Bortezomib as the Sole Post‐Renal Transplantation Desensitization Agent Does Not Decrease Donor‐Specific Anti‐HLA Antibodies

Abstract

Persistence of donor-specific anti-HLA antibodies (DSA) associated with antibody-mediated graft injuries following kidney transplantation predicts evolution toward chronic humoral rejection and reduced graft survival. Targeting plasma cells, the main antibodyproducing cells, with the proteasome inhibitor bortezomib may be a promising desensitization strategy. We evaluated the in vivo efficacy of one cycle of bortezomib (1.3 mg/m 2 × 4 doses), used as the sole desensitization therapy, in four renal transplant recipients experiencing subacute antibody-mediated rejection with persisting DSA (>2000 [Mean Fluorescence Intensity] MFI). Bortezomib treatment did not significantly decrease DSA MFI within the 150-day posttreatment period in any patient. In addition, antivirus (HBV, VZV and HSV) antibody levels remained stable following treatment suggesting a lack of efficacy on long-lived plasma cells. In conclusion, one cycle of bortezomib alone does not decrease DSA levels in sensitized kidney transplant recipients in the time period studied. These results underscore the need to evaluate this new desensitization agent properly in prospective, randomized and well-controlled studies.

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation

“…However, one study found that bortezomib alone did not decrease DSA levels [18]. These results are conflicting, and it remains unclear if bortezomib used in combination therapy really leads to a significant decrease in DSAs [19,20].…”

“…There are conflicting reports on whether additional therapy with the proteasome inhibitor bortezomib provides a further beneficial effect [19]. However, bortezomib alone was not effective in treating CAMR [20].…”

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“…14 In vitro, bortezomib induces apoptosis of all antibody-producing plasma cells. 15 In the absence of rituximab-induced complete remission despite near eradication of a CD20-positive cell count, bortezomib was introduced. Within 2 months, considerable drops in CD34-positive and CD138-positive cell counts were noted in our patient, which was paralleled by a significant reduction in proteinuria that disappeared several months later (Figure 3).…”

Induction Immunosuppressive Therapy in Kidney Transplantation

“…Further study of bortezomib is justified in prospective, randomized controlled studies because steroids and proteasome inhibitors such as bortezomib may act synergistically to target plasma cells, and a combination of these 2 drugs may be beneficial. 26 …”