EULAR 2026 Daily Podcast Day 2b Save
Low dose Blinatumomab: Many Relapse with an Unexpected Surprise
Can We Stop PsA Before it Starts?
Impact of Synovial Biopsy-Driven Therapeutic Stratification in PsA
Transcription
You're listening to a RoomNow podcast coming to you from London in UR twenty twenty six. Enjoy. Hey there. My name is doctor Al Kim. I'm one of the leads for the cellular therapy topics at UR twenty twenty six in London, UK.
And today I want to highlight one abstract which was predictable, but there was a really interesting surprise that was very much unexpected. And so this abstract is oral presentation or OP203 entitled Immune Dimming with Low Dose Blended Tumumab Reverses the Treatment Resistant State in Rheumatoid Arthritis, a very provocative title. So Doctor. Laura Buchi from Erlangen, Germany, presented this abstract. And so the background here is that when we're doing these trials of T cell engagers and CAR T cells in autoimmune diseases, almost all the protocols, actually, the protocols were first developed and used in oncology.
Right? And so basically, we're using oncology high doses, in this case of a T cell engager, blinatumomab. And remember, blinatumomab is the very first T cell engager FDA approved for B cell lymphoma. And it's not the best T cell engager that's out there, no doubt. And an additional reminder, blunetuximab is a T cell engager that binds to both CD3, that's going be your T cell engager, and then the CD19 molecule, which are obviously on B cells.
And when that binds to both, both are brought into close proximity and then the T cell kills the B cell. So Laura Bucci previously published a couple years ago that high dose blinatumomab in treatment resistant rheumatoid arthritis did reduce disease activity but there was some toxicity. There was some cytokine release symptom observed. And again, because we're using oncology dosing, they asked the question whether or not a lower dose of blinatumumab can maintain efficacy but reduce adverse events. So they had 15 participants with treatment resistant rheumatoid arthritis.
Blunetuzumab was given at least in two cycles. And these cycles are not trivial. So, it is a continuous ninety six hour infusion of blinatumomab. This low dose was nine micrograms a day followed by a five day holiday. Now, five of these patients received a second dose at a higher dose, twenty eight micrograms a day, and then one patient even received a third dose also at twenty eight micrograms a day.
Everyone is premedicated by high dose dexamethasone, sixteen milligrams. And again, this is to mitigate the severity of any adverse events. So again, the safety issue was one of the questions they were asking. And indeed there was some cytokine release syndrome but it was only three out of fifteen, all grade one. It's pretty encouraging.
There was no ICANS, no hypogammaglottinemia, something we would expect with this type of T cell engager which is relatively low potency and it's not targeting plasma cells in the bone marrow. So your antibody levels remain pretty stable. Now the pharmacodynamics of data that they had was interesting too. They were able to completely remove B cells from the blood by three months. And in fact they also had five patients that got synovial tissue biopsies post blunetimumab and four out of five had no B cells in the synovial tissue.
We have chatted before about the potential importance of of of deep deep depletion of B cells. I. E. Tissue level of depletion of B cells and this may be being a requirement for this immune reset of B cells. So four out of these five patients that were part of the study and were elected to get synovial tissue biopsies did have no B cells in their synovium.
But everyone that participated in the lymph node aspiration part of it, every single participant had incomplete B cell depletion in the lymph nodes. So this actually is interesting because this opens up the possibility that you may not have durable responses, right? Now, looking at efficacy in terms of clinical responses, the ACR20, fifty and seventy were through the roof, 100% ACR20, 73% ACR50, 53% ACR70. Well, the problem though is that very few patients hit remission using the DaaS twenty eight CRP. Only five out of fifteen hit remission at three months.
What's even more concerning and again, maybe not unpredictable is that at month four, ninety three percent, IE eleven out of the fifteen relapsed, right? And again, you may have been able to say, okay, that's interesting but I would expect that this is a lower dose of a T cell engager that doesn't work very well in the first place. And on top of that, we aren't getting rid of B cells in the lymph nodes despite the fact that we're getting rid of B cells in the synovium, right? Now, this is the surprise here. Remember, this is difficult to treat rheumatoid arthritis or treatment resistant.
And they failed a ton of medicines. And so the physicians at Erlogen didn't have many choices to go back to in terms of getting their flare under control. So, they had to start using medicines they had failed before. Most of the patients had to follow this and the interesting thing is after blinatumumab, the medicine they had failed before was reused and they actually were able to restore responses, IE, if they were on a TNF inhibitor and failed it before getting blinatumumab, After getting blinatumumab and then after relapsing, they responded to TNF inhibitor. They also found this with the JAK inhibitors.
