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/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.
Authors
- Noemi Laprovitera (ORCID: https://orcid.org/0000-0002-2737-4665)
- Federica De Castro (ORCID: https://orcid.org/0000-0001-5060-293X)
- Barbara Sinigaglia (ORCID: https://orcid.org/0000-0003-1109-4244)
- Paolo Garagnani (ORCID: https://orcid.org/0000-0002-4161-3626)
- Chiara Pirazzini (ORCID: https://orcid.org/0000-0001-8248-0295)
- Anna Maria Giudetti (ORCID: https://orcid.org/0000-0002-9204-040X)
- Manuela Ferracin (ORCID: https://orcid.org/0000-0002-1595-6887)
- Francesco Paolo Fanizzi (ORCID: https://orcid.org/0000-0003-3073-5772)
- Laura Del Coco (ORCID: https://orcid.org/0000-0002-4805-7538)
- Irene Salamon (ORCID: https://orcid.org/0000-0003-2689-4340)
- Massimiliano Bonafè (ORCID: https://orcid.org/0000-0002-5218-6551)
- Elisa Dan (ORCID: https://orcid.org/0000-0002-3071-363X)
- Salvatore Nicola Bertuccio (ORCID: https://orcid.org/0000-0002-5428-6716)
- Cinzia Pellegrini (ORCID: https://orcid.org/0000-0002-5223-4429)
- Gianluca Storci (ORCID: https://orcid.org/0000-0001-5145-3091)
- Enrica Tomassini (ORCID: https://orcid.org/0000-0003-1931-2197)
- Margherita Ursi (ORCID: https://orcid.org/0000-0001-8821-9397)
- F Iannotta
- Marcello Roberto
- Francesco De Felice (ORCID: https://orcid.org/0000-0002-6369-3006)
- Enrico Maffini (ORCID: https://orcid.org/0000-0001-7356-2328)
- Beatrice Casadei (ORCID: https://orcid.org/0000-0002-4453-6064)
- Francesca Vaglio
- Serena De Matteis (ORCID: https://orcid.org/0000-0001-9219-4081)
- Francesca Bonifazi (ORCID: https://orcid.org/0000-0003-1544-9911)
- Daria Messelodi
- Maria Naddeo (ORCID: https://orcid.org/0000-0001-6376-7450)
- Pier Luigi Zinzani (ORCID: https://orcid.org/0000-0002-2112-2651)
- Francesco Barbato (ORCID: https://orcid.org/0000-0001-6364-3589)
- Elena Campanini
- Marta Tassoni
Institutions
- University of Salento (IT)
- Azienda USL di Bologna (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- University of Bologna (IT)
Publication Details
- Journal
- Haematologica
- Published
- 2024-12-19
- DOI
- https://doi.org/10.3324/haematol.2024.285154
- Citations
- 3
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.85
Funders
- Ministero della Salute
- National Institutes of Health
- Common Fund