Immune checkpoint inhibitor rechallenge after immune-related adverse events: a retrospective study from VigiBase update in 2024 looking for emergent safety signals

OBJECTIVES: Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after occurrence of an immune-related adverse event (irAE). We aim to identify potential emergent safety signals. DESIGN: This is an update of our observational pharmacovigilance cohort study. SETTING: We exanimated individual case safety reports from the WHO database VigiBase. PARTICIPANTS: We included all individual case safety reports with ICI and rechallenged ICI. INTERVENTIONS: We identified that incident irAE cases using the Medical Dictionary for Regulatory Activities V.26.1 related with at least one ICI administration were systematically collected until 1 March 2024. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the recurrence rate (expressed as a percentage with its 95% CI) of the initial irAE postrechallenge with the same ICI. RESULTS: We identified 1016 irAEs cases from ICI rechallenges. Of these, 323 irAEs recurrences occurred (31.8%, 95% CI 28.1 to 34.0). The most common postrechallenge irAEs were nephritis (recurrence rate: 50%, 95% CI 25 to 75), skin irAEs (44%, 95% CI 31 to 58) and colitis (39%, 95% CI 33 to 44). CONCLUSIONS: In this updated, largest cohort study on rechallenge (NCT04696250), we observed a 31.8% recurrence rate of the same irAE postrechallenge with the same ICI, building on our previous findings. TRIAL REGISTRATION NUMBER: NCT04696250.