Wei Yanqiu, He Wei, Sun Wei, Wu Chaojie, Ren Denghua, Wang Xinmin, Zhang Mingshun, Huang Mao, Ji Ningfei
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Respiratory and Critical Care Medicine, Xishan People's Hospital of Wuxi City, Wuxi, China.
Transl Cancer Res. 2022 Aug;11(8):2960-2966. doi: 10.21037/tcr-22-154.
Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening state of immune hyperactivation. It has the highest mortality rate among all hematological immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs) when treating various cancers. However, the predisposing factors of HLH have rarely been mentioned in previous research.
Herein, we report 2 cases of HLH following treatment with pembrolizumab. A patient was diagnosed with thymic carcinoma (TC) and possible Sjögren's syndrome (SS), while another was diagnosed with non-small cell lung cancer (NSCLC) and Epstein-Barr virus (EBV) infection, and both were positive for antinuclear antibodies. Both cases experienced transient immune-related fever on day 7 after pembrolizumab administration and splenomegaly on day 10. Then recurrent high-grade fever appeared, and liver function impairment, highly elevated ferritin, and hypertriglyceridemia were tested. After the diagnosis of HLH, both patients were treated with dexamethasone and etoposide without relapse in our follow-up.
Considering the widespread use of ICIs and the high mortality rate of HLH, the immune-related fever, splenomegaly, and other signs of hyperinflammation after the infusion of ICIs, are worthy of attention to the presence of HLH. Preexisting autoimmune diseases (ADs) or positive antibodies, concomitant infection, and the setting of thymic epithelial tumors (TET) may be predisposing factors for HLH. And increased caution is needed before the initiation of ICIs for patients with 2 or more predisposing factors.
噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见的、危及生命的免疫过度激活状态。在免疫检查点抑制剂（ICI）治疗各种癌症时，它在所有血液学免疫相关不良事件（irAE）中死亡率最高。然而，HLH的诱发因素在以往研究中很少被提及。
在此，我们报告2例帕博利珠单抗治疗后发生HLH的病例。1例患者被诊断为胸腺癌（TC）且可能患有干燥综合征（SS），另1例被诊断为非小细胞肺癌（NSCLC）和爱泼斯坦-巴尔病毒（EBV）感染，两者抗核抗体均为阳性。两例患者在帕博利珠单抗给药后第7天均出现短暂的免疫相关发热，第10天出现脾肿大。随后出现反复高热，检测发现肝功能损害、铁蛋白高度升高和高甘油三酯血症。诊断为HLH后，两名患者均接受地塞米松和依托泊苷治疗，在我们的随访中均未复发。
考虑到ICI的广泛使用以及HLH的高死亡率，ICI输注后出现的免疫相关发热、脾肿大和其他炎症反应迹象，值得关注HLH的存在。既往存在的自身免疫性疾病（AD）或抗体阳性、合并感染以及胸腺上皮肿瘤（TET）的情况可能是HLH的诱发因素。对于有2种或更多诱发因素的患者，在开始ICI治疗前需要更加谨慎。
