartease versus standard of care for relapsed or refractory large cell lymphoma. And the progression free survival for axi-cell was significantly better than standard of care, and making it better treatment.

[06:40] for these patients who have relapsed for large cell onfoma. Refractory or relapsed patients. In addition, the overall survival was also better despite the fact that 57% of those patients who relapsed after autologous stem cell transplant then got a car.

[07:00] So CAR was better to give before the autologous stem cell transplant rather than after. In the transformed study, the curve at the bottom on the left shows those patients who were considered to have refractory disease compared to standard of care therapy, which was an autologous stem cell transplant.

[07:20] right-hand side, significantly better results for those who had relapsed disease rather than refractory disease, but better than standard of care. So the problem with CAR-T, of course, is that it is, quote, designer therapy in essence with limited access due to cost and resource requirements, and there are high toxicity

[07:40] precludes treatment in patients with comorbidities, although more patients can get CAR T than can get stem cell transplants. Patients with poorly controlled disease may not benefit because they may not be able to wait the two or three weeks it takes to manufacture these, and most patients will relapse despite treatment with CAR T cells.

[08:00] So let's talk about bispecifics. The bispecifics, despite the fact that Cartes had varying kind of patients, the bispecific study is all four that I'm going to show you. I won't show you much about odrenaximab, but the four bispecifics, mesunotuzumab, odrenaximab, and epichoritamab, they all had

[08:20] basically the same kind of patients enrolled. And the way that the studies were conducted were very similar, as I'll show you on this next slide. However, gosing is really very different. And you have to look at them carefully when you look at the package insert or how the drugs are administered when you decide to talk to the patient about how they're going to receive it.

[08:40] these medications. For example, Glofidimab, which is the second one here, you give Obenetuzumab. It is the only one of these that in which you have to give a CD20 antibody, naked CD20 antibody before to mitigate CRS. I'm not sure that the dose is right, but everybody knows you give 1,000 milligrams.

[09:00] so have been a 2,000 milligrams. They chose 1,000 milligrams. It was 2,001 trial, but it's 1,000 milligrams. The red boxes show you when you're going to get your full dose of therapy. And notice that with much soon, atuzumab, whether it is given intravenously or subcutaneous,

[09:20] you achieve your full dose within the first cycle. However, with Glofinumab and Otonextamab, you don't get full dose therapy until your second cycle of therapy has been administered. When you then give at Caridumab, you go back and you receive your full dose. They all require step-up dosing is one of the common things.

[09:40] And then there's this how long do you treat them, which is the green box. I got the purple box a little bit with otronextamab because the dose is actually escalated during maintenance, which is kind of weird. You've already achieved a remission, and now you're getting maintenance at a higher dose. However, the others

[10:00] are all different as well. You actually reduce the dose in maintenance with mesinidosumab, keep the same dose when it's given IV, when it's given subcutaneous, you give the same dose for a year. But lofitimab, it's shorter than a year, it's only 12 doses with a dose every three weeks. And then maintenance.

[10:20] therapy is given to the otenexumab and epikaryotumab until the patient progresses. So these are all different ways that they are administered and the dosing administration, which is important to monitor and watch. These are the results for glofitamab, epikaryotumab, and otenexumab. I'm not including mesinotizumab because it is

[10:40] not one of those that was really being considered for large salinfoema. It is approved for, instead, follicular lymphoma. The reasons for the specific, by specific, antibody features are shown here. The age, there was no upper age or 75. The pathologies are shown here are very similar. Step-up dosing was necessary with all of them.

[11:00] them included patients who had Cartes or ophthaloglycem cell transplant. They almost have no CRS or ICANS of significance. They all evaluated refractory relapse status and they collected end of treatment MRD status, which I like because I think that's going to be something important down the road.

[11:20] They also show significant benefit from that standpoint. The PFS looks very, very similar for glofidumab as well as eproterimab, considering CRs and PRs are almost identical. The PRs are higher, of course, with glofidumab, but it's comparing apples and oranges perhaps.

