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

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Abstract

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 ~ 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.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study was supported by the Natural Science Foundation of Hunan Province (No.2023JJ30847).

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Authors and Affiliations

  1. Department of Pharmacy, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, YueLu District, 410013, Changsha, Hunan, China

    Chunjiang Wang, Wei Sun, Zuojun Li, Tian Wu & Weijin Fang

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  4. Tian Wu
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Contributions

Chunjiang Wang and Weijin Fang: conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript; Wei Sun, Zuojun Li and Tian Wu: designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript; Zuojun Li and Tian Wu: coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content; all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Tian Wu or Weijin Fang.

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This study did not require an ethical board approval because the study was a retrospective study and did not involve sensitive personal information.

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Wang, C., Sun, W., Li, Z. et al. Clinical characteristics, treatment, and management of pembrolizumab induced hemophagocytic lymphohistiocytosis. Invest New Drugs 41, 834–841 (2023). https://doi.org/10.1007/s10637-023-01404-0

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