Immune checkpoint inhibitors (ICIs) have proven effective in the treatment of numerous cancers; however, they have been associated with immune-related adverse events (irAEs), among which cytokine release syndrome (CRS) has been reported in a few case reports. VigiBase database was analysed by researchers and details were published in frontiers pharmacology.
Immune checkpoint inhibitors (ICIs) have proven effective in the treatment of numerous cancers. By inhibiting negative regulators of the immune system, ICIs enhance immune activity against cancer cells and, aberrantly, against host non-cancer cells, resulting in inflammatory side effects also called immune-related adverse events (irAEs).
By hyper-activating the immune system to overcome the inhibitory signals of cancer cells, ICIs can provoke on-target autoimmune toxicity (when the targeted tumor antigen is on host non-cancer cells), as well as off-target cytokine-associated toxicity (also known as CRS).
Cytokine release syndrome (CRS) is a systemic inflammatory disease characterized by a massive release of cytokines. It can present with a variety of symptoms ranging from mild to life threatening, being sometimes fatal.
Mild symptoms of CRS include fever, fatigue, nausea, vomiting, headache, rash, arthralgia, myalgia, and malaise. In most severe cases, hypotension requiring high-dose vasopressors and hypoxia requiring mechanical ventilation may occur as life-threating complications.
Moreover, laboratory abnormalities that are common in patients with CRS include cytopenias, coagulopathy, elevated liver enzymes and creatinine, and high C reactive protein levels.
CRS can be triggered by infections or be associated with drugs such as monoclonal antibodies (e.g., rituximab), conventional chemotherapy, and immunotherapies with chimeric antigen receptor T (CAR T) cells.
“Despite the strict parallelism between ICI mechanism of action and CRS pathophysiologic mechanism, to date, only a few case reports have documented the association of ICIs as pharmacological triggers of CRS in cancer patients” says researchers.
The researchers gathered 80,700 safety reports of ICI-related ADRs, among which 58 concerned CRS from VigiBase. As per article beyond ICIs, co-suspected drugs were absent in a remarkable proportion of safety reports, suggesting that ICIs could contribute to CRS onset as pharmacological triggers.
Researchers say “Due to ICI expanding indications, clinicians should be aware that ICIs could contribute to CRS onset in cancer patients as pharmacological triggers. Further studies are needed to better characterize the mechanisms underlying ICI-related CRS.”