This is a really difficult observation to explain. And it opens up a really interesting question whether or not this is a drug specific effect. This is only applicable to blinety two man, but and I can't imagine that being the case. Or is it more of a class effect in therapies that engage T cells or maybe even NK cells that kill B cells? Is this possible with more potent B cell depleting agents that are monoclonal antibodies like obinutuzumab, right?
I think, again, this opens up a really interesting question about how you can remodel the immune system response to the point that their prior resistance to a therapy actually works. So kind of in summary, right, they have this low dose blinatumomab, which got initial efficacy. People did get better, but not all the way. Almost everyone relapsed but then they had these restored responses to failed therapies. So, you know, the group at Erlakin calls this immune dimming, right?
Because you're not really resetting the immune system. You're just kind of stunning it. But again, how that translates to restoration of responses to previously failed therapies is absolutely wild to me. All right. So thanks for listening.
Hello, everyone. This is Nelly Zeade. I'm reporting from URAL, London for RheumNow. And I'm joined today by Doctor. Uta Kilts from Germany.
And we are here to talk about the SERENA study, which is a poster 51 presented at the Congress yesterday. So, Uta, welcome. Happy to have you here. Thank you. Can you just tell us briefly about the study?
Yeah, sure. So the SERENA study is a non interventional study conducted in 19 different countries, included more than one thousand of patients with psoriasis, skin psoriasis, but also PSA and axSpA. I will report here the skin psoriasis data and the post hoc analysis on prevention of PSA in those patients.
Okay and what were the main findings?
So the main findings, they investigate the results over the period of five years and the main question was the proportion of patients that remained free of PSA in this SO population and the short answer is ninety six percent of the patients remained free of PSA resulting in a very low incidence of new PSA development over five years.
Yeah, that's amazing. So you're saying ninety six point nine percent of psoriasis patients remained PSA free after five years on secuclinimod.
Exactly. Yeah, so how confident are you that this reflects a true disease modifying effect rather than just masking early musculoskeletal symptoms? Yeah, this is a non interventional study so we have several limitations to discuss. However, I'm quite confident because we have other independent data on prevention of PSA in Upsu patients that are treated by biologics. So I think that it's really a true prevention because we have data on this biomechanistical approach but also translational data.
However, because this patient population might not be the typical SOHO patient population, We have some limitation here, as we also can see in the patient characteristic where we have, for example, quite a skewed gender distribution compared to other typical populations.
Yeah, so I see in your study that sex and psoriasis duration emerge as two significant predictors of PSA development. Yeah. However, classic risk factors like nail involvement, BMI and PASI did not. So were you surprised by these findings? Do you think they change our clinical risk stratification?
No,
I don't think so because if we as a rheumatologist think about prevention, we will see another population in our patients. In this non interventional trial, it was able to include so patients that are already on secukinumab and as you know in non interventional trials we did not have a very robust documentation of clinical findings like nail involvement, all these other clinical findings. So I think that's a limitation here and we cannot compare our observational study data to the more prevention study data.
Yeah, so do you think now that dermatologists should consider PSA prevention as an explicit treatment goal when initiating interleukin-thirteen inhibitors in patients with BSO?
Yes, absolutely. I think that is one of the goal. First of all, they should have an effective treatment on the skin psoriasis, but on a long run prevention of PSA is one of the main important goals.
Yeah, this reminds me of a study presented by the Greek team by Kukas et al. OP072. They showed that non TNF biologics, interleukin-twenty three and interleukin-seventeen, were associated with lower odds of developing PSA compared to TNF, and they had a longer follow-up with a median of twelve years. So, does this mechanistic make sense to you? So, the positive response with interleukin inhibitors, but not with TNF?
Yeah, absolutely. So, we have, first of all, we have other data that shows that prevention, the risk reduction in prevention is more pronounced in interleukin twenty three inhibitors, for example, and interleukin seventeen compared to TNF. So that's underpinning the existing evidence. Also when we are looking from a translational perspective on that, the inhibition of the cytokines that appear very early in the disease development process, I think that one of the key features here that gives the rationale really that this is a true prevention.
Yeah, So so it's very exciting that to know that we can now prevent a disease from happening. And I'm sure there will be more data of like biomarkers and indicators about how to select these patients and to identify them early. So, you, Doctor. Kilts, for being with me for this interview, and thank you all for listening.
Hi, guys. This is Aurelie Naj from Scotland, live from London, EULA twenty twenty six, day two. I wanted to talk about something I feel like I talk to you about every year. Every year I talk about synovial biopsies. This year though I'm talking about synovial biopsies in PSA as a way to potentially inform therapeutic decision in people with PSA.
