• Michael Krasovitsky and Jessica Borbasi.
• Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, NSW, Australia.
• Palliat Med. 2021 May 1; 35 (5): 972-976.

BackgroundImmunotherapy is increasingly used in the management of early and advanced malignancy. There is limited data regarding the associations between immunotherapy, malignancy, pain and haemophagocytic lymphohistiocytosis.CaseA 40-year-old woman was diagnosed with advanced melanoma, with metastases to her brain, liver, lung, adrenal glands and bone. She had moderate opioid requirements prior to the initiation of therapy. Following doublet immunotherapy with nivolumab and ipilimumab, she experienced a severe pain crisis associated with pyrexia and haemophagocytic lymphohistiocytosis.Possible Courses Of ActionManagement dilemmas included whether or not to initiate non-steroidal and steroidal anti-inflammatory therapies, how to address the patient's nociceptive, neuropathic and inflammatory pain, and how to manage the haemophagocytic lymphohistiocytosis.Formulation Of Management PlanThe patient required rapid up-titration of analgesia, including methadone, ketamine, hydromorphone, pregabalin and benzodiazepines. Ketorolac and high dose steroid therapy were administered for pain management and to mitigate treatment associated inflammation and haemophagocytic lymphohistiocytosis.OutcomeThe patient's pain was inadequately managed despite multimodal analgesia, and stigmata of inflammation progressed. She died 14 days following treatment.LessonsThe case demonstrates that severe pain may be a consequence of immunotherapy given for advanced, high volume melanoma.Research AvenuesThere is laboratory evidence suggesting an association between immunotherapy, malignancy, pain and haemophagocytic lymphohistiocytosis. Further clinical evidence is required in order to understand these intersecting phenomena.

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