Metabolic profile evolution in relapsed/refractory B-cell non-Hodgkin lymphoma patients treated with CD19 chimeric antigen receptor T-cell therapy and implications in clinical outcome

作者：Serena De Matteis, Laura Del Coco, Federica De Castro, Anna Maria Giudetti, Beatrice Casadei, F Iannotta, Francesco De Felice, Enrica Tomassini, Francesca Vaglio, Maria Naddeo, Irene Salamon, Gianluca Storci, Noemi Laprovitera, Daria Messelodi, Salvatore Nicola Bertuccio, Marta Tassoni, Barbara Sinigaglia, Francesco Barbato, Margherita Ursi, Elena Campanini, Enrico Maffini, Marcello Roberto, Cinzia Pellegrini, Elisa Dan, Chiara Pirazzini, Paolo Garagnani, Manuela Ferracin, Pier Luigi Zinzani, Francesco Paolo Fanizzi, Massimiliano Bonafè, Francesca Bonifazi · 发表于：Haematologica · 年份：2024 · DOI：10.3324/haematol.2024.285154 · 被引用次数：4 · 研究领域：CAR-T cell therapy research、Immune Cell Function and Interaction、Viral Infectious Diseases and Gene Expression in Insects

Plasma metabolomics analysis was performed on 44 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r/BNHL) infused with approved CD19 chimeric antigen receptor (CAR) T-cell products at the time of pre-lymphodepletion (PLD) and at day +1 (D1), D7, and D30 after CAR T-cell infusion. At the PLD time point, a metabolic profile characterized by high lipoproteins and lactate and low glucose contributed to poor outcome prediction in association with high lactate dehydrogenase levels. At D1, higher plasma levels of lipid metabolism products and lower glucose and glycoproteins levels were observed in tisa-cel-compared to axi-cel-treated patients. At D30, discriminant analysis found two clusters in a subgroup of patients, one with complete response lasting 1 year after therapy, and another who relapsed within 1 year (relapsed >D30). This latter showed a higher content of N-GlycA, a known biomarker of systemic inflammation that is also correlated with C-reactive protein in our case setting of relapsing patients. Our data show complex metabolomic changes that track the evolution of the disease and drug activity in the first 30 days of CAR T-cell therapy. Conceivably, a pro-inflammatory drift may be linked to a forthcoming disease relapse in CAR T patients.