PMID- 36508286
OWN - NLM
STAT- MEDLINE
DCOM- 20230824
LR  - 20240227
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 7
IP  - 17
DP  - 2023 Sep 12
TI  - Chimeric antigen receptor T-cell therapy yields similar outcomes in patients with 
      and without cytokine release syndrome.
PG  - 4765-4772
LID - 10.1182/bloodadvances.2022008937 [doi]
AB  - Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment 
      of many patients with aggressive relapsed or refractory large B-cell lymphoma 
      (LBCL). Treatment can be complicated by clinically evident cytokine release 
      syndrome (CRS), which is characterized by the development of fever, hypoxia, and 
      hypotension, and can be life-threatening. Most patients treated with CAR-T cells 
      develop CRS, which is thought to represent an immune phenomenon. It was 
      previously unknown whether patients who did not develop CRS had reduced CAR-T 
      cell activity and were therefore likely to have worse outcomes. We conducted a 
      multicenter retrospective analysis of 352 adult patients treated at 8 academic 
      medical centers in the United States who received axicabtagene ciloleucel or 
      tisagenlecleucel for the treatment of LBCL. The outcomes of interest included 
      progression-free survival, overall survival, complete response rate, and overall 
      response rate. Of the included patients, 262 (74.4%) developed CRS. There was no 
      significant difference in progression-free survival (P = .99) or overall survival 
      (P = .16) between patients who developed CRS and those who did not develop CRS. 
      Peak ferritin levels >5000 ng/mL during treatment and lactate dehydrogenase 
      levels greater than the institutional upper limit of normal before 
      lymphodepleting chemotherapy were associated with significantly worse 
      progression-free and overall survival in the multivariate analysis. There was no 
      significant difference in the complete response or overall response rates between 
      patients who did and did not develop CRS. In this retrospective analysis, we 
      report that patients who develop CRS have clinical outcomes similar to those of 
      patients without CRS treated with commercial anti-CD19 CAR-T cells.
CI  - (c) 2023 by The American Society of Hematology. Licensed under Creative Commons 
      Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), 
      permitting only noncommercial, nonderivative use with attribution. All other 
      rights reserved.
FAU - Bhaskar, Shakthi T
AU  - Bhaskar ST
AUID- ORCID: 0000-0003-4528-6367
AD  - Vanderbilt-Ingram Cancer Center, Nashville, TN.
FAU - Patel, Vivek G
AU  - Patel VG
AD  - Vanderbilt-Ingram Cancer Center, Nashville, TN.
FAU - Porter, David L
AU  - Porter DL
AD  - Blood and Marrow Transplant and Cellular Therapy Program, Abramson Cancer Center, 
      The University of Pennsylvania, Philadelphia, PA.
FAU - Schuster, Stephen J
AU  - Schuster SJ
AD  - Blood and Marrow Transplant and Cellular Therapy Program, Abramson Cancer Center, 
      The University of Pennsylvania, Philadelphia, PA.
FAU - Nastoupil, Loretta J
AU  - Nastoupil LJ
AUID- ORCID: 0000-0001-6071-8610
AD  - Division of Cancer Medicine, Department of Lymphoma/Myeloma, The University of 
      Texas MD Anderson Cancer Center, Houston, TX.
FAU - Perales, Miguel-Angel
AU  - Perales MA
AUID- ORCID: 0000-0002-5910-4571
AD  - Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY.
FAU - Tomas, Ana Alarcon
AU  - Tomas AA
AUID- ORCID: 0000-0002-6290-1061
AD  - Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY.
AD  - Ph.D Program in Signals Integration and Modulation in Biomedicine, Cell Therapy, 
      and Translational Medicine, University of Murcia, Murcia, Spain.
FAU - Bishop, Michael R
AU  - Bishop MR
AD  - The David and Etta Jonas Center for Cellular Therapy, University of Chicago, 
      Chicago, IL.
FAU - McGuirk, Joseph P
AU  - McGuirk JP
AUID- ORCID: 0000-0002-0539-4796
AD  - Division of Hematologic Malignancies and Cellular Therapeutics, Department of 
      Medicine, The University of Kansas, Kansas City, KS.
FAU - Maziarz, Richard T
AU  - Maziarz RT
AD  - Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & 
      Science University, Portland, OR.
FAU - Chen, Andy I
AU  - Chen AI
AD  - Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & 
      Science University, Portland, OR.
FAU - Bachanova, Veronika
AU  - Bachanova V
AD  - Division of Hematology, Oncology, Transplantation, Department of Medicine, 
      University of Minnesota, Minneapolis, MN.
FAU - Maakaron, Joseph E
AU  - Maakaron JE
AD  - Division of Hematology, Oncology, Transplantation, Department of Medicine, 
      University of Minnesota, Minneapolis, MN.
FAU - Riedell, Peter A
AU  - Riedell PA
AUID- ORCID: 0000-0003-2719-0580
AD  - The David and Etta Jonas Center for Cellular Therapy, University of Chicago, 
      Chicago, IL.
FAU - Oluwole, Olalekan O
AU  - Oluwole OO
AUID- ORCID: 0000-0001-8525-9641
AD  - Vanderbilt-Ingram Cancer Center, Nashville, TN.
