Osaki Megumu, Tachikawa Ryo, Ohira Junichiro, Hara Shigeo, Tomii Keisuke
Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Department of Neurology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.
Invest New Drugs. 2021 Feb;39(1):251-255. doi: 10.1007/s10637-020-00974-7. Epub 2020 Jul 10.
Immune checkpoint inhibitors can induce immune-related adverse events (irAEs) in different organs. Dermatomyositis is a rare form of systemic irAE. Although dermatomyositis-specific antibodies, especially anti-transcriptional intermediary factor 1-γ (anti-TIF1-γ) antibodies, have been detected in a few cases of immune checkpoint inhibitor-associated dermatomyositis, their titers before immunotherapy have not been examined. We hereby report the first irAE case of dermatomyositis accompanied by seroconversion of anti-TIF1-γ antibody following nivolumab treatment for advanced lung adenocarcinoma. A 64-year-old Japanese male with an advanced lung adenocarcinoma (cT4N2M1a stage IVA) received nivolumab as third-line therapy. Skin rashes appeared two days later, and were treated with a topical steroid as just drug eruptions. 7 weeks later, he was emergently admitted because of high serum creatine kinase level. Clinical examination showed deteriorated rashes along with slightly weakened proximal muscles. Muscle biopsy revealed myopathic changes consistent with dermatomyositis. Anti-TIF1-γ antibody was positive, which was found to be within normal range before nivolumab administration. He was diagnosed with dermatomyositis and treated with systemic corticosteroids, tacrolimus, and intravenous immunoglobulin. However, these drugs showed limited effectiveness against the progression of muscle weakness. He died of respiratory failure due to lung cancer and muscle weakness progression 6 months after the admission. In conclusion, our case demonstrates that the development of dermatomyositis was causally related to immune activation by nivolumab. Given the potential exacerbation of autoimmune paraneoplastic disorders in cancer patients receiving immunotherapy, clinicians should be aware of early manifestations of systemic irAEs that require prompt diagnosis and intervention.
免疫检查点抑制剂可在不同器官诱发免疫相关不良事件(irAE)。皮肌炎是一种罕见的全身性irAE。尽管在少数免疫检查点抑制剂相关皮肌炎病例中检测到了皮肌炎特异性抗体,尤其是抗转录中介因子1-γ(抗TIF1-γ)抗体,但免疫治疗前其滴度尚未得到检测。我们在此报告首例在接受纳武单抗治疗晚期肺腺癌后出现抗TIF1-γ抗体血清转化并伴有皮肌炎的irAE病例。一名64岁的日本男性,患有晚期肺腺癌(cT4N2M1a ⅣA期),接受纳武单抗作为三线治疗。两天后出现皮疹,仅作为药物疹用外用类固醇治疗。7周后,因血清肌酸激酶水平升高而紧急入院。临床检查显示皮疹恶化,近端肌肉轻度无力。肌肉活检显示与皮肌炎一致的肌病改变。抗TIF1-γ抗体呈阳性,在纳武单抗给药前发现其在正常范围内。他被诊断为皮肌炎,并接受了全身性皮质类固醇、他克莫司和静脉注射免疫球蛋白治疗。然而,这些药物对肌肉无力进展的疗效有限。入院6个月后,他死于肺癌和肌肉无力进展导致的呼吸衰竭。总之,我们的病例表明皮肌炎的发生与纳武单抗引起的免疫激活有因果关系。鉴于接受免疫治疗的癌症患者自身免疫性副肿瘤性疾病可能会加重,临床医生应意识到全身性irAE的早期表现,需要及时诊断和干预。