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
Plasma metabolomics analysis was performed on 44 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r/B-NHL) infused with approved CD19.CAR-T cell products at the time of pre-lymphodepletion (PLD) and at day +1, +7, and +30 after CAR-T cell infusion. At the PLD time point, a metabolic...
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Ferrata Storti Foundation
2024-12-01
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| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/11875 |
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| author | Serena De Matteis Laura Del Coco Federica De Castro Anna Maria Giudetti Beatrice Casadei Francesco 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 |
| author_facet | Serena De Matteis Laura Del Coco Federica De Castro Anna Maria Giudetti Beatrice Casadei Francesco 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 |
| author_sort | Serena De Matteis |
| collection | DOAJ |
| description |
Plasma metabolomics analysis was performed on 44 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r/B-NHL) infused with approved CD19.CAR-T cell products at the time of pre-lymphodepletion (PLD) and at day +1, +7, and +30 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 day+1, 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 day+30, discriminant analysis found two clusters in a subgroup of patients, one with CR lasting one year after therapy, and another who relapsed within one 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.
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| format | Article |
| id | doaj-art-0467f20d229a43a5bf280ceb3ce6c1f0 |
| institution | OA Journals |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Ferrata Storti Foundation |
| record_format | Article |
| series | Haematologica |
| spelling | doaj-art-0467f20d229a43a5bf280ceb3ce6c1f02025-08-20T02:34:47ZengFerrata Storti FoundationHaematologica0390-60781592-87212024-12-01999110.3324/haematol.2024.285154Metabolic profile evolution in relapsed/refractory B-cell non-Hodgkin lymphoma patients treated with CD19 chimeric antigen receptor T-cell therapy and implications in clinical outcomeSerena De Matteis0Laura Del Coco1Federica De Castro2Anna Maria Giudetti3Beatrice Casadei4Francesco Iannotta5Francesco De Felice6Enrica Tomassini7Francesca Vaglio8Maria Naddeo9Irene Salamon10Gianluca Storci11Noemi Laprovitera12Daria Messelodi13Salvatore Nicola Bertuccio14Marta Tassoni15Barbara Sinigaglia16Francesco Barbato17Margherita Ursi18Elena Campanini19Enrico Maffini20Marcello Roberto21Cinzia Pellegrini22Elisa Dan23Chiara Pirazzini24Paolo Garagnani25Manuela Ferracin26Pier Luigi Zinzani27Francesco Paolo Fanizzi28Massimiliano Bonafè29Francesca Bonifazi30IRCCS Azienda Ospedaliero-Universitaria di BolognaDepartment of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, LecceDepartment of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, LecceDepartment of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, LecceIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna Italy; Department of Medical and Surgical Sciences (DIMEC) University of Bologna, BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna Italy; Department of Medical and Surgical Sciences (DIMEC) University of Bologna, BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaDepartment of Medical and Surgical Sciences (DIMEC) University of Bologna, BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna Italy; Department of Medical and Surgical Sciences (DIMEC) University of Bologna, BolognaIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna Italy; Department of Medical and Surgical Sciences (DIMEC) University of Bologna, BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna Italy; Department of Medical and Surgical Sciences (DIMEC) University of Bologna, BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaIRCCS Azienda Ospedaliero-Universitaria di BolognaDepartment of Medical and Surgical Sciences (DIMEC) University of Bologna, BolognaIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna Italy; Department of Medical and Surgical Sciences (DIMEC) University of Bologna, BolognaIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna Italy; Department of Medical and Surgical Sciences (DIMEC) University of Bologna, BolognaIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna Italy; Department of Medical and Surgical Sciences (DIMEC) University of Bologna, BolognaDepartment of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, LecceIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna Italy; Department of Medical and Surgical Sciences (DIMEC) University of Bologna, BolognaIRCCS Azienda Ospedaliero-Universitaria di Bologna Plasma metabolomics analysis was performed on 44 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r/B-NHL) infused with approved CD19.CAR-T cell products at the time of pre-lymphodepletion (PLD) and at day +1, +7, and +30 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 day+1, 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 day+30, discriminant analysis found two clusters in a subgroup of patients, one with CR lasting one year after therapy, and another who relapsed within one 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. https://haematologica.org/article/view/11875 |
| spellingShingle | Serena De Matteis Laura Del Coco Federica De Castro Anna Maria Giudetti Beatrice Casadei Francesco 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 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 Haematologica |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://haematologica.org/article/view/11875 |
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