Complement as the enabler of carfilzomib-induced thrombotic microangiopathy.
Adult
Aged
Antibodies, Monoclonal, Humanized
/ administration & dosage
Complement Membrane Attack Complex
/ adverse effects
Complement System Proteins
/ drug effects
Endothelial Cells
/ immunology
Female
Humans
Male
Middle Aged
Multiple Myeloma
/ complications
Oligopeptides
/ adverse effects
Prospective Studies
Proteasome Inhibitors
/ adverse effects
Thrombotic Microangiopathies
/ chemically induced
Ubiquitin
/ antagonists & inhibitors
C5b-9 deposits
carfilzomib
drug-induced thrombotic microangiopathy
eculizumab
endothelial cells
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
16
03
2020
accepted:
05
05
2020
pubmed:
30
5
2020
medline:
31
7
2021
entrez:
30
5
2020
Statut:
ppublish
Résumé
Carfilzomib has been associated with the development of thrombotic microangiopathy (TMA) in relapsed/refractory multiple myeloma patients, a severe disease with no currently available aetiological treatment. We evaluated the potential role of terminal complement pathway in four patients with carfilzomib-induced TMA. Membrane attack complex (C5b-9) deposition on endothelial cells in culture exposed to plasma from patients during the acute phase of the disease suggests complement overactivation as a mechanism of potential endothelial damage in three out of four patients. If confirmed in larger cohorts, C5b-9 evaluation will allow early identification of patients who could benefit from complement blockade and treatment monitoring.
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Complement Membrane Attack Complex
0
Oligopeptides
0
Proteasome Inhibitors
0
Ubiquitin
0
carfilzomib
72X6E3J5AR
Complement System Proteins
9007-36-7
eculizumab
A3ULP0F556
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
181-187Subventions
Organisme : Spanish Kidney Research Network (ISCIII-RETIC REDinREN)
ID : RD16/0009/0023
Organisme : CERCA Program of the Generalitat de Catalunya
Organisme : Instituto de Salud Carlos III/ Fondo Europeo de Desarrollo Regional (ISCIII/FEDER)
ID : PI19/00669
Organisme : Instituto de Salud Carlos III/ Fondo Europeo de Desarrollo Regional (ISCIII/FEDER)
ID : PI19/00888
Organisme : Fundació Miarnau
Organisme : Jazz Pharmaceuticals Plc
ID : IST-16-10355
Organisme : German José Carreras Leukaemia Foundation
ID : 03R/2019
Organisme : Instituto de Salud Carlos III / Fondo Europeo de Desarrollo Regional (ISCIII/FEDER)
ID : PI19/00669
Organisme : Instituto de Salud Carlos III / Fondo Europeo de Desarrollo Regional (ISCIII/FEDER)
ID : PI19/00888
Informations de copyright
© 2020 British Society for Haematology and John Wiley & Sons Ltd.
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