TY - JOUR
T1 - CD38-targeted therapy with daratumumab reduces autoantibody levels in multiple myeloma patients
AU - Frerichs, Kristine A.
AU - Verkleij, Christie P.M.
AU - Bosman, Patricia W.C.
AU - Zweegman, Sonja
AU - Otten, Henny
AU - van de Donk, Niels W.C.J.
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
KW - Antibody-mediated autoimmune disease
KW - Autoreactive
KW - CD38
KW - Daratumumab
KW - Plasma cells
UR - http://www.scopus.com/inward/record.url?scp=85089764935&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jtauto.2019.100022
DO - https://doi.org/10.1016/j.jtauto.2019.100022
M3 - Article
SN - 2589-9090
VL - 2
JO - Journal of Translational Autoimmunity
JF - Journal of Translational Autoimmunity
M1 - 100022
ER -