Background

Several studies demonstrated bortezomib therapy for antibody-mediated rejection (AMR) in renal transplants. However, the treatment efficacy according to target antigen or occurrence time of AMR has not been identified. We describe our experience with bortezomib used to treat AMR in ten renal transplant patients.

Methods

Ten patients who received bortezomib for treatment pure AMR were included in this study. The presence of donor specific anti-HLA antibodies was determined using single antigen beads assay utilizing the multiplex flow-bead microarray method . All patients were treated and did not respond to conventional treatment composed of plasmapheresis with intravenous immunoglobulin + rituximab. Patients received one to two cycles of bortezomib (4×1.3 mg/m² per cycle). Early AMR was defined as occurring within 6 months post-transplant.

Results

A total of eleven episodes were treated with bortezomib (6 early and 5 late). One patient had anti-ABO antibody with anti-HLA antibody. Another patient had no anti-HLA antibody, but had a high titer of anti-angiotensin II type 1 receptor antibodies.

All episodes of early onset AMR were fully recovered after 1 cycle of bortezomib treatment regardless of target antigen. Three of five late onset AMR episodes responded to bortezomib. Overall, there was a significant improvement in mean estimated glomerular filtration rate at the end of therapy as compared to the eGFR at the time of diagnosis (p=0.005). Bortezomib related toxicities (thrombocytopenia and peripheral neuropathy) were all transient and recovered with conservative management.

Conclusion

Bortezomib can be an effective treatment for refractory AMR regardless of target antigen.

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