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Editorials
Table 1. List of conditions in which daratumumab has been reported to be clinically beneficial.
Condition
Post-allogeneic stem cell transplantation hemolysis/ cytopenia
Post-allogeneic stem cell transplantation pure red cell aplasia
Autoimmune hemolysis
Antibody-mediated rejection of transplanted kidney Antiphospholipid syndrome
Systemic lupus erythematosus
Proliferative glomerulonephritis
involved multiple coordinating cells such as systemic lupus erythematous, and proliferative glomerulonephritis (Table 1). The multiple aberrant immune mechanisms potentially involved make it difficult to identify the exact mechanisms of action of daratumumab in such conditions. Notably, a recent alarming report described that patients with COVID-19 can produce autoantibodies targeting CD38 which lead to exacerbation of immune responses resulting in autoimmune thyroiditis, insulin-dependent diabetes and even exacerbating the cytokine storm and other deleteri- ous responses in COVID-19.10
Daratumumab is an effective anti-myeloma agent with a low toxicity profile. Its prominent effect is elimination of CD38-bearing cells, and in myeloma patients it targets mostly malignant plasma cells. The current report by Crickx et al. suggests that it should be considered as a ther- apeutic option in refractory cases of ITP and warm AIHA. A proposed mechanism of action is similar to that in myeloma, i.e., elimination of antibody-producing cells, but since CD38 is presented by many other immune cells, potential ‘off-target’ effects cannot be ruled out. Daratumumab's potential effectiveness against T-cell acute lymphoblastic leukemia is to be investigated in a future, planned, prospective study. The work by Crickx et al. is a step forwards in recognizing the potential role of daratu- mumab in autoimmune conditions. However, this treat- ment should be used with caution because its effect on multiple arms of the immune system may lead to paradox- ical responses.
Reference
Blood. 2016;128:4819
Blood Advances 2018;2(19):2550-2553
British Journal of Haematology 2019;187(2): e48-e51 Pediatric Blood & Cancer 2021;67(1):e28010.
Blood Advances 2020;4(5): 815.
Molecular and Cellular Pediatrics 2021;8(1):1-7. Frontiers in Immunology 2021;12:444..
New England Journal of Medicine 2018;379(19):1846-1850 American Journal of Hematology 2019;94(8):E216-E219. Bone Marrow Transplantation 2020;55(6):1191-1193. European Journal of Haematology 2020;104(2):145-147
Acta Haematologica 2021;Apr 22;1-5 [Online ahead of print]
Transfusion 2019;59:3801-3802
American Journal of Hematology 2020 Jul 11 Annals of Hematology 2021;100(5);1351-1353
Case Reports in Nephrology and Dialysis 2019;9(3): 149-157 Frontiers in Immunology 2021;12:1133
New England Journal of Medicine 2020;383(12):1149-1155.
Journal of the American Society of Nephrology 2021;32 (5): 1163-1173
Disclosures
No conflicts of interest to disclose.
References
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2. van de Donk NW, Janmaat ML, Mutis T, et al. Monoclonal antibod- ies targeting CD38 in hematological malignancies and beyond. Immunol Rev. 2016;270(1):95-112.
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