Cytokine release syndrome

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The cytokine release syndrome , also known by the English term cytokine release syndrome ( CRS ) or macrophage activation syndrome, haemophagozytic lymphohistiocytosis , is an undesirable effect usually a chemotherapy , radiation therapy , CAR T cell therapy or rare when taking anti-inflammatory drugs .

It is considered an "infusion reaction" with flu-like symptoms, but can also be severe and fatal, which is why it represents an (oncological) emergency.

The term was coined in the 1950s as a rare genetic disease in children, at that time still under the name Haemophageocytische Lymphohistiocytose .

causes

Well-known triggers are CAR-T-cell therapy and the drugs rituximab , alemtuzumab , TGN1412 , antithymocyte globulin , basiliximab , interleukin-15 , lenalidomide , muromonab-CD3 and blinatumomab .

There is evidence of a mutation that resulted in flu deaths in the United States.

The activation of the T cells plays a role in the pathogenesis, so the CAR T cell therapy is an "on-target" effect. This releases large amounts of pro-inflammatory (proinflammatory) cytokines, especially interleukin-6 and interferon-γ .

Symptoms

In the case of mild symptoms, a flu-like clinical picture appears. Due to the increased release of cytokines (mostly due to the massive breakdown of cancer cells), symptoms such as fever , nausea , chills , arterial hypotension , tachycardia , asthenia , headache , rash and dyspnea exist in different degrees.

Massive reactions including cytokine storm occur frequently in the first treatment, especially in hematological malignant diseases can be life threatening and provide a oncologic emergency . It may be a hypoxia with ventilation need for a heavy Hpotension with reduced blood circulation in the extremities, a capillary leak syndrome ( capillary leak syndrome ) with edema formation of internal organs (especially pulmonary edema ) and finally multi-organ failure and disseminated intravascular coagulopathy .

In CAR-T-cell therapy, the occurrence of the syndrome correlates with the pharmacokinetics of the CAR-T-cells, the tumor cell load (number of blasts in the bone marrow puncture) and the response.

Classification

A strong expression is also known as a cytokine storm .

Based on the clinical course, the following degrees of severity can be differentiated retrospectively:

  • Grade 1 (only symptomatic therapy required)
  • Grade 2 (moderately intensive treatment necessary)
  • Grade 3 (aggressive therapy necessary)
  • Grade 4 (life threatening)
  • Grade 5 (resulting in death)

therapy

Antihistamines , cortisone or NSAIDs can be given preventively in rheumatic diseases .

The antibody tocilizumab , which is directed against interleukin-6 , was approved for the treatment of CRS in 2017 and is the standard therapy in CAR T-cell therapy if the response is very good.

literature

  • D. Porter, N. Frey, PA Wood, Y. Weng, SA Grupp: Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. In: Journal of hematology & oncology. Vol. 11, No. 1, March 2018, p. 35, doi: 10.1186 / s13045-018-0571-y , PMID 29499750 , PMC 5833070 (free full text) (review).
  • Z. Wang, W. Han: Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy. In: Biomarker research. Vol. 6, 2018, p. 4, doi: 10.1186 / s40364-018-0116-0 , PMID 29387417 , PMC 5778792 (free full text) (review).
  • JT Denny, AT Burr, F. Balzer, JT Tse, JE Denny, D. Chyu: Methylene blue treatment for cytokine release syndrome-associated vasoplegia following a renal transplant with rATG infusion: A case report and literature review. In: Experimental and therapeutic medicine. Vol. 9, No. 5, May 2015, pp. 1915–1920, doi: 10.3892 / etm.2015.2349 , PMID 26136914 , PMC 4471690 (free full text).
  • SL Maude, D. Barrett, DT Teachey, SA Grupp: Managing cytokine release syndrome associated with novel T cell-engaging therapies. In: Cancer journal. Vol. 20, No. 2, 2014 Mar – Apr, pp. 119–122, doi: 10.1097 / PPO.0000000000000035 , PMID 24667956 , PMC 4119809 (free full text) (review).
  • K. Makino, J. Nakata, S. Kawachi, T. Hayashi, A. Nakajima, M. Yokoyama: Treatment strategy for reducing the risk of rituximab-induced cytokine release syndrome in patients with intravascular large B-cell lymphoma: a case report and review of the literature. In: Journal of medical case reports. Vol. 7, December 2013, p. 280, doi: 10.1186 / 1752-1947-7-280 , PMID 24377366 , PMC 3923559 (free full text).

