PMID- 36384092
OWN - NLM
STAT- MEDLINE
DCOM- 20221121
LR  - 20230421
IS  - 2666-3791 (Electronic)
IS  - 2666-3791 (Linking)
VI  - 3
IP  - 11
DP  - 2022 Nov 15
TI  - A polyamine-centric, blood-based metabolite panel predictive of poor response to 
      CAR-T cell therapy in large B cell lymphoma.
PG  - 100720
LID - S2666-3791(22)00263-4 [pii]
LID - 10.1016/j.xcrm.2022.100720 [doi]
LID - 100720
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.
CI  - Copyright (c) 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Fahrmann, Johannes F
AU  - Fahrmann JF
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, 6767 Bertner Avenue, Houston, TX 77030, USA.
FAU - Saini, Neeraj Y
AU  - Saini NY
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; 
      Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Chia-Chi, Chang
AU  - Chia-Chi C
AD  - Department of Genomic Medicine, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Irajizad, Ehsan
AU  - Irajizad E
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, 6767 Bertner Avenue, Houston, TX 77030, USA; Department of 
      Biostatistics, The University of Texas MD Anderson Cancer Center, 6767 Bertner 
      Avenue, Houston, TX 77030, USA.
FAU - Strati, Paolo
AU  - Strati P
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Nair, Ranjit
AU  - Nair R
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Fayad, Luis E
AU  - Fayad LE
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Ahmed, Sairah
AU  - Ahmed S
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Lee, Hun Ju
AU  - Lee HJ
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Iyer, Swaminathan
AU  - Iyer S
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Steiner, Raphael
AU  - Steiner R
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Vykoukal, Jody
AU  - Vykoukal J
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, 6767 Bertner Avenue, Houston, TX 77030, USA.
FAU - Wu, Ranran
AU  - Wu R
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, 6767 Bertner Avenue, Houston, TX 77030, USA.
FAU - Dennison, Jennifer B
AU  - Dennison JB
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, 6767 Bertner Avenue, Houston, TX 77030, USA.
FAU - Nastoupil, Loretta
AU  - Nastoupil L
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Jain, Preetesh
AU  - Jain P
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Wang, Michael
AU  - Wang M
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Green, Michael
AU  - Green M
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Westin, Jason
AU  - Westin J
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Blumenberg, Viktoria
AU  - Blumenberg V
AD  - Department of Medicine III, University Hospital, LMU Munich, 81377 Munich, 
      Germany; National Center for Tumor Diseases (NCT), Neuenheimer Feld 460, 69120 
      Heidelberg, Germany.
FAU - Davila, Marco
AU  - Davila M
AD  - Department of Blood and Marrow Transplant and Cellular Therapy, Moffitt Cancer 
      Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA.
FAU - Champlin, Richard
AU  - Champlin R
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Shpall, Elizabeth J
AU  - Shpall EJ
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Kebriaei, Partow
AU  - Kebriaei P
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Flowers, Christopher R
AU  - Flowers CR
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Jain, Michael
AU  - Jain M
AD  - Department of Blood and Marrow Transplant and Cellular Therapy, Moffitt Cancer 
      Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA.
FAU - Jenq, Robert
AU  - Jenq R
AD  - Department of Genomic Medicine, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
FAU - Stein-Thoeringer, Christoph K
AU  - Stein-Thoeringer CK
AD  - National Center for Tumor Diseases (NCT), Neuenheimer Feld 460, 69120 Heidelberg, 
      Germany; German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 
      Heidelberg, Germany.
FAU - Subklewe, Marion
AU  - Subklewe M
AD  - Department of Medicine III, University Hospital, LMU Munich, 81377 Munich, 
      Germany; German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 
      Heidelberg, Germany; Laboratory for Translational Cancer Immunology, Gene Center 
      of the LMU Munich, Munich, Germany. Electronic address: 
      marion.subklewe@med.uni-muenchen.de.
FAU - Neelapu, Sattva S
AU  - Neelapu SS
AD  - Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Electronic address: 
      sneelapu@mdanderson.org.
FAU - Hanash, Sam
AU  - Hanash S
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, 6767 Bertner Avenue, Houston, TX 77030, USA. Electronic address: 
      shanash@mdanderson.org.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cell Rep Med
JT  - Cell reports. Medicine
JID - 101766894
RN  - 0 (Receptors, Chimeric Antigen)
RN  - 0 (Polyamines)
RN  - 0 (Antigens, CD19)
SB  - IM
MH  - Humans
MH  - *Receptors, Chimeric Antigen
MH  - Polyamines
MH  - Antigens, CD19
MH  - *Lymphoma, Large B-Cell, Diffuse/genetics
MH  - Cell- and Tissue-Based Therapy
PMC - PMC9729795
OTO - NOTNLM
OT  - CAR-T cell therapy
OT  - biomarker
OT  - large B cell lymphoma
OT  - liquid biopsy
OT  - metabolites
OT  - prognostic
COIS- Declaration of interests An Invention Disclosure Report related to findings 
      reported herein has been submitted to the University of Texas. M.S. has received 
      industry research support from Amgen, Gilead, Miltenyi Biotec, Morphosys, Roche, 
      and Seattle Genetics and has served as a consultant/advisor to Amgen, BMS, 
      Celgene, Gilead, Pfizer, Novartis, and Roche. She sits on the advisory boards of 
      Amgen, Celgene, Gilead, Janssen, Novartis, Pfizer, and Seattle Genetics and 
      serves on the speakers' bureau at Amgen, Celgene, Gilead, Janssen, and Pfizer. 
      N.Y.S. has intellectual property rights in the field of cellular immunotherapy 
      and microbiome. S.S.N. received personal fees from Kite, a Gilead Company, Merck, 
      Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell 
      Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, 
      Bluebird Bio, and Unum Therapeutics; research support from Kite, a Gilead 
      Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus 
      Therapeutics, Unum Therapeutics, Allogene Therapeutics, Precision Biosciences, 
      and Acerta; royalties from Takeda Pharmaceuticals; and has intellectual property 
      rights related to cell therapy. M.G. reports research funding from Sanofi, 
      Kite/Gilead, Abbvie, and Allogene, honoraria from Tessa Therapeutics and Daiichi 
      Sankyo, and stock ownership of KDAc Therapeutics. P.S. received research support 
      from Astrazeneca-Acerta and from ALX Oncology and is a consultant for 
      Roche-Genentech and Hutchinson MediPharma. S.S.N. has received personal fees from 
      Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, 
      Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend 
      Biotech, Adicet Bio, Calibr, Unum Therapeutics, and Bluebird Bio; research 
      support from Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, 
      Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics, Allogene Therapeutics, 
      Precision Biosciences, and Acerta; and patents, royalties, or other intellectual 
      property from Takeda Pharmaceuticals.
EDAT- 2022/11/18 06:00
MHDA- 2022/11/22 06:00
PMCR- 2022/11/15
CRDT- 2022/11/17 09:27
PHST- 2021/11/23 00:00 [received]
PHST- 2022/06/06 00:00 [revised]
PHST- 2022/07/20 00:00 [accepted]
PHST- 2022/11/17 09:27 [entrez]
PHST- 2022/11/18 06:00 [pubmed]
PHST- 2022/11/22 06:00 [medline]
PHST- 2022/11/15 00:00 [pmc-release]
AID - S2666-3791(22)00263-4 [pii]
AID - 100720 [pii]
AID - 10.1016/j.xcrm.2022.100720 [doi]
PST - ppublish
SO  - Cell Rep Med. 2022 Nov 15;3(11):100720. doi: 10.1016/j.xcrm.2022.100720.