LA  - eng
GR  - P01 CA065493/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - UL1 TR002494/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Receptors, Chimeric Antigen)
RN  - 0 (Antigens, CD19)
SB  - IM
MH  - Adult
MH  - Humans
MH  - United States
MH  - *Receptors, Chimeric Antigen/therapeutic use
MH  - Cytokine Release Syndrome/etiology/therapy
MH  - Retrospective Studies
MH  - *Lymphoma, Large B-Cell, Diffuse/drug therapy
MH  - Antigens, CD19
MH  - Cell- and Tissue-Based Therapy
PMC - PMC10468356
COIS- Conflict-of-interest disclosure: D.L.P. reports honorarium for consulting or 
      advisory board participation from Novartis, Kite/Gilead, Incyte, Gerson Lehrman 
      Group, Janssen (Johnson & Johnson), Jazz, Adepcet Bio, DeCART, Bristol Myers 
      Squibb (BMS), bluebird bio, Kadmon, Angiocrine, and Mirror Biologics; research 
      support from Novartis; patents and royalties related to CAR T-cell therapy for 
      malignancies licensed to Novartis and Tmunity; and stock/equity in 
      Genentech/Roche (spouse former employment). S.J.S. reports membership on the 
      advisory board for BeiGene, Celgene/BMS/Juno, Genentech, Roche, Genmab, Incyte, 
      Janssen, MorphoSys, Mustang Biotech, and Novartis; research grants from 
      Genentech/Roche, Merck, and Novartis; is a member on the steering committee for 
      Fate Therapeutics, Legend Biotech, and Nordic Nanovector; received honoraria from 
      Incyte and Novartis; consults for Novartis; and reports a patent on "combination 
      therapies of CAR and PD-1 inhibitors" with royalties paid to Novartis. L.J.N. 
      reports honoraria from ADC Therapeutics, BMS, Caribou Biosciences, Epizyme, 
      Genentech, Gilead/Kite, Janssen, MorphoSys, Novartis, and Takeda, and research 
      support from BMS, Caribou Biosciences, Epizyme, Genentech, Genmab, Gilead/Kite, 
      Janssen, IGM Biosciences, Novartis, and Takeda. M.-A.P. reports honoraria from 
      AbbVie, AlloVir, Astellas, BMS, Celgene, Equilium, Exevir, Incyte, Karyopharm, 
      Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Novartis, Nektar Therapeutics, 
      Omeros, OrcaBio, Takeda, VectivBio AG, and Vor Biopharma; serves on data and 
      safety monitoring boards (DSMBs) for Cidara Therapeutics, Medigene, Sellas Life 
      Sciences, and Servier, serves on the scientific advisory board of NexImmune; has 
      ownership interests in NexImmune and Omeros; and received institutional research 
      support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar 
      Therapeutics, and Novartis. M.R.B. reports membership on an advisory board or 
      consultancy for Kite/Gilead, Novartis, CRISPR Therapeutics, Autolus Therapeutics, 
      BMS, Incyte, Sana Biotechnology, Iovance Biotherapeutics, and served on a 
      speakers bureau for BMS, Sanofi, Agios, and Incyte. J.P.M. reports honoraria for 
      consulting or advisory board participation for Kite, BMS, Novartis, Caribou, 
      AlloVir, NEKTAR, Janssen. R.T.M. is an advisor or consultant for AlloVir, CRISPR 
      Therapeutics, Incyte, and Novartis; reports honoraria from Incyte; research 
      support from AlloVir, and Novartis; participation in a data and safety monitoring 
      board for Athersys, Vor Pharma, and Novartis; a patent with Athersys, Inc; 
      and serves on the scientific advisory board of Artiva and Lyrik Therapeutics. 
      A.I.C. reports institutional research funding from Novartis and Fate Therapeutics 
      and is an advisor for Kite. V.B. reports research funding from Incyte, BMS, 
      Gamide Cell, Incyte, Citius Pharmaceuticals, Fate Therapeutics; consultancy with 
      Incyte, Karyopharma, ADC, BMS, Gamida Cell, Fate Therapeutics and DSMB; and 
      membership at Miltenyi Biotec. J.E.M. receives institutional research funding 
      from Gilead, CRISPR, Precision BioSciences, Scripps, Fate Therapeutics, ADC. 
      P.A.R. reports research support/funding from BMS, Kite Pharma, Inc/Gilead, 
      MorphoSys, Calibr, Tessa Therapeutics, Fate Therapeutics, Xencor, and Novartis 
      Pharmaceuticals Corporation; speaker's bureau from Kite Pharma, Inc/Gilead; 
      consultancy on advisory boards of AbbVie, Novartis Pharmaceuticals Corporation, 
      BMS, Janssen, BeiGene, Karyopharm Therapeutics Inc, Takeda Pharmaceutical 
      Company, Kite Pharma, Inc/Gilead, Sana Biotechnology, Nektar Therapeutics, 
      Intellia Therapeutics, and Bayer; and received honoraria from Novartis 
      Pharmaceuticals Corporation. O.O.O. reports consultancy with and serves on the 
      advisory boards for Pfizer, Kite, Gilead, AbbVie, Janssen, TGR Therapeutics, ADC, 
      Novartis, Curio Science, Nektar; receives institution funding from Kite, Pfizer, 
      Daichi Sankyo, Allogene; and receives honoraria from Pfizer and Gilead. The 
      remaining authors declare no competing financial interests.
EDAT- 2022/12/13 06:00
MHDA- 2023/08/24 06:42
PMCR- 2022/12/13
CRDT- 2022/12/12 12:23
PHST- 2022/11/17 00:00 [accepted]
PHST- 2022/09/12 00:00 [received]
PHST- 2023/08/24 06:42 [medline]
PHST- 2022/12/13 06:00 [pubmed]
PHST- 2022/12/12 12:23 [entrez]
PHST- 2022/12/13 00:00 [pmc-release]
AID - 493710 [pii]
AID - 10.1182/bloodadvances.2022008937 [doi]
PST - ppublish
SO  - Blood Adv. 2023 Sep 12;7(17):4765-4772. doi: 10.1182/bloodadvances.2022008937.