Clinical characteristics, treatment, and management of pembrolizumab induced hemophagocytic lymphohistiocytosis

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal adverse reaction to pembrolizumab. The clinical characteristics of pembrolizumab induced HLH are unknown. Exploring the clinical features of pembrolizumab induced HLH is crucial for the treatment and prevention of immune checkpoint inhibitor-induced HLH. Methods The literature related to pembrolizumab induced HLH was collected for retrospective analysis by searching the Chinese and English databases from inception until August 31, 2023. Results A total of 24 patients were included, including 17 men (70.8%) with a median age of 61 years (41,80). The time between the last infusion and the start of HLH ranged from 2 to 46 days, with a median time of 14 days. Fever (100%) was the most common symptom, accompanied by splenomegaly (14 cases, 58.3%) and hepatomegaly (6 cases, 25.0%). Laboratory examination revealed revealed anemia (18 cases, 75.0%), leukopenia (12 cases, 50.0%), thrombocytopenia (20 cases, 83.3%), hypertriglyceridemia (11 cases, 45.8%), hypofibrinogenemia (11 cases, 45.8%). decreased natural killer cell function (7 cases, 29.2%), and elevated soluble CD25(15 cases, 62.5%). All patients developed hyperferriinemia, with a median of 30,808 ng/mL (range 1303 similar to 100,000). Bone marrow biopsy showed hemophagocytosis (15 cases, 62.5%). After discontinuation of pembrolizumab and treatment with steroids, etoposide, intravenous immunoglobulin, cytokine blocking, and immunosuppression, 17 patients recovered or improved, and 5 patients eventually died. Conclusion HLH should be suspected when unexplained fever, cytopenia, splenomegaly, and elevated aminotransferase occur in patients using pembrolizumab. Screening for risk factors before treatment with pembrolizumab may be necessary to prevent HLH.

Automated summary

This study retrospectively analyzed the literature related to pembrolizumab-induced HLH. The results showed that the most common symptoms were fever, splenomegaly, and hepatomegaly. Laboratory examination revealed abnormalities in anemia, leukopenia, thrombocytopenia, hypertriglyceridemia, and hypofibrinogenemia. Bone marrow biopsy showed hemophagocytosis. After treatment with steroids, etoposide, intravenous immunoglobulin, cytokine blocking, and immunosuppression, the majority of patients showed improvement or recovery, but some patients still died.