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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

Revolutionizing cancer treatment: a comprehensive review of CAR-T cell therapy.
Dabas P, Danda A
Med Oncol 2023 Aug 22;40(9):275. doi: 10.1007/s12032-023-02146-y. PMID: 37608202
Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network.
Ludwig H, Terpos E, van de Donk N, Mateos MV, Moreau P, Dimopoulos MA, Delforge M, Rodriguez-Otero P, San-Miguel J, Yong K, Gay F, Einsele H, Mina R, Caers J, Driessen C, Musto P, Zweegman S, Engelhardt M, Cook G, Weisel K, Broijl A, Beksac M, Bila J, Schjesvold F, Cavo M, Hajek R, Touzeau C, Boccadoro M, Sonneveld P
Lancet Oncol 2023 Jun;24(6):e255-e269. doi: 10.1016/S1470-2045(23)00159-6. PMID: 37269857
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

Recent clinical studies

Etiology

CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up.
Müller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Völkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schäfer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Krönke G, Mackensen A, Schett G
N Engl J Med 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917. PMID: 38381673
Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer.
Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Bustamante Alvarez J, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L; DeLLphi-301 Investigators
N Engl J Med 2023 Nov 30;389(22):2063-2075. Epub 2023 Oct 20 doi: 10.1056/NEJMoa2307980. PMID: 37861218
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
Current concepts in the diagnosis and management of cytokine release syndrome.
Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL
Blood 2014 Jul 10;124(2):188-95. Epub 2014 May 29 doi: 10.1182/blood-2014-05-552729. PMID: 24876563Free 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
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
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
Current concepts in the diagnosis and management of cytokine release syndrome.
Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL
Blood 2014 Jul 10;124(2):188-95. Epub 2014 May 29 doi: 10.1182/blood-2014-05-552729. PMID: 24876563Free PMC Article

Therapy

Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer.
Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Bustamante Alvarez J, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L; DeLLphi-301 Investigators
N Engl J Med 2023 Nov 30;389(22):2063-2075. Epub 2023 Oct 20 doi: 10.1056/NEJMoa2307980. PMID: 37861218
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
CAR-T Cell Therapy in Hematological Malignancies: Current Opportunities and Challenges.
Zhang X, Zhu L, Zhang H, Chen S, Xiao Y
Front Immunol 2022;13:927153. Epub 2022 Jun 10 doi: 10.3389/fimmu.2022.927153. PMID: 35757715Free 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
Cytokine Release Syndrome with Chimeric Antigen Receptor T Cell Therapy.
Frey N, Porter D
Biol Blood Marrow Transplant 2019 Apr;25(4):e123-e127. Epub 2018 Dec 23 doi: 10.1016/j.bbmt.2018.12.756. PMID: 30586620

Prognosis

CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up.
Müller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Völkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schäfer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Krönke G, Mackensen A, Schett G
N Engl J Med 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917. PMID: 38381673
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
CD40 Agonist Antibodies in Cancer Immunotherapy.
Vonderheide RH
Annu Rev Med 2020 Jan 27;71:47-58. Epub 2019 Aug 14 doi: 10.1146/annurev-med-062518-045435. PMID: 31412220
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

CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up.
Müller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Völkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schäfer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Krönke G, Mackensen A, Schett G
N Engl J Med 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917. PMID: 38381673
From bench to bedside: the history and progress of CAR T cell therapy.
Mitra A, Barua A, Huang L, Ganguly S, Feng Q, He B
Front Immunol 2023;14:1188049. Epub 2023 May 15 doi: 10.3389/fimmu.2023.1188049. PMID: 37256141Free PMC Article
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
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
Current concepts in the diagnosis and management of cytokine release syndrome.
Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL
Blood 2014 Jul 10;124(2):188-95. Epub 2014 May 29 doi: 10.1182/blood-2014-05-552729. PMID: 24876563Free PMC Article

Recent systematic reviews

Toxicity and efficacy of CAR T-cell therapy in primary and secondary CNS lymphoma: a meta-analysis of 128 patients.
Cook MR, Dorris CS, Makambi KH, Luo Y, Munshi PN, Donato M, Rowley S, Saad A, Goy A, Dunleavy K, Ali A
Blood Adv 2023 Jan 10;7(1):32-39. doi: 10.1182/bloodadvances.2022008525. PMID: 36260735Free PMC Article
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
Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma.
Roex G, Timmers M, Wouters K, Campillo-Davo D, Flumens D, Schroyens W, Chu Y, Berneman ZN, Lion E, Luo F, Anguille S
J Hematol Oncol 2020 Dec 3;13(1):164. doi: 10.1186/s13045-020-01001-1. PMID: 33272302Free 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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