Impact of carfilzomib-based desensitization on heart transplantation of sensitized candidates.
C1q
cPRA
carfilzomib
desensitization
heart transplant
Journal
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
ISSN: 1557-3117
Titre abrégé: J Heart Lung Transplant
Pays: United States
ID NLM: 9102703
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
10
10
2020
revised:
14
02
2021
accepted:
02
03
2021
pubmed:
1
4
2021
medline:
1
2
2022
entrez:
31
3
2021
Statut:
ppublish
Résumé
Allosensitization in heart transplant candidates is associated with longer transplant wait times and post-transplant complications. We summarize our experience with desensitization using carfilzomib, an irreversible proteasome inhibitor that causes plasma cell apoptosis. One cycle of desensitization consisted of plasmapheresis and carfilzomib 20 mg/m From June 2013 to October 2019, 9 patients underwent 20 cycles of carfilzomib-based desensitization. Each cycle resulted in an average cPRA decrease of 24% (95% CI: 6-42) for IgG and 36% (95% CI: 17-55) for C1q. From treatment start to finish, mean cPRA fell from 76% to 40% (p = 0.01) for IgG and 56% to 4% (p = 0.017) for C1q. Six of 9 patients have been transplanted with 5 of the transplanted hearts crossing preoperative donor-specific antibodies. During a median follow-up of 35.1 months, all transplanted patients have survived with only 1 occurrence of treated rejection. Side effects of desensitization included acute kidney injury (67%) and thrombocytopenia (33%) with all episodes self-resolving. A carfilzomib-based desensitization strategy among heart transplant candidates reduces the level of HLA antibodies and complement binding, facilitates successful transplantation, and is associated with excellent outcomes at 3 years.
Sections du résumé
BACKGROUND
Allosensitization in heart transplant candidates is associated with longer transplant wait times and post-transplant complications. We summarize our experience with desensitization using carfilzomib, an irreversible proteasome inhibitor that causes plasma cell apoptosis.
METHODS
One cycle of desensitization consisted of plasmapheresis and carfilzomib 20 mg/m
RESULTS
From June 2013 to October 2019, 9 patients underwent 20 cycles of carfilzomib-based desensitization. Each cycle resulted in an average cPRA decrease of 24% (95% CI: 6-42) for IgG and 36% (95% CI: 17-55) for C1q. From treatment start to finish, mean cPRA fell from 76% to 40% (p = 0.01) for IgG and 56% to 4% (p = 0.017) for C1q. Six of 9 patients have been transplanted with 5 of the transplanted hearts crossing preoperative donor-specific antibodies. During a median follow-up of 35.1 months, all transplanted patients have survived with only 1 occurrence of treated rejection. Side effects of desensitization included acute kidney injury (67%) and thrombocytopenia (33%) with all episodes self-resolving.
CONCLUSIONS
A carfilzomib-based desensitization strategy among heart transplant candidates reduces the level of HLA antibodies and complement binding, facilitates successful transplantation, and is associated with excellent outcomes at 3 years.
Identifiants
pubmed: 33785250
pii: S1053-2498(21)02218-X
doi: 10.1016/j.healun.2021.03.001
pii:
doi:
Substances chimiques
Oligopeptides
0
carfilzomib
72X6E3J5AR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
595-603Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure statement The authors have no conflicts of interest to disclose.