Targeted Alpha Therapy (TAT) in AML: CD38 as a Promising Alternative to CD33

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,