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Cytokine release syndrome

MedGen UID:
215297
•Concept ID:
C0948245
•
Disease or Syndrome
Synonyms: Cytokine Release Syndrome; Cytokine Release Syndromes; Cytokine Storm Syndrome; Hypercytokinemia; Hypercytokinemias
SNOMED CT: CRS - cytokine release syndrome (710027002); Cytokine release syndrome (710027002); Cytokine-associated toxicity (710027002)
 
Monarch Initiative: MONDO:0600008

Definition

A syndrome that occurs after therapeutic infusion of antibodies into the blood and is characterized by nausea, headache, tachycardia, hypotension, rash, and shortness of breath. It is caused by the release of cytokines from the cells that are targeted by the antibodies. Most patients experience a mild to moderate reaction; however, the reaction may be severe and life-threatening. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCytokine release syndrome

Professional guidelines

PubMed

Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA).
Hayden PJ, Roddie C, Bader P, Basak GW, Bonig H, Bonini C, Chabannon C, Ciceri F, Corbacioglu S, Ellard R, Sanchez-Guijo F, Jäger U, Hildebrandt M, Hudecek M, Kersten MJ, Köhl U, Kuball J, Mielke S, Mohty M, Murray J, Nagler A, Rees J, Rioufol C, Saccardi R, Snowden JA, Styczynski J, Subklewe M, Thieblemont C, Topp M, Ispizua ÁU, Chen D, Vrhovac R, Gribben JG, Kröger N, Einsele H, Yakoub-Agha I
Ann Oncol 2022 Mar;33(3):259-275. Epub 2021 Dec 16 doi: 10.1016/j.annonc.2021.12.003. PMID: 34923107
Side-effect management of chimeric antigen receptor (CAR) T-cell therapy.
Schubert ML, Schmitt M, Wang L, Ramos CA, Jordan K, Müller-Tidow C, Dreger P
Ann Oncol 2021 Jan;32(1):34-48. Epub 2020 Oct 21 doi: 10.1016/j.annonc.2020.10.478. PMID: 33098993
Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management.
Brudno JN, Kochenderfer JN
Blood Rev 2019 Mar;34:45-55. Epub 2018 Nov 14 doi: 10.1016/j.blre.2018.11.002. PMID: 30528964Free PMC Article

Recent clinical studies

Etiology

Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma.
Chari A, Minnema MC, Berdeja JG, Oriol A, van de Donk NWCJ, Rodríguez-Otero P, Askari E, Mateos MV, Costa LJ, Caers J, Verona R, Girgis S, Yang S, Goldsmith RB, Yao X, Pillarisetti K, Hilder BW, Russell J, Goldberg JD, Krishnan A
N Engl J Med 2022 Dec 15;387(24):2232-2244. Epub 2022 Dec 10 doi: 10.1056/NEJMoa2204591. PMID: 36507686
GPRC5D-Targeted CAR T Cells for Myeloma.
Mailankody S, Devlin SM, Landa J, Nath K, Diamonte C, Carstens EJ, Russo D, Auclair R, Fitzgerald L, Cadzin B, Wang X, Sikder D, Senechal B, Bermudez VP, Purdon TJ, Hosszu K, McAvoy DP, Farzana T, Mead E, Wilcox JA, Santomasso BD, Shah GL, Shah UA, Korde N, Lesokhin A, Tan CR, Hultcrantz M, Hassoun H, Roshal M, Sen F, Dogan A, Landgren O, Giralt SA, Park JH, Usmani SZ, Rivière I, Brentjens RJ, Smith EL
N Engl J Med 2022 Sep 29;387(13):1196-1206. doi: 10.1056/NEJMoa2209900. PMID: 36170501Free PMC Article
Malignancy-associated haemophagocytic lymphohistiocytosis.
Setiadi A, Zoref-Lorenz A, Lee CY, Jordan MB, Chen LYC
Lancet Haematol 2022 Mar;9(3):e217-e227. Epub 2022 Jan 31 doi: 10.1016/S2352-3026(21)00366-5. PMID: 35101205
ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells.
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS
Biol Blood Marrow Transplant 2019 Apr;25(4):625-638. Epub 2018 Dec 25 doi: 10.1016/j.bbmt.2018.12.758. PMID: 30592986
Cytokine release syndrome.
Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M, Kochanek M, Böll B, von Bergwelt-Baildon MS
J Immunother Cancer 2018 Jun 15;6(1):56. doi: 10.1186/s40425-018-0343-9. PMID: 29907163Free PMC Article

