Klin Padiatr 2022; 234(03): 184-185
DOI: 10.1055/s-0042-1748725
Abstracts

Modulation of Daratumumab efficacy by Decitabine in pediatric T-cell lymphoblastic leukemia (T-ALL)

M-P Autenrieb
1   Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
F Vogiatzi
1   Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
D Winterberg
1   Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
CL Gelehrt
2   Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
L Lenk
1   Pediatric Hematology/Oncology, ALL-BFM Study Group, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
N Baumann
2   Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
S Wolf
3   Department of Pediatrics, Otto-von-Guericke University Magdeburg, Magdeburg Germany
,
T Valerius
2   Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
M Peipp
2   Division of Stem Cell Transplantation and Immunotherapy, Department of Medicine II, Christian Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
DM Schewe
3   Department of Pediatrics, Otto-von-Guericke University Magdeburg, Magdeburg Germany
› Author Affiliations
 

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

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany