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 - 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
UR - http://www.scopus.com/inward/record.url?scp=85142200235&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85142200235&partnerID=8YFLogxK
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 -