Treatment of pediatric refractory or relapsed Epstein–Barr virus‐associated hemophagocytic syndrome with PD‐1 inhibitors

Abstract Purpose Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis (EBV‐HLH) is a type of pediatric HLH that occurs frequently in Asia. Although immunochemotherapy based on etoposide and hormone has improved survival rates, there are still about 30% of HLH patients that do not respond. The objective of the article is to examine the efficacy and safety of programmed cell death protein 1 (PD‐1) inhibitors for children with relapsed/refractory (r/r) EBV‐HLH. Methods A retrospective case note review of four pediatric patients with r/r EBV‐HLH who were treated with PD‐1 inhibitors at Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University. Results All four patients responded to PD‐1 inhibitors and achieved partial response after their first infusion. Plasma EBV DNA copy number and HLH‐related monitoring indicators decreased in all of these patients. All patients received allogeneic hematopoietic stem cell transplantation (allo‐HSCT), and two were still alive at the last follow‐up on December 30, 2022. Two patients died because of transplantation‐related complications. Serious side effects included increased liver enzymes and edema in two patients. Conclusion PD‐1 inhibitors are an effective salvage therapy and can provide a bridge to allo‐HSCT for pediatric patients with r/r EBV‐HLH. However, side effects should be monitered.