Proteasome inhibitor treatment of antibody-mediated allograft rejection

Bortezomib is a first-in-class proteasome inhibitor that was originally Food and Drug Administration approved for the treatment of multiple myeloma. In the past few years, off-label use in solid organ transplant recipients has demonstrated its ability to provide plasma cell-targeted therapy in humans. The purpose of this review is to provide an update of recent basic science and clinical results with bortezomib in treating antibody-mediated rejection (AMR) that occurs in solid organ transplant recipients.

Proteasome inhibitor therapy for AMR in kidney transplant recipients is effective both as primary and as rescue therapy. Optimal responses with proteasome inhibitor therapy are obtained when AMR is diagnosed promptly and early in the posttransplant period. However, proteasome inhibitor therapy for late AMR (i.e., occurring 6 months or later posttransplant) provides less predictable results, likely due to the existence of a substantial bone marrow niche-resident long-lived plasma cell population. Proteasome inhibitor therapy has also recently been shown to provide effective therapy for AMR in heart, and also, transplant recipients.

Proteasome inhibitor therapy with bortezomib provides effective treatment for AMR in solid organ transplant recipients. As the first plasma cell-targeted therapy, proteasome inhibitor therapy provides the additional advantage of opening new possibilities for biologically defined plasma cell-targeted therapies.