Systematic Review of Bortezomib-based Desensitization Therapy in Sensitized Kidney Transplant Candidates: Efficacy, Safety, and Clinical Outcomes

Abstract

Objective: Highly sensitized kidney transplant candidates, those with high levels of antihuman leukocyte antigens antibodies, are at increased risk of antibody-mediated graft rejection. The goal of desensitization therapy is to reduce alloantibody titers and increase the chance and success of transplantation. The proteasome inhibitor bortezomib, which acts against plasma cells, has been reported to be an effective agent in this setting. This systematic review evaluates the efficacy and safety of bortezomib-based desensitization regimens in sensitized kidney transplant recipients. Methods: A systematic search of various databases was conducted between January 2005 and July 2025. Studies that considered sensitized kidney transplant candidates treated with bortezomib-based desensitization were included, and outcomes included reduction in donor-specific antibodies (DSA), engraftment rate, graft rejection, and adverse events. Findings: A total of 21 studies involving about 185 patients were included, comprising 11 case reports, 6 case series, and 4 clinical trials or prospective studies. Overall graft success rate was 87 rejection-free outcomes 76 and no more adverse events in 81. While most studies showed significant DSA reduction, one reported limited effectiveness. Bortezomib was generally well-tolerated, with no major adverse events in approximately 81 of studies. Mild neuropathy was noted in some cases, and treatment discontinuation occurred in 20 of patients in one trial. Conclusion: It can be concluded that bortezomib-based therapies are a potentially effective and well-tolerated option for desensitization and treatment of antibody-mediated rejection in kidney transplant candidates.