ICML 2025 | The safety and efficacy of CAR T-cell therapy in the management of secondary CNS lymphoma

CAR T-cells are really exciting. You know, they’ve definitely been a focus of a lot of this conference because they provide a really interesting and efficient option for patients with systemic lymphoma in particular. Similar to bispecifics, there were initial questions as to whether or not the T-cells can effectively traffic and penetrate the CSF. So the initial trials actually also excluded patients with CNS lymphoma. But more recently, there have been data showing that actually CAR T-cells do in fact penetrate the CSF. So we had about 20 patients who got CAR T-cells with active secondary CNS lymphoma. And what we really found was that unfortunately CAR T-cells do not provide a long-term remission for these patients. We know that in patients with systemic lymphoma, CAR T-cells, in particular DLBCL, CAR T-cells can induce a long-term remission in maybe about 40% of patients. But in our particular study for secondary CNS lymphoma, that number was about 10%. So it did not yield a long-term response. And the rates of ICANS, in particular high-grade ICANS, so grade 3 and 4, were pretty high. So several patients had seizures, complications, probably due to the off-target effects of CD19. So I think, you know, in comparing CAR-T versus bispecifics, I think bispecifics are pretty interesting and neat in that they don’t have as much toxicity and that they didn’t have a lot of CRS and ICANS. And the duration of response was about five to six times longer than CAR T-cell. So I think that there’s still some work that needs to be done with CAR T-cells in terms of, you know, how they penetrate the CNS. Are there other agents we can give along with CAR-T to make them more efficacious in the CNS? It’s possible. But I think for now bispecifics in particular are really exciting as a new therapeutic option.

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