Abstract
BackgroundImmune checkpoint inhibitors (ICIs) have provided more options in the treatment of lung cancer. However, ICIs can cause several unfavorable reactions generally referred to as immune-related adverse effects.Case presentationIn this report, we present the case of a 52-year-old woman with successful regression of pleomorphic carcinoma of the lung following nivolumab therapy. She developed purpura fulminans (PF) ultimately resulting in amputation of both lower extremities. Blood tests revealed thrombocytopenia with increased serum soluble IL-2 receptor, ferritin, and triglyceride levels suggesting hemophagocytic lymphohistiocytosis (HLH). In addition, serum A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 activity was decreased, suggesting thrombotic thrombocytopenic purpura (TTP). Further detailed analysis revealed severe hypercytokinemia including increased levels of IL-1β, IL-6, IL-10, TNFα, IFNγ, and G-CSF.ConclusionThe severe systemic inflammatory reaction and impaired peripheral circulation in this patient was attributed to excessive immunological effect induced by nivolumab resulting in cytokine release syndrome (CRS). This is the first report of a patient with multiple pathological conditions including HLH, TTP-like condition, and PF presumably arising from ICI-induced CRS. Further accumulating thoroughly investigated cases would lead to better understanding of the disease and development of reliable cancer immunotherapy.
Highlights
Immune checkpoint inhibitors (ICIs) have provided more options in the treatment of lung cancer
ICI therapy has resulted in outstanding success on the one hand and lethal immune-related adverse effects on the other, which are becoming a major concern in further development of reliable cancer
We propose that all the deleterious hematopoietic adverse effects seen in this case can be attributed to cytokine release syndrome (CRS) induced by nivolumab-mediated overactivated immune reaction
Summary
We encountered a case of multiple pathologies including HLH, TTP-like condition, and PF presumably arising from ICI-induced CRS. Our current case showed significantly high blood concentration of IL-1β, IL-6, TNFα, and IFNγ when compared with previous reports of CRS [18,19,20], we did not use the inhibitory agents for inflammatory cytokines in this case because these were not yet recommended in the actual clinical setting at that time. A study reported that administration of anti-IL-6 receptor monoclonal antibody (tocilizumab) was useful for treatment of CRS [12]. Apart from tocilizumab, anti-TNFα and anti-IL-1 receptor monoclonal antibodies are commercially available. Combination of these anti-cytokine medications would be a promising approach for treating CRS. Abbreviations ADAMST13: A disintegrin and metalloprotease with thrombospondin type 1 motifs; CRS: Cytokine release syndrome; HLH: Hemophagocytic lymphohistiocytosis; ICI: Immune checkpoint inhibitor; PF: Purpura fulminans; TTP: Thrombotic thrombocytopenic purpura
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