Myasthenic crisis and polymyositis induced by one dose of nivolumab

Abstract

An 80‐year‐old man, who developed multiple lymph node and skin metastasis of malignant melanoma, received nivolumab monotherapy. Two weeks after the first dose, he experienced anorexia and fatigue, and suffered from progressive, severe dyspnea and muscle weakness. We diagnosed him with myocarditis, myositis, and myasthenic crisis induced by nivolumab. We commenced steroid therapy, immune absorption therapy, plasma exchange therapy, and i.v. immunoglobulin therapy, and succeeded in saving his life. Because his serum level of anti‐acetylcholine receptor antibodies in a sample collected before nivolumab treatment were positive and were elevated significantly after nivolumab, we suspected that nivolumab triggered a severe autoimmune response, which progressed subclinical myasthenia gravis to myasthenic crisis. We carried out T cell receptor repertoire analysis using next‐generation sequencing technologies and identified infiltration of clonally expanded T cell populations in the skeletal muscle after nivolumab treatment, implying a very strong T cell immune response against muscular cells. To avoid severe immune‐related adverse events, the exclusion of patients with subclinical autoimmune disease is very important for treatment with immune checkpoint inhibitors.

Immune checkpoint inhibitor‐induced lymphocytic fasciitis

“…While neither high peripheral eosinophilia nor eosinophils on biopsy is essential to a diagnosis of eosinophilic fasciitis, the absence of both in our case combined with the histopathological findings and temporal relationship to nivolumab, leave an anti‐programmed cell‐death‐protein‐1‐induced lymphocytic fasciitis as the diagnosis. Interestingly, the histology showed morphology atypical for eosinophilic fasciitis with florid lymphocytic infiltration, as seen in other IRAE in connective tissues (cardiac, skeletal muscle) following nivolumab …”

Guillain–Barré‐like syndrome during pembrolizumab treatment

“…Immune checkpoint inhibitors have shown promise in improving survival in several solid tumors, but irAEs are increasingly recognized and can occasionally be severe or fatal. Neurological irAEs for the class of immune checkpoint inhibitors include encephalitis, myelitis, meningitis, meningoradiculitis, GBS, peripheral neuropathy, myasthenic syndromes, and myositis . Since the recent approval of five PD‐1/PD‐L1 immune checkpoint inhibitors, numerous other irAEs have been described, including 2 cases of Guillain‐Barré‐like syndrome associated with pembrolizumab.…”

Nivolumab‐induced sialadenitis

“…In the past reports of ICIs‐induced irAEs such as colitis myocarditis, or pneumonitis, biopsies demonstrate dominant infiltration of CD8+ T cells at injured tissues . We performed immunostaining of tissues from our patient’s salivary gland using CD4 and CD8 antibodies, but CD8+ T cell did not show remarkable dominance in number or particular distribution around injured glands.…”