Effects of different B-cell-depleting strategies on the lymphatic tissue

OBJECTIVES: To assess the efficacy of new protein-based B cell depletion with glyco-engineered anti-CD20 antibody obinutuzumab (OBI) and the CD19/CD3 T cell engager blinatumomab (BLI) in patients with autoimmune diseases (AIDs) in comparison to rituximab (RTX) and CD19 chimeric antigen receptor (CAR) T cell therapy. METHODS: Sequential inguinal lymph node biopsies were taken before and after treatment with OBI-, BLI-, RTX- and CD19-CAR T cells in patients with AID. CD19+ and CD20+ B cells, plasma cells, T cells and macrophages were analysed by immunohistochemistry. Changes in follicular architecture (follicular dendritic cells, T follicular helper cells, proliferation) were also assessed. RESULTS: Baseline and follow-up lymph node biopsies from 24 patients with AID (OBI, 4; BLI, 4; RTX, 4; CD19-CAR T cells, 12) were analysed. B cell depletion was confirmed in all CD19-CAR T cell-treated patients but only in 1 (OBI) out of 12 protein-based B cell-treated patients. Likewise, follicular architecture was disrupted in all CD19-CAR T cell-treated patients but only in 1 (OBI) out of 12 protein-based B cell-treated patients. B cell depletion efficacy in the lymph nodes was 100% for CD19-CAR T cells, 92% for OBI, 86% for RTX and 69% for BLI. Plasma cells were reduced but not depleted in all treatment approaches. CD3+ T cells and CD68+ macrophages remained unaffected. Peripheral blood B cell depletion occurred in all but 1 BLI-treated patient. B cell depletion was associated with stable drug-free remission, whereas a reduction in B cell numbers without depletion required retreatment with immunomodulatory drugs. CONCLUSIONS: Protein-based B cell depletion reduces but usually does not deplete B cells in lymph nodes leaving the follicular architecture intact and being associated with disease recurrence.