[11:40] This is what happens after you get a CAR T and then you develop a relapse. Only patients who actually receive a bispecific antibody have a significantly better or longer progression-free survival or survival compared to anti-PD1, other chemotherapists.

[12:00] therapy, linalinamide, or other targeted agents. This is an analysis of adverse features influencing outcomes of bispecific antibodies post-cartee. It depended upon whether the patient had sensitivity to treatment prior that they have a CR or not. The earlier relapsed

[12:20] or refractory disease was worse. Additional therapies between CAR-T and bispecific antibody were also made the patients worse and having a relapse within six months since lymphoduplation before CAR-T or Ben-D-Mustain, which is a dangerous drug to administer to a patient with large cell lymphoma whom you're planning on giving CAR-T to.

[12:40] or apparently, lofitimab or other bispecifics. There's another study also that was reported at ASH that if it was less than 90 days from CAR T to relapse, it's very unfavorable compared to relapse more than 180 days. This is an interesting study that looked just at single agent epigretimab for the first time.

[13:00] patients over the age of 75 with untreated, untreated large B-cell enthema who are anthracycling and eligible. Not only the CR rates, but also the progression, free survival and overall survival are relatively impressive for this drug that is given subcutaneously for these older patients.

[13:20] more interesting about this study is they actually described for the first time for me what anthracilclin-ineligible patients really are. I don't see that in many of the patients that I've reviewed or looked at or thought at. Many of the studies just say they were not eligible for

[13:40] or cyclins, but don't give a description. This does. Let's talk about combination therapy. This is Golfidimab plus RICE for relapse to refractory-defuse large B cell lymphoma that was also presented at ASH. The Golfidimab was administered exactly as you would expect with the Stem

[14:00] up dosing and receiving your full dose of 30 mg on cycle 2 and rice was given just before it. Notice that the impressive rate of overall response of 83.3% on the right-hand side with a CR rate of 66.7%. Remember rice that was

[14:20] administered in a randomized study to R-DAP for patients who are going for transplant in Europe where this overall response rate was 50%. This is significantly better and looks much better than does that particular report. In addition, if they happen to be primary refractory, there are 31%

[14:40] the patients, but number of them were relapsed at study entry. But nonetheless, it didn't matter very much. The patients who were primary refractory, there were only 13 patients, but the CR rate was 53.8%. If they had relapsed, it was in the range of 70%. It doesn't matter how long it was from the relapse.

[15:00] This is a really nice trial and a nice study to be able to consider for those patients who would ultimately maybe go for a stem cell transplant. But it is not FDA-approved as yet for second-line therapy. More impressive was this randomized study of GLOFIT Gemox versus R Gemox.

[15:20] for relapse or fratory LBCL ineligible for stem cell transplant. This is also an important study in that the primary endpoint was not progression-free survival, it was not CR, it was not duration of response, it was overall survival. I don't recall having seen

[15:40] seen a trial, a randomized study, in which overall survival was the primary endpoint. That's impressive. It means you have to have a lot of courage and a lot of strength to be able to decide to make that study have primary overalls.

[16:00] survival endpoint. And they were right. The overall survival was significantly better for patients who received GLOFAT Jamox if they were ineligible for a stem cell transplant. Not only from the standpoint of overall survival, but you can see that it is now, it is going to be FDA-approved.

[16:20] more than likely as second-line therapy in June, 2025, this coming June. This is Glofitimab polytusimab. I like this regimen. This is really pretty good for patients who are older, in fact, and are not going to be able to tolerate chemotherapy because there is no chemotherapy in this regimen.

[16:40] These are for patients who have had at least one prior therapy. And this is there is, you can see that across the board on the left-hand side, lower part of the slide, it didn't matter whether you had diffused large B-cellin from a high grade, transformed follicular, primary or mediastal lorale 2 patients, or prior CAR T.

[17:00] Still, CR rates were very, very impressive. On the right-hand side, that's a waterfall plot, and you're accustomed to seeing responses or tumor response and that kind of thing. But this is end-of-treatment CTDNA log fold change by histology. And you can see that all histologies had dropped in their CTDNA.

