CAR T Topic compilation Save

You're listening to a RheumNow podcast coming to you from London in EULAR 2026. Enjoy. Hi, everyone. Welcome to EULAR 2026. I'm in London.

We're gonna do a little preview of the meeting that starts tomorrow, Wednesday, and, we've been over the program. There's a lot of really exciting stuff. I'll just give you some highlights of things I'm gonna be looking forward to, things that I think are maybe game changing in rheumatology. Two late breakers, actually there's a bunch of late breakers that come to mind. The Be Bold data is going to be presented by Joan Marola on Saturday.

There are other late breakers that also look really, really good. I like the, Jack Spare study, that's, LB005. This is a phase three trial of baricitinib given to people with early PMR. They have less than three weeks. It's a 46 patient study, it's not a big study, but they, either get Bari four milligrams or placebo for sixteen weeks, and then part two, they either continue or they crossover.

The primary endpoint is, glucocorticoid free remission, and Bari is a clear cut winner, and it's not surprising that a JAK inhibitor would work. There's a lot of other data out there about other JAK inhibitors working, in polymyalgamatic, and I think it will be, something we'll see more of in the future. Another really important abstract that's coming up as part of the late breakers is a long awaited study, as a follow-up to oral surveillance, where we found out that JAK inhibitors don't do as well as TNF inhibitors when it comes to cardiovascular outcomes and cancer and infection in high risk individuals. The follow-up to that, another big study, not with tofacitinib but with baricitinib, was a regulatory commitment by Lilly to study baricitinib and its venous thromboembolic risk. So, they set up many years ago these studies called RA Bridge and RA Branch, it's baricitinib versus TNF inhibitors in over, three thousand five hundred patients who have risk factors for, VTE events DVT, PE, so we're talking there age, BMI, are the main risk factors on having had a prior event.

And the bottom line on that study is that it confirmed what we already know. Baricitinib was the first of the JAK inhibitors to be, labeled, and right out of the gate, labeled with a VTE risk and warning, and this study confirms it, but interestingly, again, another high risk population, they were average age around 60, but it did not show, this study did not show that baricitinib compared to a TNF inhibitor was associated with either a risk of, cardiovascular MACE events, cancer events, or, it did show infection, serious infectious events, but did not show an increased risk of, of, opportunistic infection. So, in some ways it argues against the data for the oral surveillance study, but those are two very important studies that I think will be coming up this week as late breakers. There's a lot of data that I'm going to be covering with my colleagues on ILD. The bottom line there is it looks like all the risk factors everyone's saying, suggest, yeah, risk factors for ILD in RA is being male, being older, being seropositive, throw in their smoking, throw in their disease activity, and now you've got the profile.

The question is, who needs to be screened? There are a number of studies here this week that look at that issue, they and all say the same thing, ACR guidelines says you need to have one risk factor, the, ERS UR guidelines from last year say you need to have two risk factors, but the bottom line is that almost all RA patients have one or two of these risk factors. Does that mean you do high risk CT in everyone? Well, that remains to be seen. I like this report, it's gonna be, an oral presentation maybe tomorrow, on, it's called the Sun Star Study, and it is a head to head study of, tocilizumab or abatacid after someone fails a biologic or targeted synthetic, and turns out in this study ninety five, ninety six percent of people were TNF inhibitor failures, and it looked like there was no real difference except for when you do the analysis a new way, a different way, there was an edge for Tocilizumab, but we need to cover that to see where that's gonna go.

Other things, there are a lot of studies that have been recently published that are going to get big airtime at this meeting. The Together PSA study, that's the combination of tirazepatide and the IL-seventeen inhibitor, ixekizumab, that data is going to be presented in full here, the AFFINITY study of, with golimumab, the, what else? There's another one that's out there that's going to be presented, again, but I like this, data on, there's going be follow-up data. There's a lot of CAR T cell therapies and B cell depletion therapies, and everybody's excited about it except for me, because one, we're a long ways off from seeing CAR T cell in the clinic. Two, I'm not seeing studies that are of good controls and are blinded.