Individual evidence

  1. ↑ a b c Matt Windsor: There's a playbook for stopping deadly cytokine storm syndrome. In: UAB. University of Alabama at Birmingham, November 1, 2019, accessed April 2, 2020 .
  2. ↑ a b D. W. Lee, R. Gardner, DL Porter, CU Louis, N. Ahmed, M. Jensen, SA Grupp, CL Mackall: Current concepts in the diagnosis and management of cytokine release syndrome. In: Blood. Vol. 124, No. 2, July 2014, pp. 188-195, doi: 10.1182 / blood-2014-05-552729 , PMID 24876563 , PMC 4093680 (free full text).
  3. ↑ CA Barker, SK Kim, S. Budhu, K. Matsoukas, AF Daniyan, SP D'Angelo: Cytokine release syndrome after radiation therapy: case report and review of the literature. In: Journal for immunotherapy of cancer. Vol. 6, No. 1, January 2018, p. 1, doi: 10.1186 / s40425-017-0311-9 , PMID 29298730 , PMC 5795275 (free full text).
  4. ↑ SL Maude, D. Barrett et al. a .: Managing cytokine release syndrome associated with novel T cell-engaging therapies. In: Cancer journal. Volume 20, number 2, 2014 Mar-Apr, pp. 119-122, doi: 10.1097 / PPO.0000000000000035 , PMID 24667956 , PMC 4119809 (free full text) (review).
  5. ↑ Angela Krackhart: Immunotherapy against cancer. Munich medical advertisements, March 27, 2020, accessed on April 2, 2020 .
  6. ↑ Roche Red Hand Letter on August 5, 2011 .
  7. ^ CAR T Cells: Engineering Patients' Immune Cells to Treat Their Cancers
  8. ↑ HS Kulkarni, PM Kasi: Rituximab and cytokine release syndrome. In: Case reports in oncology. Vol. 5, No. 1, January 2012, pp. 134–141, doi: 10.1159 / 000337577 , PMID 22666201 , PMC 3364040 (free full text)
  9. ↑ LC Lim, LP Koh, P. Tan: Fatal cytokine release syndrome with chimeric anti-CD20 monoclonal antibody rituximab in a 71-year-old patient with chronic lymphocytic leukemia. In: Journal of clinical oncology: official journal of the American Society of Clinical Oncology. Vol. 17, No. 6, June 1999, pp. 1962-1963, doi: 10.1200 / jco.1999 , June 17, 1962 , PMID 10561242 .
  10. ↑ S. Cooley, F. He et al. a .: First-in-human trial of rhIL-15 and haploidentical natural killer cell therapy for advanced acute myeloid leukemia. In: Blood Advances. Volume 3, number 13, July 2019, pp. 1970–1980, doi: 10.1182 / bloodadvances.2018028332 , PMID 31266741 , PMC 6616260 (free full text).
  11. ^ MD Nexus
  12. ^ NV Frey, DL Porter: Cytokine release syndrome with novel therapeutics for acute lymphoblastic leukemia. In: Hematology. American Society of Hematology. Education Program. Volume 2016, number 1, December 2016, pp. 567-572, doi: 10.1182 / asheducation-2016.1.567 , PMID 27913530 , PMC 6142489 (free full text) (review).
  13. ^ S. Breslin: Cytokine-release syndrome: overview and nursing implications. In: Clinical journal of oncology nursing. Vol. 11, No. 1 Suppl, February 2007, pp. 37-42, doi: 10.1188 / 07.CJON.S1.37-42 , PMID 17471824 (review).
  14. ↑ Carl H. June, Michel Sadelain: Chimeric Antigen Receptor Therapy New England Journal of Medicine 2018, Volume 379, Issue 1 of July 5, 2018, pages 64-73, DOI: 10.1056 / NEJMra1706169
  15. ↑ Roche press release

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