BiTEing Multi-drug Resistant Rheumatoid Arthritis with CD19-T Cell Engagers

Abstract Text: Bi-specific T-cell engagers (BiTEs) kill B cells by engaging T cells. BITEs are highly effective in acute lymphoblastic leukemia. We treated six patients with multi-drug resistant rheumatoid arthritis (RA) with the CD19xCD3 BiTE blinatumomab. Low doses of blinatumomab led to B cell depletion and concomitant decrease of T cells, documenting their engager function. Treatment was safe, with brief increase in body temperature and acute phase proteins during first infusion but no signs of clinically relevant cytokine-release syndrome. Blinatumomab lead to a rapid decline in RA clinical disease activity, improved synovitis in ultrasound and FAPI-PET-CT and reduced autoantibodies. High dimensional analysis of B cells documented an immune reset with depletion of activated memory B cells, which were replaced by non-class switched, IgD positive naïve B cells. Together, these data demonstrate the principle feasibility to effectively treat B cell mediated autoimmune disease with BiTEs.