Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy Journal Article

Authors: Smith, M.; Dai, A.; Ghilardi, G.; Amelsberg, K. V.; Devlin, S. M.; Pajarillo, R.; Slingerland, J. B.; Beghi, S.; Herrera, P. S.; Giardina, P.; Clurman, A.; Dwomoh, E.; Armijo, G.; Gomes, A. L. C.; Littmann, E. R.; Schluter, J.; Fontana, E.; Taur, Y.; Park, J. H.; Palomba, M. L.; Halton, E.; Ruiz, J.; Jain, T.; Pennisi, M.; Afuye, A. O.; Perales, M. A.; Freyer, C. W.; Garfall, A.; Gier, S.; Nasta, S.; Landsburg, D.; Gerson, J.; Svoboda, J.; Cross, J.; Chong, E. A.; Giralt, S.; Gill, S. I.; Riviere, I.; Porter, D. L.; Schuster, S. J.; Sadelain, M.; Frey, N.; Brentjens, R. J.; June, C. H.; Pamer, E. G.; Peled, J. U.; Facciabene, A.; van den Brink, M. R. M.; Ruella, M.
Article Title: Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy
Abstract: 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. © 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
Keywords: retrospective studies; clinical trial; prospective study; prospective studies; retrospective study; multicenter study; intestine flora; adoptive immunotherapy; immunotherapy, adoptive; cd19 antigen; antigens, cd19; adverse event; neurotoxicity syndromes; humans; human; gastrointestinal microbiome; receptors, chimeric antigen; toxicity and intoxication
Journal Title: Nature Medicine
Volume: 28
Issue: 4
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 2022-04-01
Start Page: 713
End Page: 723
Language: English
DOI: 10.1038/s41591-022-01702-9
PUBMED: 35288695
PROVIDER: scopus
Notes: Article -- Export Date: 1 June 2022 -- Source: Scopus
Citation Impact
MSK Authors
  1. Renier J Brentjens
    274 Brentjens
  2. Maria Lia Palomba
    248 Palomba
  3. Sergio Andres Giralt
    792 Giralt
  4. Jae Hong Park
    237 Park
  5. Miguel-Angel Perales
    626 Perales
  6. Elizabeth F Halton
    50 Halton
  7. Michel W J Sadelain
    531 Sadelain
  8. Isabelle C Riviere
    216 Riviere
  9. Justin Robert Cross
    81 Cross
  10. Ying Taur
    131 Taur
  11. Sean McCarthy Devlin
    463 Devlin
  12. Melody Smith
    29 Smith
  13. Jonathan U Peled
    100 Peled
  14. Emily Fontana
    24 Fontana
  15. Aishat Olaide Afuye
    14 Afuye
  16. Antonio LC Gomes
    39 Gomes
  17. Annelie G Clurman
    20 Clurman
  18. Josel Dumo Ruiz
    43 Ruiz
  19. Gabriel Armijo
    8 Armijo
  20. Anqi Dai
    8 Dai
  21. Emmanuel Ampomah Dwomoh
    2 Dwomoh