Haemophagocytic Lymphohistiocytosis Following Ipilimumab and Nivolumab in Malignant Pleural Mesothelioma: A Case Report

Our plain-English summary of Haemophagocytic Lymphohistiocytosis Following Ipilimumab and Nivolumab in Malignant Pleural Mesothelioma: A Case Report, by C.M. Than, M. Moe, Y. Win, et al (Curēus, 2026).

The study

• Authors: C.M. Than, M. Moe, Y. Win, K. Maung
• Journal: Curēus
• Published: 2026;18(7):e112768
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

Haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal hyperinflammatory syndrome caused by dysregulated immune activation. With the increasing use of immune checkpoint inhibitors (ICIs), HLH has emerged as an uncommon but serious immune-related adverse event. An 84-year-old woman with malignant pleural mesothelioma developed fever, rigours, collapse, confusion, worsening cytopenias, cholestatic liver dysfunction, marked hyperferritinaemia, hypertriglyceridaemia, and hypofibrinogenaemia after treatment with ipilimumab and nivolumab. Extensive microbiological investigations were negative. She fulfilled five HLH-2004 diagnostic criteria, supporting a diagnosis of probable ICI-associated HLH. Dexamethasone was started, with rapid clinical and biochemical improvement. This case highlights the importance of recognising HLH as a rare but life-threatening complication of checkpoint inhibitor therapy and supports early corticosteroid treatment, once infection has been reasonably excluded.

Copyright © 2026, Than et al.

In plain English

This was a case report of an 84-year-old woman with malignant pleural mesothelioma treated with the immunotherapy drugs ipilimumab and nivolumab. The report did not discuss asbestos exposure. She was admitted with fever, rigours and collapse, later became confused, and a scan showed a lung blood clot (pulmonary embolism). Despite antibiotics for presumed infection, her fever persisted and blood counts and liver tests worsened. Tests for infection were negative. Before steroids her ferritin was above 15,000 μg/L, triglycerides 3.36 mmol/L and fibrinogen 1.2 g/L. The authors counted five of eight HLH-2004 criteria, but their introduction treats high triglycerides and low fibrinogen as one criterion, making four. They diagnosed probable haemophagocytic lymphohistiocytosis (HLH), a severe overactive immune reaction, linked to the immunotherapy. Some criteria could not be shown or tested. The immunotherapy was withheld and she received the steroid dexamethasone. Her fever resolved, her mental state normalised, and she went home on day 10. The authors concluded that HLH is a rare but potentially life-threatening complication of immunotherapy and that prompt steroids, once infection has been reasonably excluded, may bring rapid improvement.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (single patient)
• Who was studied: one 84-year-old woman with malignant pleural mesothelioma receiving ipilimumab and nivolumab; location and dates of care not stated
• Exposure: treatment with the immune checkpoint inhibitors ipilimumab and nivolumab (dual checkpoint inhibition); no asbestos exposure is described
• Main results:
  • CT pulmonary angiography showed an acute segmental pulmonary embolism in the right upper lobe
  • Despite antibiotics, the patient remained febrile with worsening cytopenias and progressive cholestatic liver dysfunction
  • Before dexamethasone, the patient's ferritin was greater than 15,000 μg/L (reference 15-150 μg/L)
  • Before dexamethasone, the patient's triglycerides were 3.36 mmol/L (reference below 1.7 mmol/L)
  • Before dexamethasone, the patient's fibrinogen was 1.2 g/L (reference 2.0-4.0 g/L)
  • The authors reported that the patient met five of the eight HLH-2004 criteria, counting fever, cytopenias in at least two cell lines, hypertriglyceridaemia, hypofibrinogenaemia, and ferritin greater than 500 μg/L as separate criteria
  • The article's own introduction lists hypertriglyceridaemia and/or hypofibrinogenaemia as a single criterion among the eight; counted that way, the listed findings meet four criteria
  • Nivolumab and ipilimumab were withheld and dexamethasone 10 mg twice daily was started, followed by rapid clinical improvement
  • The authors described the patient's improvement as following corticosteroid therapy given after infection had been reasonably excluded
  • In the patient, fever resolved, mental state normalised, liver tests improved and blood counts gradually recovered
  • The patient was discharged home on day 10 of admission on a tapering course of dexamethasone
• The authors' conclusion: The authors concluded that ICI-associated HLH is a rare but potentially life-threatening complication of cancer immunotherapy, and that early recognition, exclusion of alternatives such as infection, and prompt corticosteroids may result in rapid improvement
• Limitations the authors state:
  • The diagnosis was 'probable': haemophagocytosis was not demonstrated, and NK-cell activity and soluble CD25 test results were not available

Topics

Medical terms in this study, explained in our Lexicon: Ipilimumab (Yervoy), Nivolumab (Opdivo), Pleural Mesothelioma, checkpoint inhibitors.

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• Efficacy of nivolumab and ipilimumab in patients with malignant pleural mesothelioma is related to a subtype of effector memory cytotoxic T cells: Translational evidence from two clinical trials — J.M. Mankor, M.J. Disselhorst, et al. (2020)
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• Perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma: a phase 2 trial and ctDNA analyses — J.E. Reuss, P.K. Lee, et al. (2025)
• Real-World Outcomes of Patients With Malignant Pleural Mesothelioma Receiving a Combination of Ipilimumab and Nivolumab as First- or Later-Line Treatment — S. Schmid, L. Holer, et al. (2024)

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