内容紹介
Summary
The specific characteristics of neuromuscular immune-related adverse events(irAEs)including myasthenia gravis have not been elucidated because the frequency is generally low, ranging from 1-2% of cancer patients undergoing therapy with programmed cell death 1(PD-1)inhibitors. Inflammatory myopathy(myositis)is also one of the representative neuromuscular irAEs. A variety of studies have demonstrated that myositis as an irAE is often accompanied by ocular muscle symptoms, which physicians have often termed“myasthenia-like”or“pseudo-myasthenic”. We presented the clinical features of 19 Japanese patients with inflammatory myopathy associated with PD-1 inhibitors(PD-1 myopathy)(13 men and 6 women, mean age 70 years). Ten patients showed a mild form of disease and 9 patients showed a severe form. Non-small cell lung cancer was the most common underlying cancer. PD-1 inhibitor consisted of 11 nivolumab and 8 pembrolizumab. PD-1 myopathy occurred 29 days on average after the first administration of PD-1 inhibitor. Serum creatine kinase(CK)was increased to 5,247 IU/L on average. Autoantibodies related to inflammatory myopathy were negative, while anti-striational antibodies were found in 13(68%). Muscle pathology was characterized by multifocal necrotic myofibers with endomysial inflammation. Immunotherapy with corticosteroids was generally effective for muscle weakness with prompt normalization of serum CK levels. Myasthenia gravis and myositis induced by PD-1 inhibitors may have the common clinical features and pathological mechanisms.
要旨
免疫チェックポイント阻害剤の治療中に発症する神経・筋障害の有害事象の頻度は低いものの,重症筋無力症(myasthenia gravis: MG)や筋炎であるなど多彩な疾患が含まれる。programmed cell death 1(PD-1)抗体であるニボルマブあるいはペムブロリズマブの単剤投与により発症した筋炎の19例(M :F=13 :6,平均年齢70歳)の臨床像,自己抗体,筋病理を明らかにした。 9例は重症の筋症状を呈しており,原因となるがんのなかでは非小細胞肺がんが最多であった。ニボルマブ11例,ペムブロリズマブは8例で使用され,初回投与から29日で発症した。血清クレアチンキナーゼ(creatine kinase: CK)は平均5,247 IU/Lと著明に上昇していた。抗横紋筋抗体は13例(68%)で検出された。筋病理では筋線維が集簇的に壊死・再生を呈しているのが特徴的であった。免疫治療が有効であり,血清CKは早期に正常範囲まで低下した。病態機序や臨床像から免疫関連有害事象として発症するMGと筋炎は共通の病態を有する単独の疾患(PD-1ミオパチー)としてとらえるほうが適切であり,両疾患の可能性を念頭に置いた副作用対策方法が必要である。
目次
The specific characteristics of neuromuscular immune-related adverse events(irAEs)including myasthenia gravis have not been elucidated because the frequency is generally low, ranging from 1-2% of cancer patients undergoing therapy with programmed cell death 1(PD-1)inhibitors. Inflammatory myopathy(myositis)is also one of the representative neuromuscular irAEs. A variety of studies have demonstrated that myositis as an irAE is often accompanied by ocular muscle symptoms, which physicians have often termed“myasthenia-like”or“pseudo-myasthenic”. We presented the clinical features of 19 Japanese patients with inflammatory myopathy associated with PD-1 inhibitors(PD-1 myopathy)(13 men and 6 women, mean age 70 years). Ten patients showed a mild form of disease and 9 patients showed a severe form. Non-small cell lung cancer was the most common underlying cancer. PD-1 inhibitor consisted of 11 nivolumab and 8 pembrolizumab. PD-1 myopathy occurred 29 days on average after the first administration of PD-1 inhibitor. Serum creatine kinase(CK)was increased to 5,247 IU/L on average. Autoantibodies related to inflammatory myopathy were negative, while anti-striational antibodies were found in 13(68%). Muscle pathology was characterized by multifocal necrotic myofibers with endomysial inflammation. Immunotherapy with corticosteroids was generally effective for muscle weakness with prompt normalization of serum CK levels. Myasthenia gravis and myositis induced by PD-1 inhibitors may have the common clinical features and pathological mechanisms.
要旨
免疫チェックポイント阻害剤の治療中に発症する神経・筋障害の有害事象の頻度は低いものの,重症筋無力症(myasthenia gravis: MG)や筋炎であるなど多彩な疾患が含まれる。programmed cell death 1(PD-1)抗体であるニボルマブあるいはペムブロリズマブの単剤投与により発症した筋炎の19例(M :F=13 :6,平均年齢70歳)の臨床像,自己抗体,筋病理を明らかにした。 9例は重症の筋症状を呈しており,原因となるがんのなかでは非小細胞肺がんが最多であった。ニボルマブ11例,ペムブロリズマブは8例で使用され,初回投与から29日で発症した。血清クレアチンキナーゼ(creatine kinase: CK)は平均5,247 IU/Lと著明に上昇していた。抗横紋筋抗体は13例(68%)で検出された。筋病理では筋線維が集簇的に壊死・再生を呈しているのが特徴的であった。免疫治療が有効であり,血清CKは早期に正常範囲まで低下した。病態機序や臨床像から免疫関連有害事象として発症するMGと筋炎は共通の病態を有する単独の疾患(PD-1ミオパチー)としてとらえるほうが適切であり,両疾患の可能性を念頭に置いた副作用対策方法が必要である。