Hemophagocytic lymphohistiocytosis in patients treated with immune checkpoint inhibitors: A pharmacovigilance study from FDA Database.

Abstract

e14684 Background: Immune checkpoint inhibitors (ICIs) are increasingly used to treat multiple cancers uncovering varieties of immune-related adverse events (irAEs). ICI-related haemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome caused by exaggerated activation of macrophages and cytotoxic T cells resulting in fatal hematological toxicity and multi-organ damage. Methods: We conducted a retrospective analysis of reported cases of HLH in patients treated with checkpoint inhibitors using data from the FDA's Adverse Event Reporting System (FAERS) database from 2018 to 2022. Patients aged 18 or older were included, and cases were classified using the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Results: Of 2,317 patients with HLH reported in the FAERS, 13.6% (315) of patients were reported to receive commonly used ICIs. With nivolumab being 44.93%%, pembrolizumab 35.87%, Ipilimumab 30.43%, and atezolizumab 15.94%. HLH among these ICI use was most commonly reported in males (65.2%) with a median age of 65. Melanoma was the most common cancer reported in this sample population. Out of the reported cases, 26% died, and 72% were males. Death was observed more in combination ICI therapy (40.73%) than in single-agent use (29.04%). Even though the most commonly reported HLH was with Nivolumab, mortality was highest with Atezolizumab use (29.55%). Conclusions: Nearly half of the patients with a diagnosis of HLH received commonly used ICIs, which points towards ICIs being one of the important risk factors for developing HLH. However, several confounders should be considered, like a cancer diagnosis, infection, and antibiotics. Further studies on ICI-induced HLH are necessary to establish its causal relationship.