Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma.
CART
NEOPLASIA/lymphomas and other lymphoproliferative conditions
corticosteroid
lymphoma
outcome
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
10 06 2021
10 06 2021
Historique:
received:
08
09
2020
accepted:
12
01
2021
pubmed:
4
2
2021
medline:
15
12
2021
entrez:
3
2
2021
Statut:
ppublish
Résumé
Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy-associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy-associated toxicities.
Identifiants
pubmed: 33534891
pii: S0006-4971(21)00237-8
doi: 10.1182/blood.2020008865
pmc: PMC8351896
doi:
Substances chimiques
Adrenal Cortex Hormones
0
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3272-3276Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Informations de copyright
© 2021 by The American Society of Hematology.
Références
Nat Med. 2020 Dec;26(12):1878-1887
pubmed: 33020644
Lancet. 2020 Sep 19;396(10254):839-852
pubmed: 32888407
J Clin Oncol. 2020 Sep 20;38(27):3119-3128
pubmed: 32401634
J Clin Oncol. 2014 Sep 20;32(27):3059-68
pubmed: 25113753
Lancet Oncol. 2019 Jan;20(1):31-42
pubmed: 30518502
Blood. 2017 Nov 23;130(21):2295-2306
pubmed: 28924019
Sci Transl Med. 2016 Sep 7;8(355):355ra116
pubmed: 27605551
N Engl J Med. 2019 Jan 3;380(1):45-56
pubmed: 30501490
Clin Exp Immunol. 1996 Mar;103(3):482-90
pubmed: 8608650
Cancer Immunol Res. 2015 May;3(5):473-82
pubmed: 25711538
Blood Adv. 2020 Aug 25;4(16):3943-3951
pubmed: 32822484
Regul Pept. 1998 Jan 2;73(1):59-65
pubmed: 9537674
Blood Adv. 2020 Oct 13;4(19):4898-4911
pubmed: 33035333
Nat Rev Clin Oncol. 2018 Jan;15(1):47-62
pubmed: 28925994
Blood Adv. 2020 Jul 14;4(13):3123-3127
pubmed: 32645136
J Clin Oncol. 2020 Sep 20;38(27):3095-3106
pubmed: 32667831
J Immunol. 1993 Oct 15;151(8):4081-9
pubmed: 8409387
Cancer Discov. 2018 Aug;8(8):958-971
pubmed: 29880584
J Clin Oncol. 2017 Jun 1;35(16):1803-1813
pubmed: 28291388
N Engl J Med. 2017 Dec 28;377(26):2531-2544
pubmed: 29226797