Practical guidelines for monitoring and management of coagulopathy following tisagenlecleucel CAR T-cell therapy.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
26 01 2021
26 01 2021
Historique:
received:
22
06
2020
accepted:
06
12
2020
entrez:
26
1
2021
pubmed:
27
1
2021
medline:
15
5
2021
Statut:
ppublish
Résumé
Cytokine release syndrome (CRS) is a systemic inflammatory response associated with chimeric antigen receptor T-cell (CAR-T) therapies. In severe cases, CRS can be associated with coagulopathy and hypofibrinogenemia. We present our global multicenter experience with CRS-associated coagulopathy after tisagenlecleucel therapy in 137 patients with relapsed or refractory B-cell acute lymphoblastic leukemia from the ELIANA and ENSIGN trials. These trials included clinical guidelines for fibrinogen replacement during CRS-associated coagulopathy. Hypofibrinogenemia requiring replacement was observed only in patients with severe CRS. A higher percentage of patients who required replacement were <10 years old, compared with those who did not require replacement. Twenty-three patients received replacement for hypofibrinogenemia (<1.5 g/L); 9 of them developed marked hypofibrinogenemia (<1 g/L). Very low fibrinogen levels (<1 g/L) were documented in patients before maximal CRS (n = 1), during maximal CRS (n = 7), and at CRS improvement (n = 1). Although hypofibrinogenemia was the most clinically significant coagulopathy, some patients also developed prolonged prothrombin time and activated partial thromboplastin time and increased international normalized ratio, further increasing the risk of bleeding. Hypofibrinogenemia was effectively managed using fibrinogen concentrate or cryoprecipitate replacement; severe (grade 4) bleeding events were rare (n = 2). CRS-associated coagulopathy with hypofibrinogenemia is manageable according to empiric guidelines of fibrinogen replacement for CAR-T trials. Fibrinogen concentrate should be used when cryoprecipitate is not reliably available. Monitoring fibrinogen levels in patients with moderate or severe CRS is essential for avoiding potentially fatal bleeding events. These trials were registered at www.clinicaltrials.gov as #NCT02435849 and #NCT02228096.
Identifiants
pubmed: 33496754
pii: S2473-9529(21)00076-8
doi: 10.1182/bloodadvances.2020002757
pmc: PMC7839371
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Receptors, Chimeric Antigen
0
tisagenlecleucel
Q6C9WHR03O
Banques de données
ClinicalTrials.gov
['NCT02435849', 'NCT02228096']
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
593-601Subventions
Organisme : NCI NIH HHS
ID : P01 CA214278
Pays : United States
Informations de copyright
© 2021 by The American Society of Hematology.
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