Shigeaki Suzuki1, Nobuhisa Ishikawa2, Fumie Konoeda2, Nobuhiko Seki2, Satoshi Fukushima2, Kikuko Takahashi2, Hisashi Uhara2, Yoshikazu Hasegawa2, Shinichiro Inomata2, Yasushi Otani2, Kenji Yokota2, Takashi Hirose2, Ryo Tanaka2, Norihiro Suzuki2, Makoto Matsui2. 1. From the Department of Neurology (S.S., N. Suzuki), Keio University School of Medicine, Tokyo; Department of Respiratory Medicine (N.I.), Hiroshima Prefectural Hospital, Hiroshima; Department of Neurology (F.K.), Saiseikai Central Hospital, Tokyo; Division of Medical Oncology (N. Seki), Teikyo University School of Medicine, Tokyo; Department of Dermatology and Plastic Surgery (S.F.), Faculty of Life Sciences, Kumamoto University, Kumamoto; Department of Plastic and Reconstructive Surgery (K.T.), Hakodate Central General Hospital, Hokkaido; Department of Dermatology (H.U.), Sapporo Medical University School of Medicine, Hokkaido; Department of Medical Oncology (Y.H.), Izumi Municipal Hospital, Osaka; Department of Respiratory Medicine (S.I.), Sapporo Kosei Hospital, Hokkaido; Department of Oncology (Y.O.), Toyonaka Municipal Hospital, Osaka; Department of Dermatology (K.Y.), Nagoya University Graduate School of Medicine, Aichi; Department of Respiratory Medicine and Oncology (T.H.), Nippon Medical School Tama Nagayama Hospital, Tokyo; Department of Dermatology (R.T.), Kawasaki Medical School, Okayama; and Department of Neurology (M.M.), Kanazawa Medical College, Ishikawa, Japan. sgsuzuki@z3.keio.jp. 2. From the Department of Neurology (S.S., N. Suzuki), Keio University School of Medicine, Tokyo; Department of Respiratory Medicine (N.I.), Hiroshima Prefectural Hospital, Hiroshima; Department of Neurology (F.K.), Saiseikai Central Hospital, Tokyo; Division of Medical Oncology (N. Seki), Teikyo University School of Medicine, Tokyo; Department of Dermatology and Plastic Surgery (S.F.), Faculty of Life Sciences, Kumamoto University, Kumamoto; Department of Plastic and Reconstructive Surgery (K.T.), Hakodate Central General Hospital, Hokkaido; Department of Dermatology (H.U.), Sapporo Medical University School of Medicine, Hokkaido; Department of Medical Oncology (Y.H.), Izumi Municipal Hospital, Osaka; Department of Respiratory Medicine (S.I.), Sapporo Kosei Hospital, Hokkaido; Department of Oncology (Y.O.), Toyonaka Municipal Hospital, Osaka; Department of Dermatology (K.Y.), Nagoya University Graduate School of Medicine, Aichi; Department of Respiratory Medicine and Oncology (T.H.), Nippon Medical School Tama Nagayama Hospital, Tokyo; Department of Dermatology (R.T.), Kawasaki Medical School, Okayama; and Department of Neurology (M.M.), Kanazawa Medical College, Ishikawa, Japan.
Abstract
OBJECTIVE: To report the clinical features of myasthenia gravis (MG) induced by treatment with immune checkpoint inhibitors using 2-year safety databases based on postmarketing surveys in Japan. METHODS: We studied 10,277 patients with cancer who had received monotherapy with either nivolumab or ipilimumab between September 2014 and August 2016. As the control group, 105 patients with idiopathic MG were used. RESULTS: There were 12 MG cases (0.12%) among 9,869 patients with cancer who had been treated with nivolumab, but none among 408 patients treated with ipilimumab. These 12 patients included 6 men and 6 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 (nivoMG) included 4 patients with mild involvement and 8 patients with severe involvement. Bulbar symptoms and myasthenic crisis were observed more frequently in nivoMG than idiopathic MG. Ten patients were positive for anti-acetylcholine receptor antibodies. Serum creatine kinase levels were markedly elevated to an average level of 4,799 IU/L. Among the 12 patients with nivoMG, 4 had myositis and 3 had myocarditis, with 1 of these patients having both. Immunosuppressive therapy was effective. Postintervention status showed that pharmacologic remission or minimal manifestations were obtained in 4 patients; however, 2 patients died. Immune-related adverse events triggered by nivolumab impaired the patients' daily living activity. CONCLUSIONS: The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important.
OBJECTIVE: To report the clinical features of myasthenia gravis (MG) induced by treatment with immune checkpoint inhibitors using 2-year safety databases based on postmarketing surveys in Japan. METHODS: We studied 10,277 patients with cancer who had received monotherapy with either nivolumab or ipilimumab between September 2014 and August 2016. As the control group, 105 patients with idiopathic MG were used. RESULTS: There were 12 MG cases (0.12%) among 9,869 patients with cancer who had been treated with nivolumab, but none among 408 patients treated with ipilimumab. These 12 patients included 6 men and 6 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 (nivoMG) included 4 patients with mild involvement and 8 patients with severe involvement. Bulbar symptoms and myasthenic crisis were observed more frequently in nivoMG than idiopathic MG. Ten patients were positive for anti-acetylcholine receptor antibodies. Serum creatine kinase levels were markedly elevated to an average level of 4,799 IU/L. Among the 12 patients with nivoMG, 4 had myositis and 3 had myocarditis, with 1 of these patients having both. Immunosuppressive therapy was effective. Postintervention status showed that pharmacologic remission or minimal manifestations were obtained in 4 patients; however, 2 patients died. Immune-related adverse events triggered by nivolumab impaired the patients' daily living activity. CONCLUSIONS: The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important.