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

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 associated with poor response to treatment. We tested whether an MYC-driven polyamine...

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Main Authors: Fahrmann, Johannes (Author) , Saini, Neeraj Y. (Author) , Chia-Chi, Chang (Author) , Irajizad, Ehsan (Author) , Strati, Paolo (Author) , Nair, Ranjit (Author) , Fayad, Luis E. (Author) , Ahmed, Sairah (Author) , Lee, Hun Ju (Author) , Iyer, Swaminathan (Author) , Steiner, Raphael (Author) , Vykoukal, Jody (Author) , Wu, Ranran (Author) , Dennison, Jennifer B. (Author) , Nastoupil, Loretta (Author) , Jain, Preetesh (Author) , Wang, Michael (Author) , Green, Michael (Author) , Westin, Jason (Author) , Blumenberg, Viktoria (Author) , Davila, Marco (Author) , Champlin, Richard (Author) , Shpall, Elizabeth J. (Author) , Kebriaei, Partow (Author) , Flowers, Christopher R. (Author) , Jain, Michael (Author) , Jenq, Robert (Author) , Stein-Thöringer, Christoph (Author) , Subklewe, Marion (Author) , Neelapu, Sattva S. (Author) , Hanash, Sam (Author)
Format: Article (Journal)
Language:English
Published: 15 November 2022
In: Cell reports. Medicine
Year: 2022, Volume: 3, Issue: 11, Pages: 1-14
ISSN:2666-3791
DOI:10.1016/j.xcrm.2022.100720
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.xcrm.2022.100720
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2666379122002634
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Author Notes:Johannes F. Fahrmann, Neeraj Y. Saini, Chang Chia-Chi, Ehsan Irajizad, Paolo Strati, Ranjit Nair, Luis E. Fayad, Sairah Ahmed, Hun Ju Lee, Swaminathan Iyer, Raphael Steiner, Jody Vykoukal, Ranran Wu, Jennifer B. Dennison, Loretta Nastoupil, Preetesh Jain, Michael Wang, Michael Green, Jason Westin, Viktoria Blumenberg, Marco Davila, Richard Champlin, Elizabeth J. Shpall, Partow Kebriaei, Christopher R. Flowers, Michael Jain, Robert Jenq, Christoph K. Stein-Thoeringer, Marion Subklewe, Sattva S. Neelapu, and Sam Hanash
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Summary: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 associated 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 acetylated polyamines were associated with non-durable response. Concordantly, increased expression of spermidine 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 independent 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.
Item Description:Gesehen am 09.11.2023
Physical Description:Online Resource
ISSN:2666-3791
DOI:10.1016/j.xcrm.2022.100720

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