Delayed and multisystem immune-related adverse events in MSI-high colon cancer treated with nivolumab plus ipilimumab

Abstract Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) involving multiple organs. However, delayed-onset, multisystem irAEs after treatment discontinuation are uncommon. Here, we present a rare case of a man in his 50s with microsatellite instability-high colon cancer who developed multisystem irAEs following treatment with nivolumab plus ipilimumab. The patient developed adrenocorticotropic hormone deficiency after four cycles of combination therapy, which improved with hydrocortisone supplementation. Following eight cycles of nivolumab monotherapy, treatment was discontinued because no cancerous lesions were detected. Six months after the final nivolumab administration, the patient presented with bilateral knee arthritis and elevated hepatobiliary and pancreatic enzyme levels. No evidence of infectious, autoimmune, or IgG4-related disease was found. Liver biopsy revealed portal lymphocytic infiltration with a predominance of CD8-positive cells. The patient was diagnosed with delayed ICI-related arthritis, accompanied by asymptomatic cholangitis and pancreatitis. These irAEs improved rapidly after prednisolone administration. This case demonstrates that irAEs can occur in a delayed and multisystem manner, even after the cessation of ICIs. Thus, clinicians should consider irAEs in the differential diagnosis when new symptoms or unexplained laboratory abnormalities occur in patients with prior ICI exposure.