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

Abstract

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 rechallenge with ICIs after mild CRS was generally safe. However, two out of 28 patients experienced high-grade CRS, and one was fatal. While C-reactive protein (CRP) 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.

Keywords: Cytokine release syndrome; immune checkpoint inhibitors; immune-related adverse events.

Figure 1.

Assessment of qSOFA and laboratory tests at time of admission for cytokine release syndrome (CRS) in patients receiving immune checkpoint inhibition treatment. (a) qSOFA score associated with CRS grade, n = 28. (b) Level of CRP associated with CRS grade, n = 28. (c) procalcitonin level associated with CRS grade, n = 19. (d) Neutrophile count associated with CRS grade, n = 28. (e) Leukocyte count associated with CRS grade, n = 28. qSOFA: quick Sequential Organ Failure Assessment, CRP: C-reactive protein.