Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
08
04
2021
accepted:
13
01
2022
pubmed:
16
3
2022
medline:
22
4
2022
entrez:
15
3
2022
Statut:
ppublish
Résumé
Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has led to unprecedented responses in patients with high-risk hematologic malignancies. However, up to 60% of patients still experience disease relapse and up to 80% of patients experience CAR-mediated toxicities, such as cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. We investigated the role of the intestinal microbiome on these outcomes in a multicenter study of patients with B cell lymphoma and leukemia. We found in a retrospective cohort (n = 228) that exposure to antibiotics, in particular piperacillin/tazobactam, meropenem and imipenem/cilastatin (P-I-M), in the 4 weeks before therapy was associated with worse survival and increased neurotoxicity. In stool samples from a prospective cohort of CAR T cell recipients (n = 48), the fecal microbiome was altered at baseline compared to healthy controls. Stool sample profiling by 16S ribosomal RNA and metagenomic shotgun sequencing revealed that clinical outcomes were associated with differences in specific bacterial taxa and metabolic pathways. Through both untargeted and hypothesis-driven analysis of 16S sequencing data, we identified species within the class Clostridia that were associated with day 100 complete response. We concluded that changes in the intestinal microbiome are associated with clinical outcomes after anti-CD19 CAR T cell therapy in patients with B cell malignancies.
Identifiants
pubmed: 35288695
doi: 10.1038/s41591-022-01702-9
pii: 10.1038/s41591-022-01702-9
pmc: PMC9434490
mid: NIHMS1816622
doi:
Substances chimiques
Antigens, CD19
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
713-723Subventions
Organisme : NCI NIH HHS
ID : R01 CA226983
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA214278
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA023766
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147584
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA219871
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA262362
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL125571
Pays : United States
Organisme : NCI NIH HHS
ID : K99 CA212302
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228358
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA212302
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL143189
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL123340
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA206012
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228308
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG052359
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
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