Treatment of antibody-mediated rejection (AMR) in renal transplant (tx) patients (pts) is still challenging and long-term outcome remains unsatisfying. Because plasma cells (PCs) are crucial for donor specific HLA antibody (DSA) formation, targeting this cell population with bortezomib (BZ) is quite reasonable. Combination of BZ with the B-cell depleting rituximab (Ritux) may display synergistic effects on precursor and mature DSA producing cells.

The aim of this study was to evaluate the efficacy and safety of three different AMR therapy regimens with Ritux (n=12, group A), BZ (n=23, group B) or Ritux+BZ (n=10, group C).

45 tx pts (men:29) with graft dysfunction, DSA and biopsy proven AMR according to BANFF classification were included into the study, starting in 1/2005. All pts received steroid pulse and PPH (6x). In addition, group A received a fixed dose of Ritux 500mg and IVIG 30g. Group B received 1 cycle of BZ (1.3 mg/m2; day 1, 4, 8, 11) and IVIG (30g; n=11 or 1.5g/kg; n=12). Group C received a combination of Ritux 500mg and one cycle of BZ with high dose IVIG. Pts had a mean follow-up of 59 (SD+/-22.5) months (m).

Cumulative pt survival was 94.3% in the follow-up. One pt died due to unknown cause 23m after treatment (group A) and one pt died from MI 33m after AMR therapy (group B). In general, graft survival was inferior in group A (1/12; 8.3%) as compared to group B (9/23; 39.1%; p=0.04) and group C (6/10; 60%; p=0.02) at the end of follow-up time. However, between group B and C, no significant difference was seen concerning graft survival. Notably, in group C adverse events, in particular infections were more dominant compared to both other groups.

This retrospective cohort study demonstrated significantly better graft survival following treatment of AMR with BZ or Ritux+BZ compared to Ritux alone in the long-term follow-up. The additional use of Ritux in combination with BZ showed no additional effect, but an increased incidence of side effects. Further randomized trials need to be performed to obtain more data on such a synergistic approach.

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