I'm seeing, you know, 12 people with Munchausen Syndrome getting CAR T and being cured. I'm making that up, that's a joke. But it looks very good, as you would imagine, in lupus, and, somewhat good in scleroderma, maybe not so good in the synthetase myositis patients, and a big question about what it's going to do in RA. The early report on the what's going to be presented here is a small study showing that not everybody gets better but a few people do, and the question is who are they and why are they getting better? The Neptunus study, in Sjogren's syndrome, there'll be a number of Sjogren's presentations.

Neptunus was presented at ACR, that's, enalumab showing its success, now they have some long term data that they're gonna, look at. They have teletacept in Sjogren's, it's also gonna be presented here, and what else? An anifrolumab study with Sjogren's. And then the, Phonics study was just recently presented, and that's going to be shown here as well, and that seems to look good as far as the data goes. So, this is how you can best follow EULAR, when you're not in London with the few of us who are here.

I think the best way depends on how you like to learn. The Twitter feed's gonna be active, the RheumNow faculty is gonna be out there, they're gonna do, you know, six, seven, 800 tweets, you can follow that. There'll be daily recaps starting Thursday night. We're gonna do a day one, day two recap that will, play Thursday evening, probably 7PM, and then there'll be a day three recap on Friday and a day four, final day recap, on Saturday. The recap is where a few of the faculty and myself get together and say, what was great today, and what do you want everyone to know about?

There'll be great articles that you can follow on your phone and, on the website, and they'll come to you as emails, and the other way to follow is to look at take the quiz at the end of the week. Do the weekly quiz on this Saturday and next Saturday, and you'll learn just by doing 20 or 30 quiz questions about, what the take home message from the meeting was. Anyway, it's gonna be a fun time in London. Hopefully, you'll have fun listening to our coverage. Take care.

Hello. I'm Jonathan Kaye reporting for RheumNow from London on the first day of EULAR twenty twenty six. The meeting got off to an excellent start with many interesting presentations. As expected, there are many presentations at this meeting about CAR T cell therapy for a variety of rheumatologic diseases. Georg Schetzgrup in Erlangen has published their impressive and dramatic results with CD19 CAR T cell treatment for lupus, scleroderma, and idiopathic inflammatory myopathies.

At the plenary session this afternoon, Fredrik Albach of the Department of Rheumatology and Clinical Immunology at Charite in Berlin presented the phase one results of their COMPARE trial, which evaluated mivocabtogene otilucel, a human CD19 CAR T cell treatment, in six patients with ACPA positive treatment refractory active rheumatoid arthritis. Patients received lymphodepletion with cyclophosphamide and fludarabine followed by infusion of the CAR T cells. The primary endpoint was safety, and secondary endpoints were clinical and biologic efficacy and a reduction in ACPA. All patients were followed for at least thirty six weeks, and two were followed for fifty two weeks. There was robust CAR T cell expansion with depletion of CD 19 positive B cells from both peripheral blood, bone marrow, and synovium.

All six patients experienced a rapid decrease in disease activity with a median DAS28 CRP reduction of nearly 50%, and imaging confirmed the reduction in joint inflammation. By thirty six weeks, four of the six had achieved an ACR 70 response. All patients were able to discontinue DMARR therapy with continued control of disease activity. Only one experienced a flare that required a brief period of treatment with corticosteroid. The treatment with CAR T cells was well tolerated.

Cytokine release syndrome was limited to mild to moderate events, and there were no unexpected toxicities or cases of neurologic toxicity. There was a marked reduction in ACPA and rheumatoid factor, but not in antibodies to tetanus, suggesting that there are different mechanisms for the development of autoantibodies and protection from vaccination. These results in rheumatoid arthritis are similar to the early results in lupus and other rheumatologic diseases. However, this phase one study treated only six patients and was open label without a control arm. Phase two is ongoing in which five patients will be treated with CD19 CAR T cells, and five others will be treated with rituximab as a comparator arm.

It is most impressive that CD19 CAR T cell therapy results in deep tissue depletion of B cells and allows for complete discontinuation of DMARD therapy. The prospect of long term drug free disease control may make this treatment attractive to patients with difficult to treat rheumatoid arthritis. However, it requires leukapheresis and generation of the CAR T cells as well as pretreatment lymphodepletion. Availability of off the shelf allogeneic CAR T cells should make this approach to treatment more feasible. I look forward to seeing the results of additional studies of CAR T cell therapy in rheumatoid arthritis and in other diseases.

