Immunological analysis of the murine anti‐CD3‐induced cytokine release syndrome model and therapeutic efficacy of anti‐cytokine antibodies

Background: Tocilizumab is an interleukin-6 receptor antagonist hypothesized to blunt the uncontrolled immune response, cytokine release syndrome, in severe COVID-19 and prevent attributable morbidity and mortality. Objective: The objective of this study was to assess the impact of tocilizumab on clinical outcomes in COVID-19-associated cytokine release syndrome. Methods: Single-center, retrospective cohort study assessing sixty-nine adult patients receiving tocilizumab for suspected COVID-19 cytokine release syndrome. The primary outcome was change in WHO clinical status scale on day seven post-dose analyzed using the Wilcoxon signed rank test. Secondary outcomes assessed impact of timing of administration on clinical outcome. Safety analyses included development of neutropenia, thrombocytopenia, transaminitis, and sepsis within 7 days post-dose. Statistical analyses were conducted using Microsoft Excel. Results: No aggregate clinical change was found between day 0 and day 7. Eleven patients improved, twenty-seven worsened, and thirty-one showed no change. Clinical outcomes were weakly correlated with time from symptom onset (rs = 0.21; p = 0.08) or hospital admission (rs = -0.08; p = 0.49) to dose. In-hospital mortality was 63%. Sepsis was diagnosed in 21 patients, five of which were post-dose. Transaminitis, neutropenia, and thrombocytopenia occurred in seven, one, and six patients, respectively. Conclusion: Tocilizumab did not appear to influence clinical outcomes in our study population, irrespective of timing of administration. Adverse events were not considered drug-related.

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Nichts für Schönwetterkapitäne: CAR-T-Zellen – Immunonkologie trifft Intensivmedizin

TumorDiagnostik & Therapie ◽

10.1055/a-1294-7270 ◽

2020 ◽

Vol 41 (10) ◽

pp. 673-679

Author(s):

Jorge Garcia Borrega ◽

Michael von Bergwelt-Baildon ◽

Boris Böll

Keyword(s):

Real World ◽

Effector Cell ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Immune Effector Cell ◽

Immune Effector ◽

Car T

Zusammenfassung CRS und ICANS als Nebenwirkung von CAR-T-Zellen Das Cytokine-Release-Syndrome (CRS) ist die häufigste Nebenwirkung einer CAR-T-Zell-Therapie und kann von leichtem Fieber bis zu einem Multiorganversagen führen. Pathophysiologisch kommt es beim CRS zu einem Zytokinsturm und trotz einer Therapie mit Tocilizumab sind refraktäre und tödliche Verläufe beschrieben. Die Symptome des Immune-Effector-Cell-associated-Neurotoxicity-Syndrome (ICANS) variieren von leichter Desorientiertheit bis zum lebensbedrohlichen Hirnödem. Die Pathophysiologie und Therapie des ICANS sind noch nicht ausreichend erforscht. Die Differenzialdiagnosen von CRS und ICANS sind komplex und umfassen neben Infektionen und Sepsis unter anderem auch eine Toxizität der vorhergehenden Therapie, ein Tumorlysesyndrom und nicht zuletzt einen Progress der Grunderkrankung. Ein klinischer oder laborchemischer Parameter zum sicheren Beweis oder Ausschluss eines CRS oder ICANS gibt es zum heutigen Zeitpunkt nicht. Intensivmedizinische Relevanz und potenzielle Entwicklungen der CAR-T-Zell-Therapie Erste Auswertungen von Real-world-Daten deuten auf eine höhere Rate an schweren Nebenwirkungen im Rahmen der CAR-T-Zell-Therapie als in den Zulassungsstudien hin. Für die Indikation r/r-DLBCL könnten schätzungsweise bis zu maximal 300 Patienten pro Jahr in Deutschland eine intensivmedizinische Betreuung im Rahmen der CAR-T-Zell-Therapie benötigen. Studien mit wesentlich häufigeren soliden Tumoren könnten die Patientenzahl drastisch erhöhen. Therapieziel bei CAR-T-Zell-Patienten und Entscheidungen bei Therapiezieländerung Aufgrund des neuen Therapiekonzepts kann ein Konflikt zwischen bislang palliativem Patientenkollektiv und nun möglicherweise langfristigen Remissionen entstehen. Eine frühzeitige Aufklärung über potenziell lebensbedrohliche Nebenwirkungen im Rahmen der Therapie und eine interdisziplinäre Besprechung der Therapieziele mit den Patienten ist entscheidend.

