Immune checkpoint inhibitors-related cytokine storm syndrome: a systematic review of characteristics, treatment, and outcomes

Abstract

Objective To analyze and summarize the general patterns and key points of treatment for cytokine release syndrome (CRS) induced by immune checkpoint inhibitors (ICIs), and provide references for the differential diagnosis and treatment of this immune-related adverse event (irAE) and the safe application of ICIs. Methods Case reports published in domestic and international databases were collected. Basic information of patients and CRS were extracted from the included cases to clarify the characteristics and intervention measures of this irAE. Results A total of 58 articles involving 59 patients were finally included, comprising 36 males and 23 females. The average age of the included patients was (58.54 ± 15.29) years, and lung cancer was the most common primary disease. Ten types of ICIs were used during treatment, and CRS occurred within the first four cycles of ICI administration in the vast majority of patients. Abnormal biochemical and inflammatory indicators could contribute to the diagnosis and confirmation of CRS, while the initial clinical manifestations of included patients were mostly non-specific, with about half of them experiencing at least one other concurrent irAE. With active treatment, 50 patients had a good outcome, but 9 patients died. Conclusion CRS induced by ICIs is a rare but severe irAE. Risk factor assessment and patient education should be conducted before initiating ICIs therapy. If symptoms such as fever and hypotension occur during treatment, accompanied by abnormalities in characteristic indicators like C-reactive protein and related cytokines, individualized treatment should be implemented as early as possible to ensure the safe administration of ICIs.