Persistent B Cell Depletion After Rituximab for Autoimmune and Glomerular Diseases: A Case Series

Persistent B cell depletion is a rare complication of rituximab treatment, and its clinical implications are unknown.

This retrospective case series included patients with glomerular and autoimmune diseases who developed persistent B cell depletion (< 5 CD19⁺CD20⁺ cells/μl persisting for > 2 years) after the last rituximab dose.

Among 1519 patients who received rituximab, 2% (n = 30) had persistent B cell depletion. The frequencies of persistent B cell depletion were 2.5% (22 of 878), 2.4% (2 of 82), and 0.8% (1 of 114) in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), systemic lupus erythematosus (SLE) or lupus nephritis, and podocytopathies, respectively. The remaining patients had ANCA-negative vasculitis (n = 2), anti-glomerular basement membrane disease (n = 1), Behcet's disease (n = 1), and polymyositis (n = 1). The median age was 64.5 (interquartile range [IQR]: 44-77) years. Before the last dose of rituximab, all patients except 2 used cytotoxic agents, often prolonged (> 1 year) or recycling courses, and 60% (18 of 30) received a period of long-term maintenance steroids. By 4 years after the last rituximab dose, only 30% had B cell repopulation. In those who experienced B cell repopulation, B cell counts remained very low, at a median of 7(6-15) cells/μl at the last follow-up. After the last rituximab dose, 83% (23 of 30) had sustained disease remission. Late-onset neutropenia, recurrent infections, and severe infections occurred in 23% (7 of 30), 47% (14 of 30), and 57% (17 of 57), respectively. Of the patients, 23% (7 of 30) required immunoglobulin replacement, and 30% (9 of 30) died, mostly from complications of chronic diseases.

Persistent B cell depletion is a rare complication of rituximab treatment, mostly affecting patients with exposure(s) to cytotoxic therapies for recurrent diseases. It is characterized by prolonged disease remission and increased infection risk.