Outcomes of CD19-directed CAR T-cell therapy in five individuals with multiple sclerosis

I presented our five individual treatment cases that were treated at our center with the Kyv-101 product, which is a CD19-directed CAR, a second generation with a CD28 co-stimulatory domain. We did one patient with secondary progressive MS, one patient with primary progressive MS, and three patients with relapsing-remitting MS. And we showed, which was the main message from our preliminary data of this really heterogeneous and mixed group and heavily refractory group of patients, that even though all of these patients were refractory to CD20 monoclonal antibodies, we saw that they all of them, even though that was a real issue, the fear of a heavily neurotoxicity, we showed that all of them only experienced mild grade CRS and no ICANS at all. We treated the CRS with tocilizumab, anakinra, and dexamethasone, and we showed an expansion-dependent effect on the oligoclonal bands, as we saw like four of the five patients had a good cortical expansion within the peripheral blood, and one patient did expand really poorly, and the oligoclonal bands rapidly decreased in four of the five patients, and the one patient that did not expand adequately, that didn’t show any movement of the oligoclonal bands. So this kind of indicates that the CAR-T cells have an expansion-dependent effect. I although have to mention that after their nadir, the oligoclonal bands seem to increase afterwards. We are still looking into that with more translational research. And we also saw from a clinical point of view the EDSS, the Expanded Disability Score, we saw that there was a slight, in one patient a slight increase, which was during the in-patient stay due to an Uhthoff phenomenon and also due to the immobilization during in-patient stay, which is going to be an issue, I think, during exploring CAR-T cell therapy in MS patients, because immobilization and Uhthoff phenomenon is going to be an issue. And then also we saw a decrease after discharge, then we saw a secondary increase above the baseline. We’re still looking into it. It’s important to say that all of these data is generated from a really heterogeneous group, and especially this patient that had an EDSS progression had a 23-year history of MS. So to just put this into perspective. And then we saw also in three patients non-enhancing MRI lesions, really small spinal MRI lesions at different time points without a clinical correlate. And it’s important to mention that the etiology of these kind of lesions is unknown, and we are still unsure or unclear what these lesions are interpreted in. There are different interpretations also because we didn’t do an MRI. This was not a clinical study, this was an individual treatment attempt, and we didn’t do an MRI right before the infusion. So it could also mean that these lesions are old lesions that kind of were detected after CAR T-cell infusions and necessarily are not in relation to the infusion. It could also be that these lesions are actually part of the CAR T-cell infiltration because we saw, which was also remarkable, despite not seeing any neurotoxicity in the form of ICANS, we did see an infiltration of the CAR T-cells within the CSF, which hasn’t been described yet. I mean, it could be a general phenomenon because obviously, like lumbar puncture is only performed in patients with heavily ICANS. So therefore, this further study needs to be done, and it needs to be investigated further. The general message that our data is giving us is that CD19-directed CAR T-cell therapy in MS patients is safe and can be performed, and there’s further data that needs to be studied.

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