Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
13 10 2020
13 10 2020
Historique:
received:
19
05
2020
accepted:
12
08
2020
entrez:
9
10
2020
pubmed:
10
10
2020
medline:
15
5
2021
Statut:
ppublish
Résumé
ZUMA-1 demonstrated a high rate of durable response and a manageable safety profile with axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with refractory large B-cell lymphoma. As previously reported, prespecified clinical covariates for secondary end point analysis were not clearly predictive of efficacy; these included Eastern Cooperative Oncology Group performance status (0 vs 1), age, disease subtype, disease stage, and International Prognostic Index score. We interrogated covariates included in the statistical analysis plan and an extensive panel of biomarkers according to an expanded translational biomarker plan. Univariable and multivariable analyses indicated that rapid CAR T-cell expansion commensurate with pretreatment tumor burden (influenced by product T-cell fitness), the number of CD8 and CCR7+CD45RA+ T cells infused, and host systemic inflammation, were the most significant determining factors for durable response. Key parameters differentially associated with clinical efficacy and toxicities, with both theoretical and practical implications for optimizing CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT02348216.
Identifiants
pubmed: 33035333
pii: S2473-9529(20)31223-4
doi: 10.1182/bloodadvances.2020002394
pmc: PMC7556133
doi:
Substances chimiques
Antigens, CD19
0
Biological Products
0
axicabtagene ciloleucel
U2I8T43Y7R
Banques de données
ClinicalTrials.gov
['NCT02348216']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4898-4911Subventions
Organisme : NCI NIH HHS
ID : K23 CA201594
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR003167
Pays : United States
Informations de copyright
© 2020 by The American Society of Hematology.
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