AA amyloidosis as an adverse event of immune checkpoint inhibitor therapy: evidence from the FDA adverse event reporting system and a systematic review

Abstract

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are linked to immune-related adverse events (irAEs). Secondary (AA) amyloidosis, an inflammatory complication involving serum amyloid A deposition, has been sporadically reported in ICI-treated patients. We investigated the link between ICI therapy and AA amyloidosis using pharmacovigilance data and a systematic review. Methods: We conducted a disproportionality analysis of FDA adverse event reporting system (FAERS) data (January 2015–June 2024), selecting amyloidosis-related cases using MedDRA preferred terms. Signal detection employed reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean. We also reviewed published cases from six databases (searched 30 November 2024). Studies reporting AA amyloidosis linked to ICI use were included, and the risk of bias was assessed using the Joanna Briggs Institute tools. Results were summarised descriptively (PROSPERO ID: CRD42024622091). Results: Among 13,209,688 unique FAERS reports, 26 relevant cases were identified. Patients were mainly older adults (median age 71.5 years), with serious outcomes including death (19.2%) and hospitalisation (30.8%). Disproportionality analyses showed a significant link, and the systematic review included 11 cases, primarily renal, with poor outcomes despite treatment. Conclusion: Findings support AA amyloidosis as a rare but serious irAE of ICI therapy, warranting further investigation. © 2025 Informa UK Limited, trading as Taylor & Francis Group.