For more information about this and other studies presented at ULAAR twenty twenty six in London, go to RheumNow dot com. I'm Jonathan Kaye reporting from London. I look forward to seeing you tomorrow. Thanks.

Hey there. My name is Al Kim. I'm at ULAR twenty twenty six in, London, UK, and I want to bring up another topic within the cellular therapy space that I found very interesting. Two different abstracts about how what happens when CAR T cells don't work, right? And then how do you manage their disease recurrence?

So again, there are these two abstracts. The first one is OP 76 or oral presentation 76. It was provided by Doctor. Andreas Vershing, named the management of relapses after autologous nineteen CAR T cell therapy and lupus, scleroderma, and inflammatory myopathies, a case series. And then second one, another oral abstract, OP three thirty three, that was presented by Doctor.

Denay Mona Nuthing entitled The Phenotypic Changes of the Peripheral B Cell Compartment Precede the First Case of Relapsed Lupus After CD19 CAR T Cell Therapy. Okay. So this is two reports coming from Erlogen. Alright? So Erlogen has probably the most patients, at a single center that has treated autoimmune diseases with either CAR T cell, CAR NK cell, or a T cell engager.

And in this case, we're focusing just on CD19 CAR T cells from a CD19, yeah, CD19 CAR T cells that is an autologous source. And so here, from a single product, they have fifty patients that were treated. And out of those 50, pretty remarkably, only six has demonstrated a relapse. And it's not the same across all autoimmune diseases. Here in lupus, they had one out of twenty eight with a relapse.

In scleroderma, they had two out of fourteen with a relapse. And in the inflammatory myopathies, they had three out of eight with a relapse. So the median time to relapse across all these diseases was thirteen months. And what's interesting here is what they did in order to get these people back into complete remission. So for the three patients that had myopathies and relapsed, one of them at nine months, another one at ten months, another one at eighteen months after getting the first CAR T cell therapy.

Two of them got a BCMA CAR T. So remember, CD19 does get one type of antibody producing cell called a plasmablast plus every single cell that is preceding a plasmablast, including the pre and pro B cell in the bone marrow. If you did BCMA, this takes care of some of the plasmablast but also primarily the longer living antibody producing cells called plasma cells that are living in the bone marrow. And you can start thinking already the differences that you would have in terms of why you would want to do one or another. If you are targeting CD19, you're making an argument that the pathogenic autoantibodies are coming from plasmodoblast or that there are pathogenic B cells that aren't making antibodies.

And lupus is the best example of this. And again, this Erlogen experience highlights that, that only one out of twenty eight relapsed with a CV19 approach. But if you think that your autoantibody that's pathogenic is coming from a plasma cell, you have to use a BCMA approach, right? And again, with inflammatory myopathies, two out of the three received a BCMA CAR T cell and then one of them had a sustained drug free remission. The second one actually initially started on tofacitinib before getting the BCMA CAR T, relapsed after three months of TOFA therapy, got the BCMA CAR T and it's too early, unfortunately, to report whether or not they went into remission based off of the abstract submission.

The third one actually got a completely different regimen. It got this participant got obinutuzumab plus natezumab, which is going to be your anti fibrotic. And this person actually interestingly improved. The lupus patient relapsed at nine months after getting CAR T cells and then got BCMA CAR T and significantly improved with exception of a mild rash. That was treated with anifrolimab and then the patient went into remission after that.

The two patients with scleroderma, one of them relapsed sixteen months, the other one twenty four months after getting their CAR T cells. Both of them got BCMA, T cell engagers, and they both improved. So I think what this is telling us is that you could potentially rescue these people by using a BCMA approach because whatever is creating the pathogenicity of their autoimmune disease is coming apparently from this bone marrow compartment. So, using BCMA may be the best choice for this. Now, you can argue, why not just target BCMA right after that or even a CD19 and BCMA dual targeting either CAR T cell or T cell engager.

I will tell you the toxicities are not trivial with BCMA across the board. You will one hundred percent have hypogammaglobinemia and a higher rate of infections. I guarantee you that, Right? Is this something that your patient will want to sign off on when the majority alright? We're talking nearly ninety percent of patients treated across the spectrum, at least in the Erlogen experience across different diseases, responded to just CD19 where you don't have to worry about hypogammaglobulinemia or those infections, right?