[17:20] and progression-free survivals were very similar. Patients who had CRs did better. I'm not showing you that slide. This is a follow-up of Polarix, Polytuzum Abarchip versus Archop, and you can see that with longer follow-up, the progression-free survival still remained significantly in favor of Polaric.

[17:40] And as was discussed at the presentation at ASH, it's really, they already had described that ABC subtypes did better, as opposed to GCP that didn't show curves. But what's more important, I think, in this particular presentation is that fewer subsequent therapies were required for the polar archip.

[18:00] green boxes and the different kinds of therapies they received are shown there in the blue boxes are those who got our chop. And the cumulative index of cause of death, including a number of patients, about 200 who came from those who were treated in China, is shown here. Next slide. It is that all deaths are in

[18:20] included in these curves. But the next shows you the non-Hodgkin lymphoma deaths and then the not non-Hodgkin lymphoma deaths. They're about equal. So you need to start, we need to start looking at overall survival from the tumor as opposed to other causes in not only large cell lymphomas but also follicular lymphoma.

[18:40] and mandal cell lymphomas as well. This is Epcaridin-Man plus R-CHOP as front line therapy for patients with large cell lymphoma and an IPI of 3 or greater. These are considered high risk patients because their IPI is high. Look at that PFS. Look at the CR rates. Look at the overall survival.

[19:00] The two overall survival curves that I'm showing you are for those who happen to have, overall, the whole study, 47 patients, but also the double, hit, and triple hit patient. Is this not our top? This is Epigridumab, our top. Could this be a sub-surgical?

[19:20] solution for our problem about giving dose-adjusted Epochar or more intensive therapy? Could we get the same results in those patients who have dark-cell lymphomas? And then this one, which I just, this one is such a good study, I had to include it. This is GlowFit, and you

[19:40] You know, no polar archip versus archop. This is glofet polar archop versus glofet archop, no polar. Randomized study for untreated high risk diffuse lurch B cell lymphomas. IPIs of various kinds were include GCB and ABC subtype for complete response rate didn't matter.

[20:00] it's nearly a hundred percent. The PFS by study arm didn't matter. You didn't have to give, you didn't have to give polar in order to be able to achieve these results as long as you gave GlowFit. In addition, this pet scan

[20:20] And negativity, this was actually patients who were in metabolic PR or the gray boxes. And with further follow-up and no additional therapy, those patients who were in metabolic PR went into metabolic CR with no further therapy and just watching them.

[20:40] You've always suspected that could happen in some of your patients who had a good response and a PR. It's true when you give glofitumab in addition because you've still got something working. We have fellowship program. I'm obligated to show that particular slide. It's a lymphoma fellow.

[21:00] fellowship program that goes on for a year with an option for two years, our first two years. Fellow is currently going through that rotation. We also have and it includes in patient service as well as learning about Cartes. Thank you very much for your attention.

[21:20] Thank you, Dr. Agammaister, for another wonderful talk and welcoming back Dr. Jane who will be speaking to us now about advances in CLL. Thank you.

[21:40] All right, good morning again. So in the second, this talk, I want to talk about advances in CLL and we'll skip the CAR T advances in CLL because I already covered that. We'll talk about BTK inhibitors and some data with BTK degraders which is coming along in the context of CLL.

[22:00] So just as a brief background, this is a recent review article where we wrote and this figure shows different target therapies which have come along for patients with CLL. We have BTK inhibitors. Now there are four different approved, ibrutne, baccala-brutne, xanubrutne, and pitibrutne. We have one BCL treatment.

[22:20] two antagonists, two Venetoclax approved, but there are a couple of others in phase three studies, namely Sondrotoclax and Lisafteclax. We have CD19-KIT approved. We have PA3-Kines inhibitors approved, but they are not used much these days. And then we also have Obenetuzumab, as well as obviously Rituximab for use for these patients.