However, I'll say it straight away, it is not an abstract that I think will be life changing for now in terms of PSA, but I wanted to talk about it because it has the potential to make us reflect a little bit of what we want to do with these biopsies now that they're becoming increasingly popular. So it's oral presentation 71. And so obviously with all the work done before with randomised controlled trials in RA, with biopsy and strap and therefore RA and so on, there was a feeling that maybe it wasn't ideal or it wasn't something we could use for prediction of response to treatment in patients, And so the idea of this trial in PSA was to look into whether we could inform terrapatec decision using tissue. And a lot of the times in these really fancy studies, there's a lot of transcriptomic proteomics going on, things that you can't really do in clinical practice. So this one wanted to be a bit more pragmatic, and so what they did is they took biopsies from patients, sinovial tissue in thirty five patients, and then they looked at two different things in the tissue which are actually easy to look at.
One was the Crenn score, which is basically the levels of inflammation, and another one was the expression of CDR17 positive cells, which are myeloid cells in the tissue. And it's a simple marker you look at, not a whole complex thing. And so fifteen patients within this thirty five had a high amount of cells, these specific CD117 positive cells in their biopsy, and then the question was, in that case, first of all, do they respond as well to the drug, and what drug should we give them? And so basically it seemed that those patients that had higher inflammatory cells in the tissue, if they were receiving an IL-seventeen inhibitor or an IL-twenty three inhibitor, they were more likely to respond and to have a dapsa low disease activity or remission at six months than if they were receiving TNF. Also, and that's something that I think we kind of know by now, is that the more inflammation in the first place, the better the response, which means that if do give drugs that have anti inflammatory action, it works better when there is inflammation, which that's pretty straightforward.
But the fact that IL-seventeen or IL-twenty three inhibition was better in people with a specific cell signature within their tissue, which is easy to see histologically, was interesting. Now this being said, it kind of also reflects the fact that in some patients they will respond better to IL-seventeen or IL-twenty three anyways, and whether it's because they have this specific subset of cells, it's really, really hard to tell. The sample size was extremely small, nothing was randomized, and it was a single center study. So before getting really excited about this and biopsying every single patient in clinic, I think we really do need to decide whether or not we want a randomised clinical trial. I personally don't know if I would go ahead because I don't think I believe strictly in biopsy to guide therapeutic decision, but certainly if that could help us identify biomarkers that can be found in the blood, I think it would be something extremely helpful in the future.
I think you should look into rumnow.com, rumnow on Twitter or orallyromo if you want more content about EULA twenty twenty six. See you later!
And today I want to highlight one abstract which was predictable, but there was a really interesting surprise that was very much unexpected. And so this abstract is oral presentation or OP203 entitled Immune Dimming with Low Dose Blended Tumumab Reverses the Treatment Resistant State in Rheumatoid Arthritis, a very provocative title. So Doctor. Laura Buchi from Erlangen, Germany, presented this abstract. And so the background here is that when we're doing these trials of T cell engagers and CAR T cells in autoimmune diseases, almost all the protocols, actually, the protocols were first developed and used in oncology.
Right? And so basically, we're using oncology high doses, in this case of a T cell engager, blinatumomab. And remember, blinatumomab is the very first T cell engager FDA approved for B cell lymphoma. And it's not the best T cell engager that's out there, no doubt. And an additional reminder, blunetuximab is a T cell engager that binds to both CD3, that's going be your T cell engager, and then the CD19 molecule, which are obviously on B cells.
And when that binds to both, both are brought into close proximity and then the T cell kills the B cell. So Laura Bucci previously published a couple years ago that high dose blinatumomab in treatment resistant rheumatoid arthritis did reduce disease activity but there was some toxicity. There was some cytokine release symptom observed. And again, because we're using oncology dosing, they asked the question whether or not a lower dose of blinatumumab can maintain efficacy but reduce adverse events. So they had 15 participants with treatment resistant rheumatoid arthritis.
Blunetuzumab was given at least in two cycles. And these cycles are not trivial. So, it is a continuous ninety six hour infusion of blinatumomab. This low dose was nine micrograms a day followed by a five day holiday. Now, five of these patients received a second dose at a higher dose, twenty eight micrograms a day, and then one patient even received a third dose also at twenty eight micrograms a day.
Everyone is premedicated by high dose dexamethasone, sixteen milligrams. And again, this is to mitigate the severity of any adverse events. So again, the safety issue was one of the questions they were asking. And indeed there was some cytokine release syndrome but it was only three out of fifteen, all grade one. It's pretty encouraging.
