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Haemophagocytic lymphohistiocytosis as a complication of combination anti-PD-1 and anti-CTLA-4 checkpoint inhibitor immunotherapy for metastatic melanoma, and the outcome of rechallenge with single-agent anti-PD-1 immunotherapy
  1. Zachary Holmes,
  2. Ashling Courtney and
  3. Alison Hiong
  1. Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  1. Correspondence to Dr Zachary Holmes; holmesz{at}


A woman with metastatic melanoma was treated with immunotherapy induction with ipilimumab and nivolumab and radiotherapy to liver metastases. The patient deteriorated shortly thereafter, becoming febrile and hypotensive and requiring admission to the intensie care unit (ICU) for inotrope support. Failure to respond to antibiotics and a negative septic screen prompted further investigation, which ultimately led to a diagnosis of haemophagocytic lymphohistiocytosis (HLH). The patient improved on high dose steroids and was discharged home. Months later, in the context of progressive melanoma, the patient was re-challenged with nivolumab monotherapy and subsequently experienced recurrence of HLH, confirming the aetiology as being immunotherapy related. This case serves as a reminder to consider HLH where there are fevers of unknown origin in an unwell patient receiving immune checkpoint inhibitor therapy and also highlights immunotherapy as a potential cause for HLH, which has rarely been reported in the literature to date.

  • Cancer intervention
  • Haematology (incl blood transfusion)
  • Skin cancer
  • Unwanted effects / adverse reactions

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  • Contributors ZH provided care to the patient while she was in the hospital and was also the principal contributor to the drafting of the report. AH also provided care to the patient during her admission and also contributed to the writing and editing of the report. AC contributed significantly to researching and editing the article.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.