What Happens when CAR-T Fails Managing Disease Recurrence Save

Hey there, my name is Al Kim. I'm at EULAR 2026 in London, UK. And I wanted to bring up another topic within the cellular therapy space that I found very interesting — two different abstracts about 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, that was provided by Dr. Andreas Versing, entitled "Management of Relapses After Autologous CD19 CAR T Cell Therapy in Lupus, Scleroderma, and Inflammatory Myopathies: A Case Series." And then the second one, another oral abstract, OP 333, that was presented by Dr. Dimona Ning, 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 these are two reports coming from Erlangen. All right, so Erlangen has probably the most patients at a single center that has treated autoimmune diseases with either a 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 an autologous source.

And so here, from a single product, they have 50 patients that were treated, and out of those 50, pretty remarkably, only six have demonstrated a relapse. And it's not the same across all autoimmune diseases. In lupus, they had one out of 28 with a relapse. In scleroderma, they had two out of 14 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 13 months.

And what is 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 10 months, another one at 18 months after getting the first CAR T cell therapy — two of them got a BCMA CAR T cell. 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 plasmablasts 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 about 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 plasmablasts, or that there are pathogenic B cells that aren't making antibodies — and lupus is the best example of this. And again, this Erlangen experience highlights that only one out of 28 relapsed with the CD19 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. 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 tofacitinib 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 — this participant got obinutuzumab plus nintedanib, 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 the exception of a mild rash that was treated with anifrolumab, and then the patient went into remission after that. The two patients with scleroderma — one of them relapsed at 16 months, the other one at 24 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 apparently coming 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 off the bat, 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 100% have hypogammaglobulinemia and a higher rate of infections — I guarantee you that. Is this something that your patient will want to sign off on when the majority — all right, we're talking nearly 90% of patients treated across the spectrum, at least in the Erlangen experience across different diseases — responded to just CD19, where you don't have to worry about hypogammaglobulinemia or those infections? So it's an interesting question.

So the second abstract —
presented by Dr. or anything um was a case report of one of these lupus patients in a uh different study. Um there were 11 patients with uh lupus that were received CD19 CAR T cells. One of them relapsed um at day 226 um uh clinically um after getting CD19 CAR T cells.

Now, interestingly in this particular person, several days before she actually had a routine uh per protocol collection of her blood and they did immunologic analysis of that preclinical flare uh um uh 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 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 um rises in autoantibody levels that then end up having uh you know allow you to anticipate clinical uh relapse right so you know again this is an in 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 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 you know predict whether or not someone will relapse clinically and then you can get ahead of the game. Thanks.