Durability of Antibody Removal Following Proteasome Inhibitor-Based Therapy

Background. Evidence of the short-term effect of bortezomib on donor-specific human leukocyte antigen (HLA) antibody (DSA) removal capacity has emerged. However, no published data characterize the durability of DSA response. Here, we report the long-term DSA response results on renal transplant patients treated with bortezomib. Methods. In this single-center study, 26 living-donor renal transplant patients with a positive level of de novo DSA were preemptively treated with bortezomib (1.3 mg/m(2) x 4 doses). A total of 15 patients received bortezomib as part of a combination regimen; 11 received bortezomib alone. Weekly serial measurements of HLA antibody were noted before, during, and after treatment using single-antigen beads. Results. At a median follow-up of 25.8 months posttreatment, allograft function remained good in each of the patients. Following treatment, 96% of the patients achieved at least a partial response. Eighteen patients (69%) experienced a complete response followed by a period of DSA remission. Ten patients had DSA relapse after remission, at a median of 3.8 months. The remaining eight patients are still in remission at 14 months posttreatment (median). Patients with remission enjoyed better allograft functional stability than those who relapsed (P = 0.023). After bortezomib therapy, the addition of a calcineurin inhibitor or mycophenolate mofetil was predictive for maintaining a DSA remission (hazard ratio 0.09, 95% confidence interval 0.01-0.76). Conclusions. Bortezomib therapy consistently provides reduction in DSA and in many a DSA remission may occur. However, sustaining remission is likely necessary to improve allograft stability.