Thrombotic microangiopathy in untreated myeloma patients receiving carfilzomib, cyclophosphamide and dexamethasone on the CARDAMON study.
Acute Kidney Injury
/ drug therapy
Aged
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Cyclophosphamide
/ administration & dosage
Dexamethasone
/ administration & dosage
Female
Humans
Male
Middle Aged
Multiple Myeloma
/ drug therapy
Oligopeptides
/ administration & dosage
Thrombotic Microangiopathies
/ chemically induced
carfilzomib
clinical trials
myeloma
thrombocytopenia
thrombotic haemolytic anaemias
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
24
12
2020
accepted:
02
02
2021
pubmed:
3
3
2021
medline:
29
9
2021
entrez:
2
3
2021
Statut:
ppublish
Résumé
Proteasome inhibitors have been associated with thrombotic microangiopathy (TMA) - a group of disorders characterised by occlusive microvascular thrombosis causing microangiopathic haemolytic anaemia, thrombocytopenia and end-organ damage. To date, carfilzomib-associated TMA has predominantly been described in relapsed/refractory myeloma patients. We report eight patients with newly diagnosed myeloma who experienced TMA events while receiving carfilzomib on the phase II CARDAMON trial. The first three occurred during maintenance single-agent carfilzomib, two occurred at induction with carfilzomib given with cyclophosphamide and dexamethasone (KCd) and three occurred during KCd consolidation. At TMA presentation 6/8 were hypertensive; 7/8 had acute kidney injury and in three, renal impairment persisted after resolution of TMA in other respects. The mechanism of carfilzomib-associated TMA remains unclear, though patients with known hypertension seem particularly susceptible. Given the first three cases occurred during maintenance after a longer than five-week treatment break, a protocol amendment was instituted with: aggressive hypertension management, carfilzomib step-up dosing (20 mg/m
Substances chimiques
Oligopeptides
0
carfilzomib
72X6E3J5AR
Dexamethasone
7S5I7G3JQL
Cyclophosphamide
8N3DW7272P
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
750-760Subventions
Organisme : Medical Research Council
ID : MC_UU_00025/10
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C9203/A17750
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
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