TY - JOUR
T1 - A polyamine-centric, blood-based metabolite panel predictive of poor response to CAR-T cell therapy in large B cell lymphoma
AU - Fahrmann, Johannes F.
AU - Saini, Neeraj Y.
AU - Chia-Chi, Chang
AU - Irajizad, Ehsan
AU - Strati, Paolo
AU - Nair, Ranjit
AU - Fayad, Luis E.
AU - Ahmed, Sairah
AU - Lee, Hun Ju
AU - Iyer, Swaminathan
AU - Steiner, Raphael
AU - Vykoukal, Jody
AU - Wu, Ranran
AU - Dennison, Jennifer B.
AU - Nastoupil, Loretta
AU - Jain, Preetesh
AU - Wang, Michael
AU - Green, Michael
AU - Westin, Jason
AU - Blumenberg, Viktoria
AU - Davila, Marco
AU - Champlin, Richard
AU - Shpall, Elizabeth J.
AU - Kebriaei, Partow
AU - Flowers, Christopher R.
AU - Jain, Michael
AU - Jenq, Robert
AU - Stein-Thoeringer, Christoph K.
AU - Subklewe, Marion
AU - Neelapu, Sattva S.
AU - Hanash, Sam
N1 - Funding Information:
This work was supported by the generous philanthropic contributions to the University of Texas MD Anderson Cancer Center Moon Shots Program and an NCI Cancer Center Support Grant to the University of Texas MD Anderson Cancer Center ( P30 CA016672 ).
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/11/15
Y1 - 2022/11/15
N2 - 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.
AB - 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.
KW - CAR-T cell therapy
KW - biomarker
KW - large B cell lymphoma
KW - liquid biopsy
KW - metabolites
KW - prognostic
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U2 - 10.1016/j.xcrm.2022.100720
DO - 10.1016/j.xcrm.2022.100720
M3 - Article
C2 - 36384092
AN - SCOPUS:85142200235
SN - 2666-3791
VL - 3
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 11
M1 - 100720
ER -