AT A GLANCE

A new study published in Annals of the Rheumatic Diseases reports that protein-based B-cell depletion reduces but usually does not deplete B-cells in lymph nodes, contrasting with the consistent full depletion of B-cells seen following CD19–chimeric antigen receptor (CAR) T-cell therapy.¹

“Advanced protein-based B-cell depleters, such as [the] glycoengineered CD20 monoclonal antibody obinutuzumab (OBI) and [the] CD19/CD3 T-cell engager blinatumomab (BLI), are promising new therapeutic instruments for treatment of autoimmune disease. It has been speculated that such B-cell–depleting modalities achieve better clearance of tissue B-cells in patients,” explain study authors Tur et al., who sought to assess the efficacy of OBI and BLI in patients with autoimmune diseases compared to rituximab (RTX) and CD19-CAR T-cell therapy.

The authors enrolled 24 patients with autoimmune diseases and collected sequential inguinal lymph node biopsies both before and after treatment with OBI-, BLI-, RTX-, and CD19-CAR T-cells. Subsequently, CD19+ and CD20+ B-cells, plasma cells, T-cells, and macrophages were analyzed by immunohistochemistry, and changes in follicular architecture (follicular dendritic cells, T follicular helper cells, proliferation) were also assessed.

According to the authors, baseline and follow-up lymph node biopsies from 24 patients with autoimmune diseases—including four who received OBI, four who received BLI, four who received RTX, and 12 who received CD19-CAR T-cells—were analyzed.

Although B-cell depletion was confirmed in all CD19-CAR T-cell–treated patients, just one of the 12 protein-based B-cell–treated patients, who received OBI, showed the same. Likewise, follicular architecture was disrupted in all CD19-CAR T-cell–treated patients but in only one of the 12 protein-based B-cell–treated patients, who similarly received OBI.  

Other analysis showed that B-cell depletion efficacy in the lymph nodes was 100% with CD19-CAR T-cell therapy, 92% with OBI, 86% with RTX, and 69% with BLI. Plasma cell concentrations were reduced but not depleted following all treatment modalities, while those of CD3+ T-cells and CD68+ macrophages remained unaffected.

Peripheral blood B-cell depletion occurred in all but one BLI-treated patient.

“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,” conclude the authors. “These results stand in contrast to the consistent full depletion of B-cells associated with the disruption of follicular lymph node architecture after CD19-CAR T-cell therapy.”

Reference

1.     Tur C, Eckstein M, Bucci L, et al. Effects of different B-cell-depleting strategies on the lymphatic tissue (online ahead of print July 11, 2025). Ann Rheum Dis.