Diaz Laurine, Jauzelon Benjamin, Dillies Anne-Charlotte, Le Souder Cosette, Faillie Jean-Luc, Maria Alexandre Thibault Jacques, Palassin Pascale
Department of Medical Pharmacology and Toxicology, CHU Montpellier, Montpellier University, 34000 Montpellier, France.
Internal Medicine & Immuno-Oncology (MedI2O), CHU Montpellier, 34000 Montpellier, France.
J Clin Med. 2023 Mar 2;12(5):1985. doi: 10.3390/jcm12051985.
Acquired hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal condition characterized by hyperactivation of macrophages and cytotoxic lymphocytes, combining a series of non-specific clinical symptoms and laboratory disorders. Etiologies are multiple: infectious (mainly viral) but also oncologic, autoimmune or drug-induced. Immune checkpoint inhibitors (ICI) are recent anti-tumor agents associated with a novel profile of adverse events triggered by immune system over-activation. Here, we sought to provide a comprehensive description and analysis of HLH cases reported with ICI since 2014.
Disproportionality analyses were performed in order to further explore the association between ICI therapy and HLH. We selected 190 cases, 177 from the World Health Organization pharmacovigilance database and 13 from the literature. Detailed clinical characteristics were retrieved from the literature and from the French pharmacovigilance database.
The cases of HLH reported with ICI concerned men in 65% of cases with a median age of 64 years. HLH occurred in an average of 102 days after the initiation of ICI treatment and mostly concerned nivolumab, pembrolizumab and nivolumab/ipilimumab combination. All cases were considered serious. Most cases presented a favorable outcome (58.4%); however, death was reported for 15.3% of patients. Disproportionality analyses showed that HLH was seven times more frequently reported with ICI therapy than with other drugs and three times more than with other antineoplastic agents.
Clinicians should be aware of the potential risk of ICI-related HLH to improve the early diagnosis of this rare immune-related adverse event.
获得性噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见但可能致命的疾病，其特征为巨噬细胞和细胞毒性淋巴细胞过度活化，伴有一系列非特异性临床症状和实验室检查异常。病因多种多样：包括感染性（主要为病毒感染），也有肿瘤性、自身免疫性或药物诱导性。免疫检查点抑制剂（ICI）是近期的抗肿瘤药物，与免疫系统过度激活引发的新型不良事件相关。在此，我们试图对2014年以来报道的与ICI相关的HLH病例进行全面描述和分析。
进行不成比例分析以进一步探讨ICI治疗与HLH之间的关联。我们选取了190例病例，其中177例来自世界卫生组织药物警戒数据库，13例来自文献。从文献和法国药物警戒数据库中检索详细的临床特征。
报道的与ICI相关的HLH病例中，65%为男性，中位年龄为64岁。HLH平均在ICI治疗开始后102天发生，主要涉及纳武单抗、帕博利珠单抗以及纳武单抗/伊匹木单抗联合用药。所有病例均被视为严重病例。大多数病例预后良好（58.4%）；然而，15.3% 的患者报告死亡。不成比例分析表明，与ICI治疗相关的HLH报告频率比其他药物高7倍，比其他抗肿瘤药物高3倍。
临床医生应意识到ICI相关HLH的潜在风险，以改善对这种罕见的免疫相关不良事件的早期诊断。
