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

Fahrmann, Johannes F.; Saini, Neeraj Y.; Chia-Chi, Chang; Irajizad, Ehsan; Strati, Paolo; Nair, Ranjit; Fayad, Luis E.; Ahmed, Sairah; Lee, Hun Ju; Iyer, Swaminathan; Steiner, Raphael; Vykoukal, Jody; Wu, Ranran; Dennison, Jennifer B.; Nastoupil, Loretta; Jain, Preetesh; Wang, Michael; Green, Michael; Westin, Jason; Blumenberg, Viktoria; Davila, Marco; Champlin, Richard; Shpall, Elizabeth J.; Kebriaei, Partow; Flowers, Christopher R.; Jain, Michael; Jenq, Robert; Stein-Thoeringer, Christoph K.; Subklewe, Marion; Neelapu, Sattva S. und Hanash, Sam (2022): A polyamine-centric, blood-based metabolite panel predictive of poor response to CAR-T cell therapy in B cell lymphoma. In: Cell Reports Medicine, Bd. 3, Nr. 11, 100720

Abstract

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed or refractory (r/r) large B cell lymphoma (LBCL) results in durable response in only a subset of patients. MYC overexpression in LBCL tumors is asso-ciated with poor response to treatment. We tested whether an MYC-driven polyamine signature, as a liquid biopsy, is predictive of response to anti-CD19 CAR-T therapy in patients with r/r LBCL. Elevated plasma acet-ylated polyamines were associated with non-durable response. Concordantly, increased expression of sper-midine synthase, a key enzyme that regulates levels of acetylated spermidine, was prognostic for survival in r/r LBCL. A broad metabolite screen identified additional markers that resulted in a 6-marker panel (6MetP) consisting of acetylspermidine, diacetylspermidine, and lysophospholipids, which was validated in an inde-pendent set from another institution as predictive of non-durable response to CAR-T therapy. A polyamine centric metabolomics liquid biopsy panel has predictive value for response to CAR-T therapy in r/r LBCL.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Chemie und Pharmazie > Department Biochemie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit ; 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 2666-3791
• Sprache: Englisch