Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Antoine, UPMC University Paris 06, 184, rue du Faubourg Saint-Antoine, 75012, Paris, France.
INSERM U938, Centre de Recherche Saint-Antoine (CRSA), Sorbonne Universités, UMPC University Paris 06, Paris, France.
Clin Rheumatol. 2019 Feb;38(2):601-602. doi: 10.1007/s10067-018-4373-y. Epub 2018 Nov 19.
Immune-related adverse events (irAEs), have been reported under immune checkpoint inhibitors. Nivolumab plus ipilimumab (N + I) demonstrated meaningful improvements in key patient-reported outcomes, in patients with pretreated microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). We report a case of severe necrotizing myositis which occurred in a patient treated with N + I combination for mCRC MSI-H. A 61-year-old woman was diagnosed with mCRC MSI-H and BRAFV600E mutated with synchronous liver, pleural, and lymph nodes metastases. After she failed to respond to standard chemotherapy (two lines with 5-fluorouracil, oxaliplatin, and irinotecan + bevacizumab), she received in a clinical trial (CheckMate 142), nivolumab 3 mg/kg, and ipilumumab 1 mg/kg every 3 weeks [4]. One week after the second infusion, she developed rapidly extending proximal muscles weakness associated with diffuse erythematous rash with grade 2/5 strength on abdominal, dorsal, and proximal limb muscles and impressive muscular edema. The creatine kinase level was at 14827 U/L (0-160 U/L), without any detectable autoantibodies. The electromyogram showed a severe myogenic syndrome, and muscular histological analysis demonstrated extensive muscular necrosis, with scarce lymphocytic infiltrates and pathological expression of class I HLA and C5b9 complement deposits with severe endomysial edema. N-I therapy was discontinued. Intravenous methylprednisolone was initiated for 3 days followed by 1 mg/kg/day orally, combined with intravenous immunoglobulins (2 g/kg/day for 2 days). At 3 years of first infusion of N + I, patient is without any new progressive disease, in partial response on the liver, pleural, and nodes metastasis, with only persistent minor psoas weakness.
免疫相关不良事件（irAEs）已在免疫检查点抑制剂下报告。纳武利尤单抗联合伊匹单抗（N + I）在预处理微卫星不稳定高（MSI-H）转移性结直肠癌（mCRC）患者的关键患者报告结局方面显示出有意义的改善。我们报告了一例严重坏死性肌炎病例，该病例发生在接受 N + I 联合治疗 MSI-H mCRC 的患者中。一名 61 岁女性被诊断为 mCRC MSI-H，BRAFV600E 突变，同时存在肝、胸膜和淋巴结转移。在她对标准化疗（氟尿嘧啶、奥沙利铂和伊立替康+贝伐珠单抗两线治疗）无反应后，她参加了一项临床试验（CheckMate 142），接受纳武利尤单抗 3mg/kg 和伊匹单抗 1mg/kg，每 3 周一次[4]。第二次输注后一周，她出现了迅速扩展的近端肌肉无力，伴有弥漫性红斑疹，腹部、背部和近端肢体肌肉肌力为 2/5 级，肌肉水肿明显。肌酸激酶水平为 14827U/L（0-160U/L），未检测到任何自身抗体。肌电图显示严重的肌原性综合征，肌肉组织学分析显示广泛的肌肉坏死，淋巴细胞浸润稀少，I 类 HLA 和 C5b9 补体沉积物的病理性表达伴有严重的肌内膜水肿。N-I 治疗被停止。静脉注射甲基强的松龙 3 天，随后口服 1mg/kg/天，同时静脉注射免疫球蛋白（2g/kg/天，连用 2 天）。在首次输注 N + I 3 年后，患者无任何新的进行性疾病，肝、胸膜和淋巴结转移部分缓解，仅持续存在轻微的腰肌无力。
