A polyamine-centric, blood-based metabolite panel predictive of poor response to CAR-T cell therapy in large B cell lymphoma

Fahrmann, Johannes F.; Saini, Neeraj; Chang, Chen; Irajizad, Ehsan; Nair, Ranjit; Fayad, Luis; Ahmed, Sairah; Lee, Hun Ju; Iyer, Swaminathan Padmanabhan; Steiner, Raphaël; Vykoukal, Jody; Wu, Ranran; Dennison, Jennifer B.; Nastoupil, Loretta J.; Jain, Preetesh; Wang, Michael; Green, Michael; Westin, Jason R.; Blumenberg, Viktoria; Davila, Marco L.; Champlin, Richard E.; Shpall, Elizabeth J.; Kebriaei, Partow; Flowers, Christopher R.; Jain, Michael D.; Jenq, Robert R.; Stein‐Thoeringer, Christoph K.; Subklewe, Marion; Neelapu, Sattva S.; Hanash, Sam

doi:10.1016/j.xcrm.2022.100720

Cited by 5 publications

(1 citation statement)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therapy monitoring, and in particular, next-generation immunotherapies like checkpoint inhibitors, bispecific immunomodulatory antibodies and chimeric antigen receptor T-cell therapy (CAR-T), pose challenges regarding the identification of meaningful biomarkers for patient selection and follow-up of treatment regimes. In this context, liquid biopsy-based approaches can rapidly provide useful information for clinical decisions (11)(12)(13).…”

Section: Liquid Biopsies In Hematological Malignanciesmentioning

confidence: 99%

Editorial: Liquid biopsies in hematological malignancies

García-Silva,

Marchetti,

Gallardo

2024

Front. Immunol.

View full text Add to dashboard Cite

Section: Liquid Biopsies In Hematological Malignanciesmentioning

confidence: 99%

Editorial: Liquid biopsies in hematological malignancies

García-Silva,

Marchetti,

Gallardo

2024

Front. Immunol.

View full text Add to dashboard Cite

Biomarkers of outcome in patients undergoing CD19 CAR‐T therapy for large B cell lymphoma

Gong,

Tran,

Saibil

et al. 2024

HemaSphere

View full text Add to dashboard Cite

CD19‐directed autologous chimeric antigen receptor T cell (CAR‐T) therapy has transformed the management of relapsed/refractory (R/R) large B cell lymphoma (LBCL). Initially approved in the third line and beyond setting, CAR‐T is now standard of care (SOC) for second‐line treatment in patients with refractory disease or early relapse (progression within 12 months) following primary chemoimmunotherapy. Despite becoming SOC, most patients do not achieve complete response, and long‐term cure is only observed in approximately 40% of patients. Accordingly, there is an urgent need to better understand the mechanisms of treatment failure and to identify patients that are unlikely to benefit from SOC CAR‐T. The field needs robust biomarkers to predict treatment outcome, as better understanding of prognostic factors and mechanisms of resistance can inform on the design of novel treatment approaches for patients predicted to respond poorly to SOC CAR‐T. This review aims to provide a comprehensive overview of clinical, molecular, imaging, and cellular features that have been shown to influence outcomes of CAR‐T therapy in patients with R/R LBCL.

show abstract

Multi-omics signatures in new-onset diabetes predict metabolic response to dietary inulin: findings from an observational study followed by an interventional trial

et al. 2023

View full text Add to dashboard Cite

Aim The metabolic performance of the gut microbiota contributes to the onset of type 2 diabetes. However, targeted dietary interventions are limited by the highly variable inter-individual response. We hypothesized (1) that the composition of the complex gut microbiome and metabolome (MIME) differ across metabolic spectra (lean-obese-diabetes); (2) that specific MIME patterns could explain the differential responses to dietary inulin; and (3) that the response can be predicted based on baseline MIME signature and clinical characteristics. Method Forty-nine patients with newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 healthy lean (LH) volunteers were compared in a cross-sectional case-control study integrating clinical variables, dietary intake, gut microbiome, and fecal/serum metabolomes (16 S rRNA sequencing, metabolomics profiling). Subsequently, 27 DM were recruited for a predictive study: 3 months of dietary inulin (10 g/day) intervention. Results MIME composition was different between groups. While the DM and LH groups represented opposite poles of the abundance spectrum, OB was closer to DM. Inulin supplementation was associated with an overall improvement in glycemic indices, though the response was very variable, with a shift in microbiome composition toward a more favorable profile and increased serum butyric and propionic acid concentrations. The improved glycemic outcomes of inulin treatment were dependent on better baseline glycemic status and variables related to the gut microbiota, including the abundance of certain bacterial taxa (i.e., Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, or Phascolarctobacterium), serum concentrations of branched-chain amino acid derivatives and asparagine, and fecal concentrations of indole and several other volatile organic compounds. Conclusion We demonstrated that obesity is a stronger determinant of different MIME patterns than impaired glucose metabolism. The large inter-individual variability in the metabolic effects of dietary inulin was explained by differences in baseline glycemic status and MIME signatures. These could be further validated to personalize nutritional interventions in patients with newly diagnosed diabetes.

show abstract

A polyamine-centric, blood-based metabolite panel predictive of poor response to CAR-T cell therapy in large B cell lymphoma

Cited by 5 publications

References 52 publications

Editorial: Liquid biopsies in hematological malignancies

Editorial: Liquid biopsies in hematological malignancies

Biomarkers of outcome in patients undergoing CD19 CAR‐T therapy for large B cell lymphoma

Multi-omics signatures in new-onset diabetes predict metabolic response to dietary inulin: findings from an observational study followed by an interventional trial

Contact Info

Product

Resources

About