There was no ICANS, no hypogammaglottinemia, something we would expect with this type of T cell engager which is relatively low potency and it's not targeting plasma cells in the bone marrow. So your antibody levels remain pretty stable. Now the pharmacodynamics of data that they had was interesting too. They were able to completely remove B cells from the blood by three months. And in fact they also had five patients that got synovial tissue biopsies post blunetimumab and four out of five had no B cells in the synovial tissue.
We have chatted before about the potential importance of of of deep deep depletion of B cells. I. E. Tissue level of depletion of B cells and this may be being a requirement for this immune reset of B cells. So four out of these five patients that were part of the study and were elected to get synovial tissue biopsies did have no B cells in their synovium.
But everyone that participated in the lymph node aspiration part of it, every single participant had incomplete B cell depletion in the lymph nodes. So this actually is interesting because this opens up the possibility that you may not have durable responses, right? Now, looking at efficacy in terms of clinical responses, the ACR20, fifty and seventy were through the roof, 100% ACR20, 73% ACR50, 53% ACR70. Well, the problem though is that very few patients hit remission using the DaaS twenty eight CRP. Only five out of fifteen hit remission at three months.
What's even more concerning and again, maybe not unpredictable is that at month four, ninety three percent, IE eleven out of the fifteen relapsed, right? And again, you may have been able to say, okay, that's interesting but I would expect that this is a lower dose of a T cell engager that doesn't work very well in the first place. And on top of that, we aren't getting rid of B cells in the lymph nodes despite the fact that we're getting rid of B cells in the synovium, right? Now, this is the surprise here. Remember, this is difficult to treat rheumatoid arthritis or treatment resistant.
And they failed a ton of medicines. And so the physicians at Erlogen didn't have many choices to go back to in terms of getting their flare under control. So, they had to start using medicines they had failed before. Most of the patients had to follow this and the interesting thing is after blinatumumab, the medicine they had failed before was reused and they actually were able to restore responses, IE, if they were on a TNF inhibitor and failed it before getting blinatumumab, After getting blinatumumab and then after relapsing, they responded to TNF inhibitor. They also found this with the JAK inhibitors.
This is a really difficult observation to explain. And it opens up a really interesting question whether or not this is a drug specific effect. This is only applicable to blinety two man, but and I can't imagine that being the case. Or is it more of a class effect in therapies that engage T cells or maybe even NK cells that kill B cells? Is this possible with more potent B cell depleting agents that are monoclonal antibodies like obinutuzumab, right?
I think, again, this opens up a really interesting question about how you can remodel the immune system response to the point that their prior resistance to a therapy actually works. So kind of in summary, right, they have this low dose blinatumomab, which got initial efficacy. People did get better, but not all the way. Almost everyone relapsed but then they had these restored responses to failed therapies. So, you know, the group at Erlakin calls this immune dimming, right?
Because you're not really resetting the immune system. You're just kind of stunning it. But again, how that translates to restoration of responses to previously failed therapies is absolutely wild to me. All right. So thanks for listening.
Hello, everyone. This is Nelly Zeade. I'm reporting from URAL, London for RheumNow. And I'm joined today by Doctor. Uta Kilts from Germany.
And we are here to talk about the SERENA study, which is a poster 51 presented at the Congress yesterday. So, Uta, welcome. Happy to have you here. Thank you. Can you just tell us briefly about the study?
Yeah, sure. So the SERENA study is a non interventional study conducted in 19 different countries, included more than one thousand of patients with psoriasis, skin psoriasis, but also PSA and axSpA. I will report here the skin psoriasis data and the post hoc analysis on prevention of PSA in those patients.
Okay and what were the main findings?
So the main findings, they investigate the results over the period of five years and the main question was the proportion of patients that remained free of PSA in this SO population and the short answer is ninety six percent of the patients remained free of PSA resulting in a very low incidence of new PSA development over five years.
Yeah, that's amazing. So you're saying ninety six point nine percent of psoriasis patients remained PSA free after five years on secuclinimod.
Exactly. Yeah, so how confident are you that this reflects a true disease modifying effect rather than just masking early musculoskeletal symptoms? Yeah, this is a non interventional study so we have several limitations to discuss. However, I'm quite confident because we have other independent data on prevention of PSA in Upsu patients that are treated by biologics. So I think that it's really a true prevention because we have data on this biomechanistical approach but also translational data.
However, because this patient population might not be the typical SOHO patient population, We have some limitation here, as we also can see in the patient characteristic where we have, for example, quite a skewed gender distribution compared to other typical populations.
Yeah, so I see in your study that sex and psoriasis duration emerge as two significant predictors of PSA development. Yeah. However, classic risk factors like nail involvement, BMI and PASI did not. So were you surprised by these findings? Do you think they change our clinical risk stratification?
