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Abstract: FR-PO1076

Persistent B-Cell Depletion After Rituximab

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Chen, Debbie, MGH, Boston, Massachusetts, United States
  • Wallace, Zachary S., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Rosenthal, Jillian, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Sipilief, Alexander Theodore, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Laliberte, Karen A., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Niles, John, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Cortazar, Frank B., Massachusetts General Hospital, Boston, Massachusetts, United States
Background

Rituximab (RTX), an anti-CD20 monoclonal antibody, is an effective therapy for many glomerular diseases. Following RTX, B cell reconstitution occurs at a median of 8 months, and the vast majority of patients have B cell return by 18 months. We report 7 patients with autoimmune kidney disease who developed persistent B cell depletion following RTX.

Methods

We performed a retrospective analysis of patients with glomerular disease treated with rituximab between 2006-2017. Patients who had persistent B cell depletion, defined as undetectable CD20+ B cells determined by flow cytometry for > 2 years after their last rituximab dose, were included in the study. Patient characteristics, serological markers of disease, adverse events, and survival were examined.

Results

We identified 7 patients with persistent B cell depletion. Six patients were treated for ANCA vasculitis and one for lupus nephritis. Patients received a median of 13 RTX doses (range, 5 to 22). Following the final RTX, B cells in these patients have remained undetectable for a median of 5.2 years (range, 3.9 to 6.9). Four patients developed significant hypogammaglobulinemia (IgG < 400 mg/dL) and two received IVIG. RTX-induced late-onset neutropenia occurred in 3 patients. Five patients developed serious infections and one patient died in the setting of infection associated with recurrent late onset neutropenia. No patient had recurrence of their underlying autoimmune disease.

Conclusion

Persistent B cell depletion after rituximab is a rare but important complication of therapy that appears to be associated with late-onset neutropenia and serious infections. The mechanism of this phenomenon is unclear. Additional investigation into the risk factors and pathogenesis of this complication are needed.

Patient and Outcome Characteristics
AgeGenderDiseaseYears of B cell depletion# rituximab dosesSignificant hypogammaglobulinemiaIVIG givenLON episodesMajor infections
61MMPO ANCA3.922NoNo0Recurrent sinusitis
67MMPO ANCA4.213NoYes22Neutropenic sepsis
50MPR3 ANCA6.221YesNo0None
43FSLE6.97YesYes3Recurrent gastroenteritis, colitis
62MMPO ANCA6.913NoNo0Recurrent pneumonia
34FMPO ANCA5.25YesNo4Recurrent sinusitis
60FMPO ANCA3.99YesNo0None

LON: late onset neutropenia Major infections: infection leading to hospitalization or requiring intravenous antibiotics