CD38-targeted therapy with daratumumab reduces autoantibody levels in multiple myeloma patients

Kristine A Frerichs; Christie P M Verkleij; Patricia W C Bosman; Sonja Zweegman; Henny Otten; Niels W C J van de Donk

doi:10.1016/j.jtauto.2019.100022

CD38-targeted therapy with daratumumab reduces autoantibody levels in multiple myeloma patients

J Transl Autoimmun. 2019 Nov 11:2:100022. doi: 10.1016/j.jtauto.2019.100022. eCollection 2019 Dec.

Authors

Kristine A Frerichs¹, Christie P M Verkleij¹, Patricia W C Bosman¹, Sonja Zweegman¹, Henny Otten², Niels W C J van de Donk¹

Affiliations

¹ Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Cancer Center Amsterdam, Amsterdam, the Netherlands.
² University Medical Center Utrecht, Laboratory of Translational Immunology, Utrecht, the Netherlands.

Abstract

Autoantibody-producing plasma cells are frequently resistant to conventional immunosuppressive treatments and B-cell depletion therapy. As a result of this resistance, autoreactive plasma cells survive conventional therapy, resulting in persistent autoantibody production and inflammation. CD38 is highly and uniformly expressed on normal and malignant plasma cells. Daratumumab is the first in class CD38-targeting monoclonal antibody approved for the treatment of multiple myeloma (MM). To evaluate the potential activity of daratumumab in antibody-mediated autoimmune disorders by targeting autoantibody-producing plasma cells, we evaluated serum levels of autoantibodies in MM patients during daratumumab treatment. We found that 6 out of 41 (15%) had detectable autoantibodies before initiation of daratumumab therapy, and that these autoantibodies rapidly disappeared in 5 out of 6 patients during daratumumab treatment. Our data provide support for the evaluation of daratumumab in patients with autoantibody-dependent autoimmune disorders.

Keywords: Antibody-mediated autoimmune disease; Autoreactive; CD38; Daratumumab; Plasma cells.