Varied immuno-related adverse events induced by immune-check point inhibitors - Nivolumab-associated psoriasiform dermatitis related with increased serum level of interleukin-6.

Nivolumab is a standard recombinant antibody treatment for patients with malignant melanoma (MM), which functions as an immune checkpoint inhibitor by blocking the programmed cell death-1 (PD-1) pathway in T cells. However, it leads to various immune-related adverse events (irAEs), and also exacerbates underlying autoimmune diseases. Herein we report cases of MM with irAE. Case 1: A 69-year-old woman with MM developed destructive thyroiditis resulting in hypothyroidism after 3 doses of nivolumab, and had been treated with thyroid gland auxiliary therapy. Case 2: A 80-year-old man with MM developed an acute onset of hyperthyroidism after 4 doses of nivolumab. Case 3: A 85-year-old woman with MM developed polyradiculoneuropathy resulting in somatosensory disorder and muscle weakness after 2 doses of nivolumab, and had been treated with intravenous immunoglobulin and oral predonisolone (40 mg/day). Case 4: A 77-year-old man with MM developed psoriasiform dermatitis after local injections of IFN-β and 11 doses of nivolumab. Case 5: Case 2 also developed psoriasiform dermatitis. We analyzed serum levels of inflammatory cytokines in MM patients before/after treatments with nivolumab. All six patients who developed psoriasiform dermatitis with/without anamnesis of psoriasis after treatment with nivolumab, and all seven patients with other irAE exhibited increased serum IL-6 levels after nivolumab treatment, while decreased serum levels of IL-6 were observed in 5 of 7 non-afflicted MM patients. In addition, MM patients who achieved good responses to nivolumab significantly exhibited decreased serum TNF-α levels after nivolumab treatment compared to progressive MM patients.