Clinical characterization of hemophagocytic lymphohistiocytosis caused by immune checkpoint inhibitors: a review of published cases

ABSTRACT

Objective:

An association exists between immune checkpoint inhibitors and hemophagocytic lymphohistiocytosis (HLH). Therefore, the main objective of this study was to collect data on this rare but potentially life-threatening immune-related adverse reaction to identify the medications that cause it, the clinical characteristics, and effective treatments.

Methods:

Literature in English and Chinese on immune checkpoint inhibitors causing HLH published from August 2014 to March 2024 was analyzed. Immune checkpoint inhibitors, immunotherapy, anti-PD-1, PD-L1 inhibitors, HLH, hemophagocytic lymphohistiocytosis, hemophagocytic syndrome keywords were used to find the literature on China Knowledge Network, Wanfang, PubMed and Emabase Databases.

Results and discussion:

Twenty-four studies were included, with a total of 27 patients (18 males and 9 females) with a mean age of 58 years (range 26–86). The mean time to the onset of symptoms was 10.3 weeks (7 days–14 months). The main clinical characteristics were fever, cytopenia, splenomegaly, methemoglobinemia, hypofibrinogenemia, and bone marrow biopsy showed phagocytosis. Twenty-two patients improved after the treatment with steroids, cytokine blocking therapy and symptomatic treatment, four patients died, and one patient was not described.

Conclusion:

HLH should be not underestimated as a potentially serious adverse effect of immune checkpoint inhibitors since appropriate treatments may save the life of patients.

KEYWORDS:

• Immune checkpoint inhibitors
• haemophagocytic lymphohistiocytosis
• clinical characteristic
• immune-related adverse effects
• ‌HLH
• Hscore
• Hemophagocytosis
• irAEs

Acknowledgements

The authors thank all people who contributed to this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Conflicts of interest

Zhiya Xu – has no relevant conflicts of interest.

Huilan Li – has no relevant conflicts of interest.

Xinyi Yu – has no relevant conflicts of interest.

Jia Luo – has no relevant conflicts of interest.

Zanling Zhang – has no relevant conflicts of interest.

Data availability statement

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

Conflicts of interest

All authors declare no competing interests.