Treatment-refractory immune checkpoint inhibitor-induced hemophagocytic lymphohistiocytosis in the setting of adjuvant pembrolizumab for resected stage IIC melanoma: a case report
Abstract
Hemophagocytic lymphohistiocytosis is rare and does not have any distinct clinical features or laboratory abnormalities, whereby a high index of suspicion is required for diagnosis. Hemophagocytic lymphohistiocytosis can be divided into primary/genetic or secondary causes that can be immunotherapy-induced. With the increasing use of immune checkpoint inhibitors for treatment of multiple solid tumor malignancies, the incidence of rare complications such as hemophagocytic lymphohistiocytosis can be expected to rise. We describe a fatal case of immunosuppression-refractory pembrolizumab-induced hemophagocytic lymphohistiocytosis complicated by secondary disseminated fungal infection. A 75-year-old white Australian man with resected stage IIC melanoma who received four cycles of adjuvant pembrolizumab presented 11 weeks after commencement with febrile neutropenia, elevated C-reactive protein, and nonspecific symptoms. He developed progressive transaminitis, acute kidney injury, pancytopenia, hyperferritinemia, and hypofibrinogenemia. In addition, a bone marrow aspiration and trephine biopsy demonstrated hemophagocytosis. Treatment was commenced with high-dose corticosteroids and mycophenolate mofetil initially for suspected immune-related side effects, followed by tocilizumab and anakinra once a diagnosis of hemophagocytic lymphohistiocytosis was made. Unfortunately, his disease was refractory to treatment with development of multiorgan failure secondary to hemophagocytic…
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