Cytokine release syndrome after treatment with immune checkpoint inhibitors: an observational cohort study of 2672 patients from Karolinska University Hospital in Sweden

Immune checkpoint inhibitors (ICIs) are linked to diverse immune-related adverse events (irAEs). Rare irAEs surface first in clinical practice. Here, we systematically studied the rare irAE, cytokine-release syndrome (CRS), in a cohort of 2672 patients treated with ICIs at Karolinska University Hospital in Stockholm, Sweden. We find that the risk of ICI-induced CRS – defined as fever, negative microbiological findings and absence of other probable causes within 30 days after ICI treatment – is approximately 1%, higher than previously reported. ICI-induced CRS was often mild and ICI rechallenge was generally safe. Two out of 28 patients experienced high-grade CRS, and one was fatal. While C-reactive protein and procalcitonin were not discriminative of fatal CRS, our data suggest that the quick Sequential Organ Failure Assessment (qSOFA) score might identify high-risk patients. These data provide a framework for CRS risk assessment and motivate multicenter studies to improve early CRS diagnosis. Highlights Cytokine release syndrome following immune checkpoint inhibition is rare and often mild. Risk assessment using quick Sequential Organ Failure Assessment, but not serum CRP, can potentially detect severe cytokine release syndrome and improve treatment decisions. Rechallenge with immune checkpoint inhibitors after mild cytokine release syndrome is generally well tolerated.