Ipilimumab, nivolumab

Potential risk of hemophagocytic lymphohistiocytosis (HLH)

Canada. Health Canada will work with the manufacturers of ipilimumab and nivolumab to determine appropriate label changes to the product safety information to include the potential risk of hemophagocytic lymphohistiocytosis (HLH). 

HLH is a condition where large numbers of immune cells destroy other blood cells.

Ipilimumab and nivolumab are indicated to treat different types of cancers, including cancers of the skin, kidney, lung and liver.

Health Canada conducted a safety review of the risk of HLH associated with the use of ipilimumab or nivolumab following reports of HLH published in medical literature.

Health Canada has received one Canadian report of a cancer patient who developed HLH after treatment with nivolumab in combination with ipilimumab. The report was considered serious and resulted in death. Additionally, Health Canada reviewed 21 international reports of HLH following treatment with nivolumab and ipilimumab, either used alone or in combination. All reports were considered serious, and six of 21 cases were fatal. However, Health Canada could not confirm a causal relationship between the medicines and death in these cases. The medical literature suggests a potential link between the use of the medicines and the development of HLH.

Reference: Summary Safety Review, Health Canada, 24 June 2019 (hc-sc.gc.ca) (See WHO Pharmaceuticals Newsletter No.2, 2019 : Risk of serious blood disorder in Japan)