Diagnosis

Cytokine Storm Syndrome.
Cron RQ, Goyal G, Chatham WW
Annu Rev Med 2023 Jan 27;74:321-337. Epub 2022 Oct 13 doi: 10.1146/annurev-med-042921-112837. PMID: 36228171
Castleman disease and TAFRO syndrome.
Masaki Y, Arita K, Sakai T, Takai K, Aoki S, Kawabata H
Ann Hematol 2022 Mar;101(3):485-490. Epub 2022 Jan 19 doi: 10.1007/s00277-022-04762-6. PMID: 35044513Free PMC Article
Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.
Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, Stewart AK, Hari P, Htut M, Lesokhin A, Deol A, Munshi NC, O'Donnell E, Avigan D, Singh I, Zudaire E, Yeh TM, Allred AJ, Olyslager Y, Banerjee A, Jackson CC, Goldberg JD, Schecter JM, Deraedt W, Zhuang SH, Infante J, Geng D, Wu X, Carrasco-Alfonso MJ, Akram M, Hossain F, Rizvi S, Fan F, Lin Y, Martin T, Jagannath S
Lancet 2021 Jul 24;398(10297):314-324. Epub 2021 Jun 24 doi: 10.1016/S0140-6736(21)00933-8. PMID: 34175021
A review of cancer immunotherapy toxicity.
Kennedy LB, Salama AKS
CA Cancer J Clin 2020 Mar;70(2):86-104. Epub 2020 Jan 16 doi: 10.3322/caac.21596. PMID: 31944278
Cytokine release syndrome.
Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M, Kochanek M, Böll B, von Bergwelt-Baildon MS
J Immunother Cancer 2018 Jun 15;6(1):56. doi: 10.1186/s40425-018-0343-9. PMID: 29907163Free PMC Article

Therapy

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma.
Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, Khan C, Wróbel T, Offner F, Trněný M, Wu SJ, Cartron G, Hertzberg M, Sureda A, Perez-Callejo D, Lundberg L, Relf J, Dixon M, Clark E, Humphrey K, Hutchings M
N Engl J Med 2022 Dec 15;387(24):2220-2231. Epub 2022 Dec 11 doi: 10.1056/NEJMoa2206913. PMID: 36507690
GPRC5D-Targeted CAR T Cells for Myeloma.
Mailankody S, Devlin SM, Landa J, Nath K, Diamonte C, Carstens EJ, Russo D, Auclair R, Fitzgerald L, Cadzin B, Wang X, Sikder D, Senechal B, Bermudez VP, Purdon TJ, Hosszu K, McAvoy DP, Farzana T, Mead E, Wilcox JA, Santomasso BD, Shah GL, Shah UA, Korde N, Lesokhin A, Tan CR, Hultcrantz M, Hassoun H, Roshal M, Sen F, Dogan A, Landgren O, Giralt SA, Park JH, Usmani SZ, Rivière I, Brentjens RJ, Smith EL
N Engl J Med 2022 Sep 29;387(13):1196-1206. doi: 10.1056/NEJMoa2209900. PMID: 36170501Free PMC Article
CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy.
Pan K, Farrukh H, Chittepu VCSR, Xu H, Pan CX, Zhu Z
J Exp Clin Cancer Res 2022 Mar 31;41(1):119. doi: 10.1186/s13046-022-02327-z. PMID: 35361234Free PMC Article
The cytokine storm and COVID-19.
Hu B, Huang S, Yin L
J Med Virol 2021 Jan;93(1):250-256. Epub 2020 Sep 30 doi: 10.1002/jmv.26232. PMID: 32592501Free PMC Article
ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells.
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS
Biol Blood Marrow Transplant 2019 Apr;25(4):625-638. Epub 2018 Dec 25 doi: 10.1016/j.bbmt.2018.12.758. PMID: 30592986

Prognosis

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma.
Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, Khan C, Wróbel T, Offner F, Trněný M, Wu SJ, Cartron G, Hertzberg M, Sureda A, Perez-Callejo D, Lundberg L, Relf J, Dixon M, Clark E, Humphrey K, Hutchings M
N Engl J Med 2022 Dec 15;387(24):2220-2231. Epub 2022 Dec 11 doi: 10.1056/NEJMoa2206913. PMID: 36507690
COVID-19-associated coagulopathy and disseminated intravascular coagulation.
Asakura H, Ogawa H
Int J Hematol 2021 Jan;113(1):45-57. Epub 2020 Nov 7 doi: 10.1007/s12185-020-03029-y. PMID: 33161508Free PMC Article
CAR T-Cells.
Nair R, Westin J
Adv Exp Med Biol 2020;1244:215-233. doi: 10.1007/978-3-030-41008-7_10. PMID: 32301017
Cytokine release syndrome.
Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M, Kochanek M, Böll B, von Bergwelt-Baildon MS
J Immunother Cancer 2018 Jun 15;6(1):56. doi: 10.1186/s40425-018-0343-9. PMID: 29907163Free PMC Article
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY
N Engl J Med 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10 doi: 10.1056/NEJMoa1707447. PMID: 29226797Free PMC Article

