What is the recommended management for antibody-mediated rejection (AMR) in lung transplant recipients?

Management of Antibody-Mediated Rejection (AMR) in Lung Transplant Recipients

The recommended first-line treatment for antibody-mediated rejection in lung transplant recipients should include high-dose corticosteroids, plasmapheresis, intravenous immunoglobulin (IVIg), and rituximab. 1

First-Line Treatment Protocol

• High-dose corticosteroids (methylprednisolone 500-1000 mg IV daily for 3 days) should be initiated immediately upon diagnosis of AMR to reduce inflammation and immune response 1
• Plasmapheresis should be performed daily or every other day for a minimum of 5 sessions to mechanically remove circulating donor-specific antibodies (DSAs) 1, 2
• IVIg (2 g/kg divided into doses) should be administered after plasmapheresis sessions to provide passive immunity and immunomodulation 1, 3
• Rituximab (375 mg/m² weekly for up to 4 doses) should be added to target B cells responsible for antibody production 1, 4

Second-Line Therapy for Refractory Cases

• Bortezomib (1.3 mg/m² on days 1,4,7, and 10) should be added for cases not responding to first-line therapy as it targets plasma cells 1, 4
• Anti-complement antibodies (such as eculizumab) may be considered for severe or persistent cases of AMR to block complement activation 5, 1
• Total lymphoid irradiation or photopheresis may be considered for refractory cases that fail to respond to other therapies 5, 1

Optimization of Maintenance Immunosuppression

• Consider switching from cyclosporine-based immunosuppression to tacrolimus to improve outcomes 5, 1
• Consider increasing the dose of mycophenolate mofetil (MMF) or substituting with sirolimus to optimize maintenance immunosuppression 5, 1
• Cyclophosphamide (0.5-1 g/m² every 3 weeks for 4-6 months) may be considered as an alternative to MMF in severe cases 5, 1

Treatment Monitoring and Efficacy

• Follow-up biopsies should be performed to assess histological improvement 1
• Monitor DSA levels to evaluate treatment response, with a goal of complete or significant reduction in DSA levels 2, 6
• Studies show that combined PLEX and IVIg protocols result in improvement in AMR on biopsy in approximately 69% of patients and a decline in DSA in 68% of patients 2

Institutional Protocols and Evidence

• The most commonly used regimen in clinical practice consists of plasmapheresis, IVIg, and rituximab (49.1% of cases), followed by IVIg and plasmapheresis alone (27.3%) 3
• Standardized protocols using 5 plasmapheresis sessions with IVIg have shown efficacy in reducing DSAs and improving AMR in lung transplant recipients 2, 6
• More aggressive protocols (8 plasmapheresis sessions with IVIg and bortezomib) may be necessary for predicted non-responders based on pre-treatment DSA characteristics 6

Potential Complications and Considerations

• Common complications of treatment include thrombocytopenia (50%) and gastrointestinal discomfort (18.7%) 4
• Careful monitoring of hemodynamic parameters during plasmapheresis is essential to prevent complications 7
• The severity of AMR (based on histopathology, C4d staining, and DSA levels) should guide the intensity of treatment 1

Treatment Response Predictors

• Mean fluorescence intensity (MFI) in pre-treatment diluted sera (1:16) can predict response to standardized treatment protocols and patient survival 6
• Patients with high MFI values may require more aggressive treatment approaches from the beginning 6