Hemophagocytic lymphohistiocytosis with advanced malignant melanoma accompanied by ipilimumab and nivolumab: A case report and literature review

Abstract

Combination therapy with nivolumab + ipilimumab was recently approved for treating unresectable cases of malignant melanoma. In spite of the high response rate, it is associated with a high incidence of serious adverse events, including immune‐related hemophagocytic syndrome/hemophagocytic lymphohistiocytosis (irHPS/HLH), a difficult to diagnose rare disease. This is the first report of this disease in an Asian malignant melanoma patient treated with nivolumab + ipilimumab. A 69‐year‐old Japanese woman with unresectable malignant melanoma was treated with nivolumab + ipilimumab. Following the combined therapy, her fever and symptoms of malaise occurred, and she visited to our hospital's emergency department. Blood tests revealed significant liver dysfunction, anemia, and thrombocytopenia. We suspected irHPS/HLH, based on tests revealing decreased fibrinogen and significantly increased ferritin. Bone marrow biopsy revealed numerous macrophages and high hemophagocytosis levels. After 50 mg prednisolone (1 mg/kg per day) was administered, fever and cytopenia markedly improved. irHPS/HLH has a high rate of coagulation abnormalities accompanied by hypertriglyceridemia and hypofibrinogenemia, which are unlikely to occur in adult HPS/HLHs. Because irHPS/HLH responds better to steroids than other secondary HPS/HLHs, we expect a complete cure with steroids. Quick diagnosis and appropriate treatment based on clinical symptoms and laboratory tests are needed in suspected cases.

Gastric cancer complicated with hemophagocytic lymphohistiocytosis: case report and a brief review

“…One literature review includes 16 reports involving a total of 20 patients who were diagnosed with HLH secondary to a solid tumor (Table 2). Among the patients, 8 received immune checkpoint inhibitors (16)(17)(18)(20)(21)(22)(23)(24), 8 underwent chemotherapy (11)(12)(13)(14), and 4 were only diagnosed with a solid tumor (9,10,15,19). Thus, the application of immunotherapy as well as some HLH patients who are misdiagnosed as neoplastic fever may increase the incidence of HLH, which requires more attention.…”

Hemophagocytic Lymphohistiocytosis after Initiation of Combined Immunotherapy for Metastatic Melanoma

“…Even though the onset of HLH may occur at any time under ICI treatment, it appears that early onset of HLH is more likely. Most importantly, however, fatal outcome was reported in 16.2% of ICI-induced HLH cases -a rate that seems to be smaller than the death rates (up to 50%) reported for patients with HLH associated with other causes [1][2][3][4][5][6][7][8][9][10].…”

“…Primary or hereditary HLH (e.g., A91V mutation in PRF1) must be differentiated from secondary HLH, which is predominantly caused by infections, malignancies, and autoimmune conditions, frequently in the context of underlying immunodeficiency or immunosuppression. HLH is usually characterized by recurrent high fever, splenomegaly, pancytopenia, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, increased IL-2R, and hemophagocytosis on bone marrow assessment [1][2][3][4][5][6][7][8][9][10]. Here we report a patient with metastatic melanoma who developed HLH after initiation of anti-CTLA-4/PD-1 treatment and give a brief tabular overview on previously reported cases.…”

Ganglionar tuberculosis infection evolving to hemophagocytic lymphohistiocytosis after anti-programmed cell death 1 treatment for high-risk melanoma: a case report

“…Mtb infections have also been identified following exposure to anti-PD-1 monoclonal antibodies [ 15 ] used as monotherapy or in combination with anti-CTLA-4 agents [ 16 ]. A retrospective study evaluated the development of TB in 1144 patients with malignancies after ICI (pembrolizumab, nivolumab, or atezolizumab) treatment.…”