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TOPLINE:

Gut microbiome analysis of patients with multiple myeloma receiving idecabtagene vicleucel (ide-cel) therapy revealed specific bacterial species linked to treatment response and toxicity outcomes. Major microbiome disruption, defined by dominant taxa prevalence > 35%, correlated with higher cytokine release syndrome risk.

METHODOLOGY:

• Researchers conducted whole-genome shotgun sequencing on 117 stool samples collected from 33 patients with multiple myeloma undergoing ide-cel therapy at The University of Texas MD Anderson Cancer Center (n = 20) and Moffitt Cancer Center (n = 13) between September 2021 and July 2022.
• Sample collection spanned from 49 days before to 91 days after ide-cel infusion, with timepoints categorized as: Apheresis (median, day −21), pre-lymphodepletion (median, day −5), at ide-cel infusion (median, day 0), 1 week post–ide-cel (median, day +7), and ≥ 2 weeks post–ide-cel (median, day +28).
• Analysis included mass spectrometric assessment of stool metabolites, including short-chain fatty acids, indoles, and anionic metabolites from samples collected on the day of ide-cel infusion (n = 16).

TAKEAWAY:

• Patients with genus dominance in baseline samples showed significantly higher incidence of grade ≥ 2 cytokine release syndrome at 46.2% compared with 11.1% in those without genus dominance (P = .043).
• Researchers identified enrichment of specific bacterial species in responders, including Flavonifractor plautii, Bacteroides thetaiotaomicron, Blautia faecis, and Dysosmobacter species, with these bacteria showing significant correlation with elevated short-chain fatty acid levels.
• According to the authors, bacterial diversity decreased significantly post–ide-cel infusion, with notable changes in bacterial composition linked to therapy response and toxicities.
• Network analysis revealed F plautii was associated with increased indole metabolites in responders, suggesting potential mechanistic pathways affecting treatment outcomes.

IN PRACTICE:

“Our findings uncover novel microbiome associations between ide-cel responses and toxicities that may be useful for developing modalities to improve CAR T outcomes....Exploring these avenues could lead to the identification of specific microbiome modifications that enhance CAR T-cell efficacy or reduce toxicity,” the authors of the study wrote.

SOURCE:

This study was led by Neeraj Saini, The University of Texas MD Anderson Cancer Center in Houston. It was published online in Blood Advances.

LIMITATIONS:

According to the authors, the discrepancy in bacterial species associated with responses between this study and previous research could be attributed to the smaller cohort sizes and geographical differences between studies. The researchers noted that geographic region can significantly influence the predictive capability of microbiome models.

DISCLOSURES:

This study was supported by philanthropic contributions to The University of Texas MD Anderson Cancer Center Moon Shots Program and the Platform for Innovative Microbiome and Translational Research, as well as by Cancer Center Support Grants from the National Cancer Institute to MD Anderson Cancer Center and Moffitt Cancer Center. Neeraj Saini reported having ties with Panbela Therapeutics. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.