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“Tocilizumab-an option for patients with COVID-19 associated cytokine release syndrome: A single center experience”, a retrospective study-original article

Annals of Medicine and Surgery ◽

10.1016/j.amsu.2021.02.011 ◽

2021 ◽

Vol 63 ◽

pp. 102165

Author(s):

Aijaz Zeeshan Khan Chachar ◽

Khurshid Ahmed Khan ◽

Javeid Iqbal ◽

Adnan Hussain Shahid ◽

Mohsin Asif ◽

...

Keyword(s):

Retrospective Study ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Single Center ◽

Single Center Experience

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Macrophage Activation and Cytokine Release Syndrome in COVID-19: Current Updates and Analysis of Repurposed and Investigational Anti-Cytokine Drugs

Drug Research ◽

10.1055/a-1291-7692 ◽

2021 ◽

Cited By ~ 1

Author(s):

Ashif Iqubal ◽

Farazul Hoda ◽

Abul Kalam Najmi ◽

Syed Ehtaishamul Haque

Keyword(s):

Immune Response ◽

Clinical Trials ◽

Macrophage Activation ◽

Fatality Rate ◽

Cytokine Storm ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Disease Condition ◽

Inflammatory Drugs ◽

Anti Inflammatory

AbstractCoronavirus disease (COVID-19) emerged from Wuhan, has now become pandemic and the mortality rate is growing exponentially. Clinical complication and fatality rate is much higher for patients having co-morbid issues. Compromised immune response and hyper inflammation is hall mark of pathogenesis and major cause of mortality. Cytokine release syndrome (CRS) or cytokine storm is a term used to affiliate the situation of hyper inflammation and therefore use of anti-cytokine and anti-inflammatory drugs is used to take care of this situation. Looking into the clinical benefit of these anti-inflammatory drugs, many of them enter into clinical trials. However, understanding the immunopathology of COVID-19 is important otherwise, indiscriminate use of these drugs could be fetal as there exists a very fine line of difference between viral clearing cytokines and inflammatory cytokines. If any drug suppresses the viral clearing cytokines, it will worsen the situation and hence, the use of these drugs must be based on the clinical condition, viral load, co-existing disease condition and severity of the infection.

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Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2

Nature Medicine ◽

10.1038/s41591-021-01387-6 ◽

2021 ◽

Author(s):

Lewis Au ◽

◽

Annika Fendler ◽

Scott T. C. Shepherd ◽

Karolina Rzeniewicz ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Checkpoint Inhibitors ◽

Temporal Association ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Vaccination Programs ◽

Patients With Cancer ◽

Related Adverse Event ◽

Pd1 Blockade

AbstractPatients with cancer are currently prioritized in coronavirus disease 2019 (COVID-19) vaccination programs globally, which includes administration of mRNA vaccines. Cytokine release syndrome (CRS) has not been reported with mRNA vaccines and is an extremely rare immune-related adverse event of immune checkpoint inhibitors. We present a case of CRS that occurred 5 d after vaccination with BTN162b2 (tozinameran)—the Pfizer-BioNTech mRNA COVID-19 vaccine—in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-γ/IL-2R/IL-18/IL-16/IL-10) and steroid responsiveness. The close temporal association of vaccination and diagnosis of CRS in this case suggests that CRS was a vaccine-related adverse event; with anti-PD1 blockade as a potential contributor. Overall, further prospective pharmacovigillence data are needed in patients with cancer, but the benefit–risk profile remains strongly in favor of COVID-19 vaccination in this population.

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Rituximab induced cytokine release syndrome in an MS patient: A case report

Clinical Case Reports ◽

10.1002/ccr3.4407 ◽

2021 ◽

Vol 9 (7) ◽

Author(s):

Masoud Etemadifar ◽

Mehri Salari ◽

Mahdieh Saeri ◽

Amirhossein Akhavan Sigari ◽

Sara Ebrahimi Pelarti

Keyword(s):

Case Report ◽

Cytokine Release ◽

Cytokine Release Syndrome

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