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
PMCID: PMC9434490
DOI/URL:
Notes: MSK author Pamela Hatfield's last name is listed as "Herrera" in this Publication -- Erratum published at DOI: 10.1038/s41591-022-02069-7 -- Source: Scopus
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MSK Authors
  1. Renier J Brentjens
    286 Brentjens
  2. Maria Lia Palomba
    415 Palomba
  3. Sergio Andres Giralt
    1053 Giralt
  4. Jae Hong Park
    356 Park
  5. Miguel-Angel Perales
    915 Perales
  6. Elizabeth F Halton
    53 Halton
  7. Michel W J Sadelain
    583 Sadelain
  8. Isabelle C Riviere
    240 Riviere
  9. Justin Robert Cross
    111 Cross
  10. Ying Taur
    147 Taur
  11. Sean McCarthy Devlin
    601 Devlin
  12. Melody Smith
    33 Smith
  13. Jonathan U Peled
    155 Peled
  14. Emily Fontana
    31 Fontana
  15. Aishat Olaide Afuye
    16 Afuye
  16. Antonio LC Gomes
    47 Gomes
  17. Annelie G Clurman
    27 Clurman
  18. Josel Dumo Ruiz
    54 Ruiz
  19. Gabriel Armijo
    17 Armijo
  20. Anqi Dai
    26 Dai
  21. Emmanuel Ampomah Dwomoh
    4 Dwomoh