Efficacy of bortezomib desensitization among heart transplant candidates

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.

Does bortezomib influence pre‐transplant desensitization therapy or benefit post‐heart transplant outcomes for highly sensitized patients?

“…These patients underwent selective crossing of C1q negative antigens and noted 1 year survival post-transplant to be 89% with 33% rate of AMR. 20 It remains uncertain whether the benefits of desensitization with PP/BTZ in patients awaiting heart transplantation outweigh potential risks (particularly if repeated cycles are administered), and thus further studies are clearly warranted. However, given that almost all of our study population was listed status 1 at transplant, any strategy which facilitates transplant in this high-risk group is likely of benefit.…”

“…presents 25 patients who underwent with plasma exchange, intravenous immunoglobulin, and bortezomib note a significant decrease in the median number of HLA class I but not class II antibodies. These patients underwent selective crossing of C1q negative antigens and noted 1 year survival post‐transplant to be 89% with 33% rate of AMR 20 …”