Acute Myeloid Leukemia (AML) is the most common leukemia in adults, characterized by a poor prognosis and a 5-year survival rate below 30%, largely due to chemoresistance.
Targeted alpha-therapy (TAT) has emerged as a promising approach for treating disseminated tumors such as AML. Clinical trials using a [225Ac]Ac-anti-CD33 monoclonal antibody (mAb) have demonstrated encouraging responses, as CD33 is expressed in 85-90% of AML cases. However, this approach is frequently associated with prolonged myelosuppression, primarily due to CD33 expression on normal hematopoietic cells. To broaden therapeutic options while minimizing off-target toxicity, we explored CD38 as an alternative and innovative target. CD38 is a well-established therapeutic antigen in multiple myeloma, where daratumumab, an anti-CD38 mAb, has shown remarkable efficacy. Although CD38 expression in AML is heterogeneous, daratumumab has demonstrated only modest anti-tumor activity in this context. We hypothesize that using [225Ac]Ac-anti-CD38 mAb for TAT could overcome these limitations and provide a novel therapeutic strategy for AML, particularly in patients with higher CD38 expression than CD33.
SORIN M;
GOUARD S.;
MARIONNEAU-LAMBOT S;
MAINGUENEAU C;
MORGENSTERN Alfred;
BRUCHERTSEIFER Frank;
CHEREL M.;
HADDAD Ferid;
ALLARD M;
GASCHET J;
2025-11-07
Elsevier
JRC143755
1619-7089 (online),
https://www.sciencedirect.com/science/article/pii/S3051291325000047,
https://publications.jrc.ec.europa.eu/repository/handle/JRC143755,
10.1016/S3051-2913(25)00004-7 (online),
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