EHA 2025 | Early findings on donor-derived anti-CD33 CAR T-cells in R/R AML after alloSCT

Well, the principal idea to use the shielded transplant product as described, CD33-negative, CD34-positive hematopoietic stem cells, will then also allow to test the administration of donor-derived CD33-directed CAR T-cells in the event of relapse after transplantation. And as I pointed out earlier, TP53 mutated AMLs are at high risk to relapse. And therefore, we may have here an alternative approach to treat relapsed disease in this setting with the CAR T-cells. Now, we have limited cases to treat at this time point patients treated with the CAR T-cells after relapsing with this gene-edited product. But I got lucky to be the first physician that had the opportunity to provide a patient that relapsed after CD33 deleted or gene-edited transplant product with another therapeutic approach, such as to infuse the patient at relapse with the donor-derived CD33-directed CAR T-cells. And I’m happy to report that this patient went from 40% of blasts within a few days to a complete remission. This remission lasted as of now up to six months, molecularly negative, flow cytometry negative. So it’s a deep, sustained, complete remission, proving at least the principle that post-transplantation CAR T-cells after gene-edited transplants may be a real alternative for patients with high-risk acute myeloid leukemia, including like this patient with biallelic TP53, monosomy 5 and monosomy 8.

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