Department of Gastroenterology, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), 94270, Le Kremlin-Bicêtre, France.
INSERM SC10-US19, Villejuif, France.
Eur J Cancer. 2019 Jan;106:106-114. doi: 10.1016/j.ejca.2018.10.006. Epub 2018 Nov 23.
Immune checkpoint inhibitors (ICIs), such as anti-CTLA-4 and anti-PD-1 antibodies, are effective against several malignancies. They are associated with gastrointestinal immune-related adverse events (GI-IrAEs), which may be severe and lead to ICI discontinuation. We assessed the risk of evolution of GI-IrAEs to chronic GI inflammation and the risk of recurrence after a second line of ICI.
This was a single-centre study. Included patients had a GI-IrAE due to ICIs between September 2010 and July 2017. We assessed the persistence of symptoms, endoscopic and/or histological inflammation, and the risk of recurrent GI-IrAEs after the second line of ICIs.
Eighty patients were included. The median follow-up was 8.4 months (0.36-72.3). The median duration of GI symptoms was 1.5 months (5 days-10.3 months): 1.4 months (7 days-4.9 months) with anti-CTLA-4, 2.0 months (5 days-10.3 months) with anti-PD-1 and 1.0 month (8 days-3.4 months) with combination therapy (log-rank test: p = 0.02). Three and 6 months after the beginning of GI-IrAEs, 22% (95% confidence interval: 14%-33%) and 5.4% (2.0%-14.7%) of patients had persistent symptoms, respectively. After a median of 6 months, 20/27 patients had endoscopic and/or histological inflammation, of whom, seven were symptom free. After the first episode, 6/26 patients relapsed after receiving another course of ICIs. Among these 26, 89% (77%-100%) had no recurrence after 3 months, 71% or 95% if the second line was anti-CTLA-4 or anti-PD-1, respectively.
GI-IrAEs seem to be acute or subacute, not chronic. Reintroduction of ICIs is possible in patients who had GI-IrAE.
免疫检查点抑制剂（ICIs），如抗 CTLA-4 和抗 PD-1 抗体，对多种恶性肿瘤有效。它们与胃肠道免疫相关不良事件（GI-IrAEs）相关，这些不良事件可能很严重，并导致 ICI 停药。我们评估了 GI-IrAEs 发展为慢性胃肠道炎症的风险，以及二线 ICI 后复发的风险。
这是一项单中心研究。纳入的患者在 2010 年 9 月至 2017 年 7 月期间因 ICI 发生 GI-IrAE。我们评估了症状持续存在、内镜和/或组织学炎症的情况，以及二线 ICI 后再次发生 GI-IrAE 的风险。
共纳入 80 例患者。中位随访时间为 8.4 个月（0.36-72.3）。胃肠道症状的中位持续时间为 1.5 个月（5 天-10.3 个月）：抗 CTLA-4 组为 1.4 个月（7 天-4.9 个月），抗 PD-1 组为 2.0 个月（5 天-10.3 个月），联合治疗组为 1.0 个月（8 天-3.4 个月）（对数秩检验：p=0.02）。GI-IrAE 开始后 3 个月和 6 个月时，分别有 22%（95%置信区间：14%-33%）和 5.4%（2.0%-14.7%）的患者存在持续性症状。中位时间为 6 个月时，27 例患者中有 20 例（74%）内镜和/或组织学有炎症，其中 7 例无症状。第一次发作后，26 例患者中有 6 例在接受另一疗程 ICI 后复发。在这 26 例患者中，89%（77%-100%）在 3 个月后无复发，如果二线治疗是抗 CTLA-4 或抗 PD-1，则分别为 71%或 95%。
GI-IrAEs 似乎是急性或亚急性的，不是慢性的。在发生过 GI-IrAE 的患者中，可以重新引入 ICI。
