Immune checkpoint inhibitor-induced pure red cell aplasia: Case series and large-scale pharmacovigilance analysis

Introduction: Impressive advances in immunotherapy, especially immune checkpoint inhibitors (ICIs), have made great progress in treating multiple cancers. However, ICIs can also cause serious, even incurable, immune-related adverse events (irAEs), most often in patients with colitis, dermatitis, hepatitis, and thyroiditis. Rare autoimmune hematologic toxicities have been reported in the literature but are poorly described. Pure red cell aplasia (PRCA) induced by ICIs is a life-threatening autoimmune disease; however, only a few cases have been reported in the literature.Objective: To characterize and evaluate PRCA associated with different ICI regimens in a public database and to review the relevant literature.Methods: We described a case series of patients experiencing PRCA while on ICIs. We also mined the Food and Drug Administration's Adverse Event Reporting System (FAERS) and used reporting odds ratio (ROR), propor-tional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze the data of the suspected adverse events of PRCA induced by ICIs between January 2011 and June 2022.Results: Fifteen patients with PRCA events while on ICIs were included in our case series. In FAERS, a total of 41 individual case safety reports (ICSRs) with different ICI regimens were retrieved, among which 28 (68.3%) were related to monotherapy and three (7.3%) involved a fatal outcome. Signals of PRCA for all four ICI mono -therapies (nivolumab, pembrolizumab, durvalumab, and atezolizumab) and ICI combination therapy (ipilimu-mab/nivolumab) were detected. Ipilimumab/nivolumab presented a higher reporting signal than nivolumab. Conclusions: There is a significant reporting signal of PRCA with several ICI agents. Clinicians should be aware of and monitor this potentially fatal adverse event.