Faculty, Staff and Student Publications
Publication Date
11-15-2022
Journal
Cell Reports Medicine
DOI
10.1016/j.xcrm.2022.100720
PMID
36384092
PMCID
PMC9729795
PubMedCentral® Posted Date
November 2022
PubMedCentral® Full Text Version
Post-print
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 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.
Keywords
Humans, Receptors, Chimeric Antigen, Polyamines, Antigens, CD19, Lymphoma, Large B-Cell, Diffuse, Cell- and Tissue-Based Therapy
Published Open-Access
yes
Recommended Citation
Fahrmann, Johannes F; Saini, Neeraj Y; Chia-Chi, Chang; et al., "A Polyamine-Centric, Blood-Based Metabolite Panel Predictive of Poor Response to CAR-T Cell Therapy in Large B Cell Lymphoma" (2022). Faculty, Staff and Student Publications. 956.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/956
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