Longitudinal Analysis of Gut Microbiome and Metabolome Correlates of Response and Toxicity With Idecabtagene Vicleucel

Authors

Satabdi Saha
Lubna Rehman
Abdur Rehman
Faezeh Darbaniyan
Donna M Weber
Melody Becnel
Mahmoud Gaballa
Sheeba K Thomas
Hans C Lee
Chia-Chi Chang
Reetakshi Arora
Meghan Menges
Salvatore Corallo
Marco L Davila
Frederick L Locke
Mark R Tanner
Sattva S Neelapu
Elizabeth J Shpall
Christopher R Flowers
Robert Z Orlowski
Robert R Jenq
Michael D Jain
Christine Peterson
Doris K Hansen
Neeraj Y Saini
Krina K Patel

Publication Date

7-22-2025

Journal

Blood Advances

DOI

10.1182/bloodadvances.2024014476

PMID

40198765

PMCID

PMC12274813

PubMedCentral® Posted Date

4-10-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Increasing evidence suggests that the gut microbiome may influence the responses and toxicities associated with chimeric antigen receptor T-cell (CAR-T) therapy. We conducted whole-genome shotgun sequencing on stool samples (N = 117) collected at various times from patients with multiple myeloma (n = 33) who underwent idecabtagene vicleucel (ide-cel) anti-B-cell maturation antigen CAR-T therapy. We observed a significant decrease in bacterial diversity after ide-cel infusion, along with significant differences in the bacterial composition linked to therapy response and toxicities. Specifically, we found significant enrichment of Flavonifractor plautii, Bacteroides thetaiotaomicron, Blautia fecis, and Dysosmobacter species in ide-cel responders. A notable finding was the link of major microbiome disruption, defined as the presence of dominant specific taxa (>35% prevalence), and increased facultative pathobionts, like Enterococcus, with ide-cel toxicities, especially cytokine release syndrome (CRS). Patients with genus dominance in baseline samples had a higher incidence of grade 2 or higher CRS at 46.2% than those without genus dominance (11.1%; P = .043). In addition, network analysis and mass spectrometric assessment of stool metabolites revealed important associations and pathways, such as F plautii being linked to increased indole metabolites and pathways in responders. Our findings uncovered novel microbiome associations between ide-cel responses and toxicities that may be useful for developing modalities to improve CAR-T outcomes.

Keywords

Humans, Gastrointestinal Microbiome, Metabolome, Immunotherapy, Adoptive, Male, Female, Middle Aged, Aged, Longitudinal Studies, Feces, Receptors, Chimeric Antigen

Published Open-Access

yes

Recommended Citation

Saha, Satabdi; Rehman, Lubna; Rehman, Abdur; et al., "Longitudinal Analysis of Gut Microbiome and Metabolome Correlates of Response and Toxicity With Idecabtagene Vicleucel" (2025). Faculty, Staff and Student Publications. 4901.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4901