So it's an interesting question. So the second abstract presented by Doctor. Nuthin was a case report of one of these lupus patients in a different study. There were eleven patients with lupus that received CD19 CAR T cells. One of them relapsed at day two twenty six clinically after getting CD19 CAR T cells.

Now, interestingly in this particular person, several days before, she actually had a routine per protocol collection of her blood and they did immunologic analysis of that pre clinical flare blood sample. They actually found pathogenic B cells, memory B cells, atypical memory B cells in that patient before the clinical flare. So here what you are showing is that there are pieces of information that suggest immunologic flare that then actually preceded the clinical flare here, right? So this actually opens up a really interesting and important opportunity for patients that want to think about CAR T cells or T cell engagers is that there may be a way through labs to predict and detect pathogenic B cells or even rises in autoantibody levels that then end up having, you know, allow you to anticipate clinical relapse, alright? So, you know, again, this is a we've been waiting for these type of data to show up because I think there's been so much discussion about how CAR T cells in particular is kind of a one and done therapy.

It is not. For the majority, maybe, right? But there's an important minority of patients that are relapsing. And it looks like there are ways to be able to get around that. But more importantly, I think there are ways to potentially think about how we can screen in this particular setting using immunologic assays to predict whether or not someone will relapse clinically, and then you can get ahead of the game.

Thanks.

Hello, everyone. My name is Youssef. I am associate professor and consultant rheumatologist in Leeds. I'm reporting for RheumNow at twenty twenty six EULA Congress in London, United Kingdom. Today, I would like to discuss an an abstract titled o p zero seven six.

So this abstract is about reporting the frequency of relapses after CAR T cell therapy in autoimmunity and also how to manage these relapses. As we all maybe already be aware, that back in 2021, the first patient with SLE was treated with autologous CD19 CAR T, and the result was presented the year after that the patient was in drug free remission. So our we we are optimistic about the study initially that this may be a really dramatic changing in the treatment paradigm for lupus. Fast forward five years onwards, we now noted some report, some small cases that patient had relapsed, particularly patient with inflammatory myopathies. So in this study, there were fifty patients that were treated originally at Erlangen using autologous CD19 CAR T cell.

Majority of them were patients with systemic lupus erythematosus, second, followed by systemic sclerosis, and also autoimmune myopathies. So in this longer term data up to over four years follow-up, they reported the frequency of relapses about six out of fifty patients, so amounted to twelve percent. And relapses were mostly mostly, from from the the patient with autoimmune, myositis, particularly with antisynthetase, three of them, two patients, with systemic sclerosis relapse and also, one patient with lupus relapse. And when we're talking about these relapses, they were they were not minor relapse. They were a significant, you know, for example, the patient with lupus had new onset transist myelitis and also cutaneous lupus whereas some other patients with anti sigmoid syndrome had a relapse of myositis and also interstitial lung disease.

So these are really in severe relapses. And what they did in this cohort were that they were treated predominantly with the BCMA autologous CAR T therapies. And also two of the patients with scleroderma were treated with BCMA T cell engagers. And these patients responded to all these therapies. So really, the questions that we are wanting to discuss this video is one.

We thought that all these CAR T therapies are going to be eternity. Unfortunately, this is not the case, particularly in the field of autoimmune diseases. Secondly, success of treatment with BCMA therapies might pose the questions that should BCMA targeted at the first instance as an antigen in T cell therapies. And thirdly, these patients have had to go through, you know, the process of CAR T cell therapy in the beginning and with the median relapse of thirteen months and subsequently had to go different therapies, which is more intensive. We also have to pay attention in terms of safety profile, particularly long term reduction in terms of IgG level on infections.

So only time will tell. So I hope you found my video summary interesting about this progress. Follow us on, follow RheumNow on the social media outlets for more Congress content. Bye bye.

Hi, I'm Doctor. Janet Pope reporting At RheumNow at ULAAR twenty twenty six in London, England. I wanna talk about how many CAR Ts, cars do we need to test drive? And the reason I'm talking about this is there was a lot going on at this meeting on CAR T therapy. And in fact, I searched and there were 93 abstracts at ULAAR twenty twenty six that had CAR T in the title.

