Advances in PD-1 monoclonal antibody therapy for hemophagocytic syndrome

Hemophagocytic syndrome (HPS), also known as hemophagocytic lymphohistiocytosis (HLH), is a severe inflammatory condition, while the standard treatment still has limitations. With the conscious in-depth research on the pathogenesis, PD-1 (programmed cell death protein-1) monoclonal antibody has shown positive prospects in the treatment of HLH. This study retrospectively analyzed the clinical efficacy, and safety profile of PD-1 inhibitors in the treatment of HLH. A total of 15 studies was involved, covering with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and related malignancies. In pediatric patients with chronic active EBV infection (CAEBV) and refractory/relapsed EBV-HLH, sintilimab induced partial or complete clinical remission, and successfully served as a bridge therapy to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT). Retrospective studies on adult refractory/relapsed EBV-HLH showed that nivolumab treatment achieved an overall response rate (ORR) of 85.7% and a complete remission (CR) rate of 71.4% over 16 months. Sintilimab as salvage therapy also restored complete donor chimerism post-transplant and cleared viral loads. Furthermore, novel combinations with ruxolitinib, venetoclax, or thalidomide achieved rapid clinical remission in EBV-HLH. Safety assessments indicated that PD-1 blockade following HSCT was associated with a high risk of graft-versus-host disease (GVHD). Caution is warranted when using PD-1 monoclonal antibodies, as immune system stimulation is a double-edged sword. The optimal timing, dosage, and safety of PD-1 monoclonal antibodies in HLH treatment merit further clinical research and exploration.