EHA 2025 | CD33-deleted allograft enables gemtuzumab ozogamicin maintenance post-transplant in AML

There’s an unmet need of patients with high-risk cytogenetics such as biallelic TP53 mutation and monosomy 5 or 8. And therefore, our strategy focuses on improving the outcome of these patients. To answer your question, there is a limitation of specifically targeting acute myeloid leukemia cells based on the fact that markers expressed on the leukemia cells are also expressed on the normal hematopoietic stem cell. And therefore, you would affect both cell populations by specifically targeting the leukemia cell population. Now CD33 has been described as abundantly overexpressed on leukemic cell populations, but also on normal hematopoietic stem cells. But it may not be needed for normal neutrophil and platelet engraftment. And in our study, we can show exactly that, that if we transplant patients with CRISPR-Cas9 edited hematopoietic stem cells, deleting the expression of CD33 and therefore resulting in CD33 negative, CD34 positive transplant product that we can achieve a normal time to engraftment, neutrophil engraftment day 9, platelet engraftment day 14 without having any adverse effects with respect to that one. Which then will allow to test the administration after transplantation of an anti-CD33 monoclonal antibody such as gemtuzumab to allow to specifically target the leukemic cell population. But the key question that you ask and that is so relevant, does gemtuzumab post-transplantation in this setting induce side effects? Because we have known from previous studies that gemtuzumab, in addition with 7 plus 3, has side effects in terms of liver toxicity and inducing low counts, sometimes low neutrophil or even pancytopenia. And we can show in the study that this is not the case. So in other words, this transplant product that we call a shielded transplant product is not affected by gemtuzumab because the cells derived from the CD33 negative stem cells are not expressing CD33 and therefore not targeted by gemtuzumab. So that’s a big step forward to have this methodology in place and saying, okay, CD33 negative transplant products do not affect the neutrophil and platelet engraftment and gemtuzumab administration starting at day 60 as per protocol as of now does not have side effects in terms of liver toxicity or engraftment effects on neutrophil or platelet counts.

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