S12-4. Myasthenia gravis induced by immune checkpoint inhibitors

Abstract

The use of immune checkpoint inhibitors, which target regulatory pathways in T-cells to enhance antitumor responses, is leading to important clinical advances and providing new weapons against cancer. Antibodies against programmed death-1 (nivolumab and pembrolizumab) and an antibody against cytotoxic T-lymphocyte-associated antigen 4 (ipilimumab) are revolutionizing the treatment of an increasing number of tumor types. Using 2-year safety databases based on post-market surveys in Japan, we identified 12 myasthenia gravis (MG) cases (0.12%) among 9869 cancer patients who had been treated with nivolumab. These 12 patients included six men and six women with a mean age of 73.5 ± 6.3 years. MG onset occurred in the early phase after nivolumab treatment and rapidly deteriorated. Nivolumab-related MG included four patients with mild involvement and eight patients with severe involvement. Serum creatine kinase levels were markedly elevated to an average level of 4799 IU/L. Among the 12 nivoMG patients, four had myositis and three had myocarditis, with one of these patients having both. Immunosuppressive therapy was effective, however, two patients died. Immune-related adverse events triggered by nivolumab impaired the patients’ daily living activity. The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in cancer patients is important.