[22:40] In the field of CLL, a lot of emphasis has been now these days of combining these therapies to get the maximum benefit out of it and to make them into time and data approaches. Also want to briefly show you that it was just about 10 years ago, now coming up to 11 years ago, that Ibrutni was approved for CLL. So we are one decade in

[23:00] to this target therapy era in the context of CLL. And this is really revolutionized, Ibrutna was the first one, but obviously now we have many other agents how we manage patients and chemotherapy has been completely abandoned in the context of CLL. And these are the agents again listed in terms of approvals. You can see,

[23:20] In 2014, as I mentioned, Ebrutna was approved, but now we have several of these agents approved. And if you look at more recently, in 2023, we had Zano-Brutna approved as well as Pirito-Brutna approved, two BTK inhibitors. In 2024, we had Lysosale approved for CLL. And then 25 and beyond, I guess we are looking at, by specific.

[23:40] clinical trials, novel BCL2 inhibitors, novel BTK inhibitors, BTK degraders, or BTK protacts, and I will cover some of them in this talk. So first I want to talk about firstly about the first line CLL and talk to you about a very important abstract which was presented at the ASH meeting. So,

[24:00] Similarly if you're managing patients in the frontline therapy of CLL, we have options of indefinite therapy. You can use a Bruteinib continuously, a Calab Bruteinib with and without Obanituzumab, you can use Zynobrutinib, and here the intent will be you give these BTK inhibitors continuously daily. Or you can have a time limited approach where the approved in the United States is one year of

[24:20] of when urban intusumab based on the CLR 14 study. Also one year of when a brute neb is approved outside of the US in many countries, but not in the US. But the advance I wanted to share with you is the data presented at ASH, which will come out in Union Journal soon, is one year of when a caliber.

[24:40] root nebb with and without ABNITUS map and again the approval is expected soon but you know maybe in the next few months we'll see. So what is that regimen? Before we go to that regimen I just wanted to show you that there's so many of these covalent and non-covalent BTK inhibitors in development. We have BCL2 inhibitors,

[25:00] multiple of them in development. And a lot of what's happening in the clinical trial space and including the phase three randomized study space is combining them in different fashion to make it a time limited approaches. So a lot of effort is being done combining BTK BCL2, so two oral drugs together, and also in terms of triplets.

[25:20] Why don't we use all our best drugs up front, combine a BTK, BCL2, and CD20 antibody. So in this regard, this abstract was presented in an oral presentation at ASH. This is called the Amplify study presented by Jennifer Brown. So this is a study for younger patients

[25:40] with CLL, where the competitor was chemotherapy, and you can argue about the relevance of chemotherapy in the current era, but that was the control arm was. Probably one of the last trials which has used that as a control for their patients. The two experimental arms were important, obviously. So the one was AV, which is one year.

[26:00] year of Venetoclax plus a Calabrutinib. So you start with a Calabrutinib first. For two months you're just getting a Calabrutinib and then you add Venetoclax and both drugs continue for one year. Or you can have a triplet of AVO which is you also had six months of Abinutosumab. So this trial will really

[26:20] for the first time give us a doublet versus triplet in a kind of a randomized study and obviously comparing it to chemaminotherapy. This is the overall treatment characteristic. So this is a large trial, close to 900 patients were enrolled. A lot of these patients were enrolled actually in Europe and outside of North America.

[26:40] and rest of the characteristics were pretty well balanced. And this is the primary endpoint of the study. So the primary endpoint of the study was progression of peer survival as assessed by the independent interview committee. So the green curve here is the chemotherapy arm, obviously not preferring it as well as we would expect.

[27:00] At the top color, 83% is AVO triplet, and then the AV doublet is closed by at 76%. So both the arms were superior, statistically superior to the chemotherapy arm. And I believe based on this, I would expect that both a Cala Ven one year duration and a Cala Ven period

[27:20] of an open, and also for one year duration, may likely get approved by the, should get approved by the FDA. Now in the context of CLL, if you're managing these patients, one of the very important prognostic marker is IgHV status. If you look at the mutated IgHV, which historically has been shown to be more chemo sensitive, you can see mutated IgHV

[27:40] do very well with all the three kind of regimens, including chemotherapy. But if you look at the unmutative IgHV, you see the separation of the curves. In fact, here, the AV or the triplet arm really seems to be doing very well. The doublet of A plus V is slightly inferior at about 10 times.

