Risk stratification of patients with diffuse large B-cell lymphoma using plasma NMR-based metabolomics at diagnosis

作者：Aurélie Montagne, Gildas Bertho, Θωμάς Παπαστεργίου, Loïc Chartier, Romain Ricci, Fabrice Jardin, Hervé Ghesquières, Cédric Rossi, Franck Morschhauser, Corinne Haïoun, Vincent Ribrag, Pierre Feugier, Gabriel Brisou, Lucie Obéric, Philippe Gaulard, Nicolas Giraud, Younès Bennani, Catherine Thieblemont, Véronique Baud · 发表于：Blood Advances · 年份：2025 · DOI：10.1182/bloodadvances.2025017248 · 被引用次数：2 · 研究领域：Metabolomics and Mass Spectrometry Studies

ABSTRACT: Early detection of ultrahigh-risk diffuse large B-cell lymphoma (DLBCL) is an unmet medical need to aid patient stratification for alternative treatment approaches. Metabolomics applied to biofluids of patients with cancer has emerged as a novel omics that could provide important information to better stratify these patients. In this work, the authors performed a retrospective study by nuclear magnetic resonance (NMR)-based metabolomics using plasma samples at diagnosis from 154 randomized patients with DLBCL treated by R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) (from the phase 3 REMARC [Reduced-intensity Maintenance therapy with Rituximab After R-CHOP in elderly patients with DLBCL] trial). Remarkably, a combination of 3 circulating metabolites was linked to lipid metabolism (named the "NMR score") that significantly affected overall survival (OS) (P< .0001) and progression-free survival (PFS) (P = .0003). The optimal cutoff for each metabolite was determined using X-Tile and confirmed by a training validation method. Combining 2-amino-butyrate, 3-hydroxy-butyrate, and LDL-1 lipoprotein yielded 3 risk groups with low- (0-1), intermediate- (2-3), and high-risk (4-5) patients. Germinal center B-cell (GCB)/non-GCB profile along with Bcl2 and Myc expression did not correlate with NMR score survival. In conclusion, the combination of 3 circulating metabolites linked to lipid metabolism is revealed as a feature that captures heterogene...