BACKGROUND: Acquired hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal condition characterized by hyperactivation of macrophages and cytotoxic lymphocytes, combining a series of non-specific clinical symptoms and laboratory disorders.
Etiologies are multiple: infectious (mainly viral) but also oncologic, autoimmune or drug-induced. Immune checkpoint inhibitors (ICI) are recent anti-tumor agents associated with a novel profile of adverse events triggered by immune system over-activation. Here, we sought to provide a comprehensive description and analysis of HLH cases reported with ICI since 2014.
METHODS: Disproportionality analyses were performed in order to further explore the association between ICI therapy and HLH. We selected 190 cases, 177 from the World Health Organization pharmacovigilance database and 13 from the literature. Detailed clinical characteristics were retrieved from the literature and from the French pharmacovigilance database.
RESULTS: The cases of HLH reported with ICI concerned men in 65% of cases with a median age of 64 years. HLH occurred in an average of 102 days after the initiation of ICI treatment and mostly concerned nivolumab, pembrolizumab and nivolumab/ipilimumab combination. All cases were considered serious. Most cases presented a favorable outcome (58.4%); however, death was reported for 15.3% of patients. Disproportionality analyses showed that HLH was seven times more frequently reported with ICI therapy than with other drugs and three times more than with other antineoplastic agents.
CONCLUSIONS: Clinicians should be aware of the potential risk of ICI-related HLH to improve the early diagnosis of this rare immune-related adverse event.
|ジャーナル名||Journal of clinical medicine|
|投稿者||Diaz, Laurine; Jauzelon, Benjamin; Dillies, Anne-Charlotte; Le Souder, Cosette; Faillie, Jean-Luc; Maria, Alexandre Thibault Jacques; Palassin, Pascale|
|組織名||Department of Medical Pharmacology and Toxicology, CHU Montpellier, Montpellier;University, 34000 Montpellier, France.;Internal Medicine & Immuno-Oncology (MedI2O), CHU Montpellier, 34000 Montpellier,;France.;Desbrest Institute of Epidemiology and Public Health (IDESP), Montpellier;University, INSERM, 34000 Montpellier, France.;Institute for Regenerative Medicine and Biotherapy (IRMB), Montpellier|