[28:00] 70% still, both were superior to chemo immunotherapy. Now one of the things which happened in the study was this occurred in the era of COVID. So unfortunately there were many COVID deaths which were largely in the CD20 antibody arm. So there were 10

[28:20] deaths in the AV arm from COVID, but if you look at the AVO and the FCR-BR, both of which have antibody, the number of deaths were, you know, about 7 to 2 to 8%. So there was quite a few COVID deaths which kind of made the analysis a bit more challenging to see, and they did then remove the COVID deaths.

[28:40] from by censoring them and you can see the curves, all the curves slightly improved further. And these are the MRD rates. Dr. Heimster mentioned in his talk about MRD. Interestingly enough, the highest MRD was seen in the triplet, the AVO. The second highest was seen in chemo.

[29:00] therapy and somewhat surprisingly, the blue bar is the AV, the AV triplet of a Cala Ven. So there is a bit of a surprise that it is not performing as well as we would have thought it would. We thought it would be 50, 60% MRD rate, but that was not the case. But still, the PFS curves look better compared

[29:20] into chemotherapy. And this is the overall survival. Again, because there were more deaths from COVID in the antibody arms, if you look in the left curve, there were, you know, the AV arm is better, but if you look, sensor for COVID, all the three arms are doing better. So this trial, you know, lie, will have, for the first time in the year,

[29:40] US one year time limited approach of two oral drugs namely a acala and when approved hopefully in the next few months and I do think that that would change prescribing pattern right now we talk about vengeful one year or continuous BTK inhibitor therapy but when G can be a bit challenging with infusions and

[30:00] TLS monitoring, but I think the SACALA went for one year. I think maybe it's logistically much easier taking two pills for one year. Now you could add a Benitosumab to that as well. I guess then that's a part which we'll have to kind of clarify for which subgroups. This slide just shows you lots of trials are happening in the field of CLL, and the purpose of this slide is that.

[30:20] this frontline therapy will continue to evolve. And there are, and also important one I want to highlight is that the control arm for all these trials, the new trials, except for maybe one or two, is all non-chemo therapy. So the control arm is now vinitoclax, obinidosumab, or ibrutnab, which makes sense.

[30:40] So I think that, I think the next couple of years, some of these randomized trials will read out. The ones I highlighted in yellow are expected to read out at ASH, but we'll see. And I think they are also very important in the field in terms of knowing further about this doublet combinations. Also onto highlight is that besides,

[31:00] In the eryoclax, there are other drugs coming along, like sunrotoclax, and this was also at the ASH meeting that if you combine sunrotoclax with zonobrutinib, so two oral drugs together, very high rates of MRD were achieved for these patients as well. So again, I mean, I think, you know, at the end of the day, we'll have to do some randomized studies too because all these studies are looking very, very hard.

[31:20] very promising in terms of rates of MRD in terms of the PFS. This is work from our group, which was presented at ASH as well, where we have used plateau broadnip in the frontline setting in a triplet regimen. So this is the only triplet plateau-based regimen currently ongoing. This is an investigator-in-chief trial at MD Anderson.

[31:40] One year of therapy, so time and rate approach. And what we showed here is that these are the very high rates of MRD both in the blood and marrow. And also I want to highlight one point is that we checked MRD by clonosic here by Adaptiv. And so these MRD results by clonosic both in the blood and marrow. And the green bar is clonosic.

[32:00] negative at 10 to the power minus six sensitivity. So these are very high depth of remission patients are achieving, not just at the MRE, 10 to the 10 to the power minus four sensitivity, but also at the minus six sensitivity. Now I wanted to touch base on two different new targets.