Clinical prediction guides

Tumor inflammation-associated neurotoxicity.
Mahdi J, Dietrich J, Straathof K, Roddie C, Scott BJ, Davidson TB, Prolo LM, Batchelor TT, Campen CJ, Davis KL, Gust J, Lim M, Majzner RG, Park JR, Partap S, Ramakrishna S, Richards R, Schultz L, Vitanza NA, Wang LD, Mackall CL, Monje M
Nat Med 2023 Apr;29(4):803-810. Epub 2023 Apr 6 doi: 10.1038/s41591-023-02276-w. PMID: 37024595Free PMC Article
GPRC5D-Targeted CAR T Cells for Myeloma.
Mailankody S, Devlin SM, Landa J, Nath K, Diamonte C, Carstens EJ, Russo D, Auclair R, Fitzgerald L, Cadzin B, Wang X, Sikder D, Senechal B, Bermudez VP, Purdon TJ, Hosszu K, McAvoy DP, Farzana T, Mead E, Wilcox JA, Santomasso BD, Shah GL, Shah UA, Korde N, Lesokhin A, Tan CR, Hultcrantz M, Hassoun H, Roshal M, Sen F, Dogan A, Landgren O, Giralt SA, Park JH, Usmani SZ, Rivière I, Brentjens RJ, Smith EL
N Engl J Med 2022 Sep 29;387(13):1196-1206. doi: 10.1056/NEJMoa2209900. PMID: 36170501Free PMC Article
Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy.
Morris EC, Neelapu SS, Giavridis T, Sadelain M
Nat Rev Immunol 2022 Feb;22(2):85-96. Epub 2021 May 17 doi: 10.1038/s41577-021-00547-6. PMID: 34002066Free PMC Article
The 'cytokine storm': molecular mechanisms and therapeutic prospects.
Karki R, Kanneganti TD
Trends Immunol 2021 Aug;42(8):681-705. Epub 2021 Jul 1 doi: 10.1016/j.it.2021.06.001. PMID: 34217595Free PMC Article
Immunopathogenesis and treatment of cytokine storm in COVID-19.
Kim JS, Lee JY, Yang JW, Lee KH, Effenberger M, Szpirt W, Kronbichler A, Shin JI
Theranostics 2021;11(1):316-329. Epub 2021 Jan 1 doi: 10.7150/thno.49713. PMID: 33391477Free PMC Article

Recent systematic reviews

Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline.
Santomasso BD, Nastoupil LJ, Adkins S, Lacchetti C, Schneider BJ, Anadkat M, Atkins MB, Brassil KJ, Caterino JM, Chau I, Davies MJ, Ernstoff MS, Fecher L, Funchain P, Jaiyesimi I, Mammen JS, Naidoo J, Naing A, Phillips T, Porter LD, Reichner CA, Seigel C, Song JM, Spira A, Suarez-Almazor M, Swami U, Thompson JA, Vikas P, Wang Y, Weber JS, Bollin K, Ghosh M
J Clin Oncol 2021 Dec 10;39(35):3978-3992. Epub 2021 Nov 1 doi: 10.1200/JCO.21.01992. PMID: 34724386
Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma.
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M
Cochrane Database Syst Rev 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2. PMID: 34515338Free PMC Article
Cardiovascular Manifestations and Mechanisms in Patients with COVID-19.
Dou Q, Wei X, Zhou K, Yang S, Jia P
Trends Endocrinol Metab 2020 Dec;31(12):893-904. Epub 2020 Oct 16 doi: 10.1016/j.tem.2020.10.001. PMID: 33172748Free PMC Article
Interleukin-6 in Covid-19: A systematic review and meta-analysis.
Coomes EA, Haghbayan H
Rev Med Virol 2020 Nov;30(6):1-9. Epub 2020 Aug 26 doi: 10.1002/rmv.2141. PMID: 32845568Free PMC Article
Hematological findings and complications of COVID-19.
Terpos E, Ntanasis-Stathopoulos I, Elalamy I, Kastritis E, Sergentanis TN, Politou M, Psaltopoulou T, Gerotziafas G, Dimopoulos MA
Am J Hematol 2020 Jul;95(7):834-847. Epub 2020 May 23 doi: 10.1002/ajh.25829. PMID: 32282949Free PMC Article

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