OP0193 BITEING MULTI-DRUG RESISTANT RHEUMATOID ARTHRITIS WITH CD19-T CELL ENGAGERS (2024)

Abstract

Background: Bi-specific T-cell engagers (BiTEs) kill B cells by engaging T cells. BITEs are highly effective in acute lymphoblastic leukemia but have not yet been tested in autoimmune disease. Multi-drug resistant rheumatoid arthritis patients represent a considerable challenge and require new approaches to treat their underlying autoimmune pathology.

Objectives: Based on the action of BiTEs to kill B cells by engaging T cells as effectors we hypothesized that this principle may work also in the treatment of B cell mediated autoimmune diseases including RA.

Methods: We treated six patients with multi-drug resistant rheumatoid arthritis (RA) with two cycles of the CD19xCD3 BiTE blinatumomab via a compassionate use program. Eligibility criteria were based on (i) a diagnosis of RA according to the ACR/EULAR 2010 criteria, (ii) evidence for B cell involvement based on positivity of rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPA) or presence of B cells in the synovial membrane, (iii) active disease with a disease activity score (DAS) 28 over 3.2 units and (iv) treatment resistance to methotrexate and at least three different targeted synthetic (ts) or biologic (b) disease modifying anti-rheumatic drugs (DMARDs). Changes in circulating T and B cells were measured by high dimensional spectral flow cytometry and bioinformatic analysis. Serum cytokines were measured by solid-phase chemiluminescence assay. Ultrasound was performed in all patients at baseline and at 12 week follow-up and scored according to EULAR-OMERACT. Fibroblast activation protein inhibitor (FAPI)-based positron emission tomography/computed tomography (PET-CT) was performed in one patient at baseline and follow up. Ultrasound guided synovial biopsy and immunohistochemistry for quantification of B cells and plasma cells was performed in one patient at baseline and follow up.

Conclusion: These data demonstrate the principle feasibility to effectively treat B cell mediated autoimmune disease with BiTEs.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.