32 Doses of Bortezomib for Desensitization Is Not Well Tolerated and Is Associated With Only Modest Reductions in Anti-HLA Antibody

Transplantation. 2017 Jun;101(6):1222-1227. doi: 10.1097/TP.0000000000001330.

Abstract

Background: We previously showed that bortezomib (BTZ) partially depletes plasma cells, yet has limited efficacy for desensitization in kidney transplant candidates when up to 16 doses is given.

Methods: This study aimed to determine the safety and efficacy of 32 doses of BTZ (1.3 mg/m of body surface area) in 10 highly sensitized kidney transplant candidates with alloantibodies against their intended living donor.

Results: Dose reduction was needed in 2 patients and 2 others completely discontinued therapy for adverse events. Anti-HLA antibodies mean fluorescence intensity (MFI) values were stable prior to BTZ (P = 0.96) but decreased after therapy (mean decrease of 1916 [SE, 425] MFI, P < 0.01). No patient developed a negative crossmatch against their original intended donor, and the calculated panel-reactive antibodies based on MFI of 2000, 4000, and 8000 was unchanged in all patients.

Conclusions: These data suggest that 32 doses of BTZ monotherapy was not well tolerated and resulted in only a modest reduction in anti-HLA antibodies.

Trial registration: ClinicalTrials.gov NCT00722722.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers / blood
  • Bortezomib / administration & dosage*
  • Bortezomib / adverse effects
  • Desensitization, Immunologic / methods*
  • Down-Regulation
  • Drug Administration Schedule
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • HLA Antigens / immunology*
  • Histocompatibility Testing
  • Histocompatibility*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Isoantibodies / blood*
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Living Donors
  • Male
  • Middle Aged
  • Minnesota
  • Prospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • HLA Antigens
  • Immunosuppressive Agents
  • Isoantibodies
  • Bortezomib

Associated data

  • ClinicalTrials.gov/NCT00722722