SP687DO WE KNOW HOW TO TREAT RESISTANT ANTIBODY-MEDIATED REJECTIONEFFECTIVELY? A SINGLE CENTRE EXPERIENCE

Abstract

Introduction and Aims: Acute antibody-mediated rejection (AMR) remains one of the major barriers to successful long-term outcomes. Previously reported therapeutic superiority of combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIG) may however fail in some resistant cases. Thus, the aim of this work was to analyze the efficacy and safety of administration of bortezomib (B) and rituximab (RTX)-based treatment of resistant AMR. Method(s): We retrospectively analyzed documentation of 772 patients who underwent renal transplantation between 1/2012-6/2015. Novel therapeutic approach to resistant acute AMR in kidney transplant recipients was applied in 23 patients (3%) based on administration of B [1 cycle of 4 doses of B (1.3 mg/m2)], small doses of i.v. corticosteroids, PP and a dose of RTX (375mg/m2). This protocol was administrated after conventional treatment had failed. Resistant AMR was defined as a persisting deterioration or non-function of renal allograft in patients with histological verification of AMR, positive C4d staining and detection of donor specific antibodies (DSA) receiving standard antirejection treatment with PP + IVIG. Patients (pts) were followed for 6-48 months. Result(s): Therapy of resistant acute AMR was administered to 23 pts after kidney transplantation with median peak PRA 52%, actual PRA 36%, mean HLA mismatch in HLA-A 1.2 +/- 0.4, HLA-B 1.7 +/- 0.5, HLA-DR 1.3 +/- 0, with median of 5.8 years on dialysis. 3 pts underwent 1st kidney transplantation, while 20 patients retransplantation (2nd Tx n=10, 3rd Tx n=6, 4th Tx n=4). Immunosuppressive protocol consisted of induction with antithymocyte globulin (n=22) or basiliximab (n=1). Diagnosis of resistant acute AMR was made on 14.th POD. Based on therapeutic effect, 15 pts received 1, 7 pts 2 cycles and 1 patient was treated with 3 cycles of B. We observed DGF in 26.1%. Using B regimen in treating resistant acute AMR led to decrease in DSA quantity in HLA especially in class I (p=0.005), class II (p = 0.015), but not in DQ (p= 0.2). No significant improvement of renal function was observed during the follow-up. The pts with the levels of serum creatinine increased more than 25% of baseline level in 6 months after administration of protocol with B, are progressors (n=7). The progressors graft survival was 57% in 20 months. The quantity of MFI DQ antibodies was significantly higher than in pts with stable renal function (non progressors). The side-effects observed were UTI (35%), colitis (13%), polyneuropathy (26%), hepatotopathy (13%), fluid retention (22%), thrombocytopenia (78%), leucopenia (56.5%), sepsis (30.4%). Conclusion(s): Traditional AMR therapeutic strategies have focused on antibody removal and B-cell depletion while not directly focusing on plasma cell depletion. Bortezomib was effective against HLA I and II class antibodies, the problem with DQ antibodies is still unsolved. Bortezomib-related toxicities were all transient. (Figure Presented).