title: Durability of antibody removal following proteasome inhibitor-based therapy.
abstract: 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 × 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.
authors.affiliation: One Lambda Inc., Research 2 Division, Los Angeles, CA 90064, USA. meverly@onelambda.com
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Everly
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
authors.forename: Hargovind L
authors.initials: HL
authors.lastname: Trivedi
mesh_terms: D000328:Adult; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D065095:Calcineurin Inhibitors; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011379:Prognosis; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use*; D012189:Retrospective Studies; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D001897:Boronic Acids; D065095:Calcineurin Inhibitors; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D009173:Mycophenolic Acid