No,
I don't think so because if we as a rheumatologist think about prevention, we will see another population in our patients. In this non interventional trial, it was able to include so patients that are already on secukinumab and as you know in non interventional trials we did not have a very robust documentation of clinical findings like nail involvement, all these other clinical findings. So I think that's a limitation here and we cannot compare our observational study data to the more prevention study data.
Yeah, so do you think now that dermatologists should consider PSA prevention as an explicit treatment goal when initiating interleukin-thirteen inhibitors in patients with BSO?
Yes, absolutely. I think that is one of the goal. First of all, they should have an effective treatment on the skin psoriasis, but on a long run prevention of PSA is one of the main important goals.
Yeah, this reminds me of a study presented by the Greek team by Kukas et al. OP072. They showed that non TNF biologics, interleukin-twenty three and interleukin-seventeen, were associated with lower odds of developing PSA compared to TNF, and they had a longer follow-up with a median of twelve years. So, does this mechanistic make sense to you? So, the positive response with interleukin inhibitors, but not with TNF?
Yeah, absolutely. So, we have, first of all, we have other data that shows that prevention, the risk reduction in prevention is more pronounced in interleukin twenty three inhibitors, for example, and interleukin seventeen compared to TNF. So that's underpinning the existing evidence. Also when we are looking from a translational perspective on that, the inhibition of the cytokines that appear very early in the disease development process, I think that one of the key features here that gives the rationale really that this is a true prevention.
Yeah, So so it's very exciting that to know that we can now prevent a disease from happening. And I'm sure there will be more data of like biomarkers and indicators about how to select these patients and to identify them early. So, you, Doctor. Kilts, for being with me for this interview, and thank you all for listening.
Hi, guys. This is Aurelie Naj from Scotland, live from London, EULA twenty twenty six, day two. I wanted to talk about something I feel like I talk to you about every year. Every year I talk about synovial biopsies. This year though I'm talking about synovial biopsies in PSA as a way to potentially inform therapeutic decision in people with PSA.
However, I'll say it straight away, it is not an abstract that I think will be life changing for now in terms of PSA, but I wanted to talk about it because it has the potential to make us reflect a little bit of what we want to do with these biopsies now that they're becoming increasingly popular. So it's oral presentation 71. And so obviously with all the work done before with randomised controlled trials in RA, with biopsy and strap and therefore RA and so on, there was a feeling that maybe it wasn't ideal or it wasn't something we could use for prediction of response to treatment in patients, And so the idea of this trial in PSA was to look into whether we could inform terrapatec decision using tissue. And a lot of the times in these really fancy studies, there's a lot of transcriptomic proteomics going on, things that you can't really do in clinical practice. So this one wanted to be a bit more pragmatic, and so what they did is they took biopsies from patients, sinovial tissue in thirty five patients, and then they looked at two different things in the tissue which are actually easy to look at.
One was the Crenn score, which is basically the levels of inflammation, and another one was the expression of CDR17 positive cells, which are myeloid cells in the tissue. And it's a simple marker you look at, not a whole complex thing. And so fifteen patients within this thirty five had a high amount of cells, these specific CD117 positive cells in their biopsy, and then the question was, in that case, first of all, do they respond as well to the drug, and what drug should we give them? And so basically it seemed that those patients that had higher inflammatory cells in the tissue, if they were receiving an IL-seventeen inhibitor or an IL-twenty three inhibitor, they were more likely to respond and to have a dapsa low disease activity or remission at six months than if they were receiving TNF. Also, and that's something that I think we kind of know by now, is that the more inflammation in the first place, the better the response, which means that if do give drugs that have anti inflammatory action, it works better when there is inflammation, which that's pretty straightforward.
But the fact that IL-seventeen or IL-twenty three inhibition was better in people with a specific cell signature within their tissue, which is easy to see histologically, was interesting. Now this being said, it kind of also reflects the fact that in some patients they will respond better to IL-seventeen or IL-twenty three anyways, and whether it's because they have this specific subset of cells, it's really, really hard to tell. The sample size was extremely small, nothing was randomized, and it was a single center study. So before getting really excited about this and biopsying every single patient in clinic, I think we really do need to decide whether or not we want a randomised clinical trial. I personally don't know if I would go ahead because I don't think I believe strictly in biopsy to guide therapeutic decision, but certainly if that could help us identify biomarkers that can be found in the blood, I think it would be something extremely helpful in the future.
I think you should look into rumnow.com, rumnow on Twitter or orallyromo if you want more content about EULA twenty twenty six. See you later!
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