[32:20] which have been explored in CLL. And one was already mentioned about the bispecific antibody. But I think the real exciting thing which is coming in the CLL in terms of the new drugs is the BTK degraders. So the two BTK degraders were presented at ASH, one by Neurex and one by Beijin. And they're really

[32:40] So the concept behind these degraders is that instead of inhibiting a BTK protein by binding to a pocket like cysteine 4H1S, these degraders degrade the complete protein itself. They just basically degrade the complete BTK protein irrespective of the mutations or anything which may be present there.

[33:00] These are oral drugs. So the Neurex compound, they had 60 patients enrolled, four prior lines of therapy, all patients practically had received prior covalent beta inhibitors, most patients had received rheumatoid as well. So heavily pre-treated patient population, and interestingly, what these

[33:20] So for the BTK degraders, at least so far, we are not seeing the side effects we associate with BTKs, such as AFib, bleeding, arthrogias. So again, they had one patient of AFib here who had prior AFib in the setting, but we are not really seeing those typical AEs we associate with BTK inhibitors.

[33:40] the most common adverse event was a grade 3 or 4 neutropenia of 20%. And this shows the waterfall plot. Again, the duration of treatment is only four months here, so it's early. But as you can see from the green kind of checkboxes here, most of the patients are still on the drug. They're deriving the drug.

[34:00] benefit. So this is, you know, looks like a promising strategy, an oral drug, majority of the patients are responding. So and Beijing had a very similar abstract. They were presented back to back at the ASH meeting, presented by Megan Thompson. Again, the same concept. Just so happens they also happen to have 60 patients.

[34:20] I also happen to have four prior lines of therapy. So it's kind of very similar characteristics of patients. They also did not show any atrial fibrillation. There were a couple of patients with some hemorrhage, but not any typical BTK side effects.

[34:40] They also showed very high rates of response. You can see 93%. And this is their waterfall swimmers' plot. And again, as you can see from the arrows, most of the patients are still on the drug. Here, the median duration of treatment was about 10, 11 months. So it's a slightly more mature data to say. So both.

[35:00] Both these data sets and there's one from AVVY which is coming along as well. I really think that BKD graders if the data in the next one or two years continues to look the way it is looking, I won't be surprised that these drugs may eventually replace inhibitors in the context of CLL. I think these are pretty impressive data. And by surprise,

[35:20] specific antibodies was mentioned the previous talk. They're also coming in the context of CLL. This is Epcoritamab, small number of patients. They're also showing high rates of remission with MRD negativity, which is great, but the challenge so far has been cytokine release syndrome, which again, they're mitigated by step-up dosing. Again, kind of an example.

[35:40] extrapolating from the lymphoma word to say. So that's another drug class which I think you will see more data coming up in this year meeting. My last conclusion slide, I just want to, and then trust of time, I think in the first line BTK inhibitor therapy, first line CLL, I think that there will be major uptake of a calavanetoclax.

[36:00] in the United States given when it gets approved. I think BTK monotherapy may go away in the frontline setting except for patients with del 17 PIP 53 or older frail patients. These other combinations such as Zanoos and Rotoclax, Pirito, Venetoclax, these are still some years away. Phase III trials are underway.

[36:20] but we'll see how they kind of pan out. And the relapse refractory CLL, I mentioned in my previous talk about data with CAR T plus ibrutinib. I think we have to move them into earlier lines of therapy, especially the BTK degraders, as well as by specific antibodies. And with this, I will conclude right on time. Thank you. Thank you, Dr. Ching. Really appreciate you staying on time. Fantastic.

[36:40] talk. We have time for one quick question and then a break. Any questions from the audience? Something? Don't be shy guys, you've been quite all day. Yes sir, Dr. Hegemeyer.

[37:00] with it, having it experienced with BK grades as well as combinations of doublets and triplets and all that kind of thing. So we're working hand in hand with you guys as far as where you're going. Sure. Yeah, that's great to see. Thank you very much.

[37:20] much.