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DOI: 10.1055/s-0042-1748725
Modulation of Daratumumab efficacy by Decitabine in pediatric T-cell lymphoblastic leukemia (T-ALL)
Aim: To examine the therapeutic efficacy of a combination of the hypomethylating agent Decitabine (Deci) with the CD38 antibody daratumumab (Dara) in pediatric T-ALL.
Methods: Surface expression of CD38 was determined after exposure to Deci in T-ALL cells (P12, Molt13, HSB2). Dara and Deci were administered as monotherapies and in combination in T-ALL cell lines and patient-derived xenograft (PDX) cells of pediatric T-ALL samples. Antibody-dependent effector mechanisms were examined in vitro.
Results: CD38 surface expression was significantly elevated in T-ALL cell lines subjected to Deci. Moreover, antibody-dependent cell-mediated cytotoxicity (ADCC) by mononuclear cells and antibody-dependent cellular phagocytosis (ADCP) by macrophages were significantly enhanced in T-ALL-cells subjected to combined treatment with Deci and Dara. Notably, ADCP was also elevated in eight de novo and six relapsed/refractory (r/r) T-ALL PDX samples after combination treatment as compared to single therapy.
Conclusion: Dara combined with Deci may represent a promising therapy approach for T-ALL, especially in case of r/r disease, and potentially other hematological malignancies of a T-cell origin.
Publication History
Article published online:
17 May 2022
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