Efficacy of bortezomib desensitization among heart transplant candidates

Clin Transplant. 2023 Apr;37(4):e14907. doi: 10.1111/ctr.14907. Epub 2023 Feb 2.

Abstract

Allosensitization is prevalent in heart transplant candidates and is associated with prolonged waiting times and poor outcomes following transplantation. We analyzed the efficacy of a desensitization regimen consisting of plasma exchange, intravenous immunoglobulin, and bortezomib among 25 consecutive sensitized waitlisted candidates at our center from 2016 to 2021. Following desensitization therapies, all C1q negative antibodies were removed from a candidate's unacceptable antigen list. There was a significant decrease in the median number of human leukocyte antigen (HLA) class I (21-15, p = .001) but not class II antibodies (7-6.5, p = .07). There was a significant corresponding decrease in median calculated panel reactive antibodies for class I (90%-74%, p = .004) but not class II (74.5%-75.5%, p = .30). Following desensitization, 76% of patients were transplanted at a median of 91 days. One-year survival following transplant was 89% with a 33% rate of antibody-mediated rejection (AMR). In conclusion, a bortezomib desensitization protocol was modestly effective for class I antibodies and allowed successful transplant in most cases when combined with selective crossing of C1q negative antigens.

Keywords: alloantibody; antibody-mediated (ABMR); desensitization; immunosuppressant; other; rejection.

MeSH terms

  • Antibodies
  • Bortezomib / therapeutic use
  • Complement C1q*
  • Desensitization, Immunologic / methods
  • Graft Rejection / drug therapy
  • Graft Rejection / etiology
  • HLA Antigens
  • Heart Transplantation*
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Isoantibodies

Substances

  • Bortezomib
  • Complement C1q
  • Antibodies
  • Immunoglobulins, Intravenous
  • HLA Antigens
  • Isoantibodies