I also went to a wonderful session on June 5 on the What is New or Win session by Doctor. Hector Chanoi, and he talked about CAR T and inflammatory myositis. And many of the concepts that he talked about, I've tried to internalize to update all of us. So with this many abstracts, I think we know lots, but we have more questions than answers. So one of the first questions is, who should we select for treatment for CAR T?

I think in general the consensus would be certain diseases might do better than others such as lupus, maybe myositis would do better than maybe RA or systemic sclerosis. But I'm just giving you a gestalt. We really don't know within an individual. The other thing on selection that's important is we would like someone in general, the perfect candidate would be younger and not having comorbidity, high disease activity, low damage, and they haven't failed everything, but they have poor prognosis. So we know the writings on the wall say in a lupus nephritis patient who hasn't responded well at all in three months of triple therapy for lupus nephritis and is adherent.

Then the next question is, well, what do we want to inhibit? So there's a lot of CARs out there. So CD19, CD20, BCMA, NK cells, duo targets, even a triple target. I learned something called an armored CAR, which is a CD nineteen CAR T therapy, but also giving cytokine inhibition, which is supposed to increase the durability of the response. So which target to choose?

I don't actually know and I don't think that in these trials we know who will respond to what better. Then do we prime with chemo or not? And do we give leukapheresis? And leukapheresis will depend on the type of CARs. So if you're giving the traditional one that was around the longest autologous, you have to get the cells, cell sorts, so you get the CARs made against say CD19, if that's the target, and then you give chemo to get rid of all their cells, at least in the circulating compartment and some within organs as well.

So that's autologous and there's no graft versus host or anything like that because it's your own cells. But there's a timeframe where you wait. If it's not made right and the patient's off therapy, they might be flaring more or not because they've been primed with chemotherapy. There's allogeneic and it's kind of attractive because it's off the shelf. So we would assume in something like that, let's say again, we'll say the target is CD 19, that it would be a CAR that would look like most people's CD nineteen nineteen that they could basically be distributed and destroy the CARs, the the CD nineteens within the patient.

Then there's this new concept of endogenous. So in vivo, where you're popping it into the patient, it could be in vivo with mRNA vector, or even with viral delivery. The next issue really is safety, the short term and the long term. So it's important to know the timing of reactions. So cytokine release syndrome or CRS takes a few days to a week or two to occur in general.

The ICANS that's immune effector cell associated neurotoxicity syndrome, That's more severe. The patient can be attended having other neuro side effects. And that problem might actually need tocilizumab either CRS or ICANS might or might not need glucocorticoids. Then there's a new problem that's been described called LICATS, that's local immune effector cell associated toxicity syndrome. LICATS is a mouthful to think about, but it's more in our autoimmune connective tissue disease patients where they might have an organ wake up for a while that is transient, and the thought is it's when cells are coming up and then more normalizing over time.

But I'm not exactly sure why it occurs. Then what do we do if there's a recurrence? Do we have frozen, if it's autologous? Do we have frozen cells? Is the patient going to be resistant?

How long will it work for? And what will it work for? Will it work for every manifestation or just some? Will it work for lupus nephritis and not maybe for pain and fatigue? We don't know all that.

Then what to select in different diseases? Is there one optimal route of admin of like the autologous versus the allogeneic? Is it whatever you can get your hands on? Are we priming? And with that comes the new expectations.

So when I naively heard about CAR T therapy, when it first came in oncology, more than a decade ago, I thought, wow, this is amazing. It's a cure. It's quite a neat immune way to mop up a lymphoma or leukemia that has been recalcitrant to everything. And so the idea in CAR T back then was immune reset. Now they're talking about a new buzzword phrase, I hadn't heard it till this meeting called immune dimming.

And what that means is the immune system has improved, but you're not getting a patient say to remission and certainly not in drug free remission that you might have to restart something. Then a final long term concern, not for everybody, but there have been reports mostly again coming from the oncology literature of an increased risk of cancer years after getting CAR T therapy. But in oncology literature, the biggest risk of cancer is having had cancer. The next biggest risk is having had huge cocktails of chemotherapy. So I think we have a lot to think about, but if there's 93 abstracts just at this meeting, this is still a really exciting field.

And right now, I don't know many how many CAR Ts we need to actually test drive. Please follow me at Janet Burdope, and follow at RheumNow. Thank you.