SHM's Clinical Quick Talks-Cytokine Release Syndrome

Pdf Summary

Cytokine Release Syndrome (CRS) is a significant clinical condition often observed as a side effect of immune effector cell (IEC) therapies like CAR T-cell therapy and bispecific T-cell engager therapies. The American Society for Transplantation and Cellular Therapy (ASTCT) defines CRS as an overactive immune response marked initially by fever and potential symptoms like hypotension, capillary leak causing hypoxia, and organ dysfunction. Aside from treatment-based CRS, conditions like severe COVID-19 can trigger a similar cytokine release, termed a "cytokine storm," necessitating different management approaches due to its infectious origin.<br /><br />The pathophysiology of CRS involves the release of cytokines such as IFN-g, IL-6, TNF-a, and IL-10 from activated immune cells and subsequent activation of endothelial cells. CRS typically manifests within 14 days of commencing IEC therapy. Symptoms include fever, hypotension, hypoxia, and other systemic signs, including chills, headache, and rash.<br /><br />CRS is graded based on symptom severity, with management strategies tailored accordingly. Mild cases (Grade 1) involve fever management with acetaminophen and possibly dexamethasone. Grades 2 to 4 involve additional interventions, such as tocilizumab, corticosteroids, ICU admission, and supplemental oxygen, depending on the severity of hypotension and hypoxia.<br /><br />Accurate diagnosis is crucial, distinguishing CRS from conditions such as sepsis, due to differing treatments. Core CRS management strategies include corticosteroids, tocilizumab, acetaminophen, and supportive therapies like broad-spectrum antibiotics and hemodynamic support. Neurotoxicity, though potentially concurrent, is managed separately under the criteria for Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).<br /><br />CRS presents as a clinical diagnosis, not reliant on laboratory parameters, and requires rapid management to prevent complications. This summary reflects the most recent guidelines as of December 2024.

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Christopher Pope, Michael Brister

Keywords

Cytokine Release Syndrome

CRS

immune effector cell therapies

CAR T-cell therapy

cytokine storm

ASTCT

tocilizumab

ICANS

neurotoxicity

pathophysiology