PDF(Pubmed)
Abstract：
Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune-related adverse events (irAE) are a frequent concern in clinical practice. The safety profile of ICI for the treatment of malignancies in patients diagnosed with autoimmune and cholestatic liver disease (AILD) remains unclear. Due to this uncertainty, these patients were excluded from ICI clinical trials and ICI are withheld from this patient group. In this retrospective multicenter study, we assessed the safety of ICI in patients with AILD.
We contacted tertiary referral hospitals for the identification of AILD patients under ICI treatment in Europe via the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Fourteen centers contributed data on AILD patients with malignancies being treated with ICI, another three centers did not treat these patients with ICI due to fear of irAEs.
In this study, 22 AILD patients under ICI treatment could be identified. Among these patients, 12 had primary biliary cholangitis (PBC), five had primary sclerosing cholangitis (PSC), four had autoimmune hepatitis (AIH), and one patient had an AIH-PSC variant syndrome. Eleven patients had hepatobiliary cancers and the other 11 patients presented with non-hepatic tumors. The applied ICIs were atezolizumab (n=7), durvalumab (n=5), pembrolizumab (n=4), nivolumab (n=4), spartalizumab (n=1), and in one case combined immunotherapy with nivolumab plus ipilimumab. Among eight patients who presented with grade 1 or 2 irAEs, three demonstrated liver irAEs. Cases with grades ≥ 3 irAEs were not reported. No significant changes in liver tests were observed during the first year after the start of ICI.
This European multicenter study demonstrates that PD-1/PD-L1 inhibitors appear to be safe in patients with AILD. Further studies on the safety of more potent dual immune checkpoint therapy are needed. We conclude that immunotherapy should not categorically be withheld from patients with AILD.
We contacted tertiary referral hospitals for the identification of AILD patients under ICI treatment in Europe via the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Fourteen centers contributed data on AILD patients with malignancies being treated with ICI, another three centers did not treat these patients with ICI due to fear of irAEs.
In this study, 22 AILD patients under ICI treatment could be identified. Among these patients, 12 had primary biliary cholangitis (PBC), five had primary sclerosing cholangitis (PSC), four had autoimmune hepatitis (AIH), and one patient had an AIH-PSC variant syndrome. Eleven patients had hepatobiliary cancers and the other 11 patients presented with non-hepatic tumors. The applied ICIs were atezolizumab (n=7), durvalumab (n=5), pembrolizumab (n=4), nivolumab (n=4), spartalizumab (n=1), and in one case combined immunotherapy with nivolumab plus ipilimumab. Among eight patients who presented with grade 1 or 2 irAEs, three demonstrated liver irAEs. Cases with grades ≥ 3 irAEs were not reported. No significant changes in liver tests were observed during the first year after the start of ICI.
This European multicenter study demonstrates that PD-1/PD-L1 inhibitors appear to be safe in patients with AILD. Further studies on the safety of more potent dual immune checkpoint therapy are needed. We conclude that immunotherapy should not categorically be withheld from patients with AILD.
摘要：
■近年来，免疫检查点抑制剂（ICI）彻底改变了许多恶性肿瘤的治疗方法。然而,免疫相关不良事件(irAE)是临床实践中经常关注的问题.ICI在诊断为自身免疫性和胆汁淤积性肝病（AILD）的患者中治疗恶性肿瘤的安全性仍不清楚。由于这种不确定性,这些患者被排除在ICI临床试验之外,而ICI被排除在该患者组中.在这项回顾性多中心研究中，我们评估了ICI在AILD患者中的安全性.
■我们通过欧洲肝病参考网络（ERNRARE-LIVER）联系了三级转诊医院，以确定在欧洲接受ICI治疗的AILD患者。14个中心提供了使用ICI治疗的AILD恶性肿瘤患者的数据，另外3个中心由于担心irAE而未使用ICI治疗这些患者。
■在这项研究中，可以确定22名接受ICI治疗的AILD患者。在这些患者中,12例原发性胆汁性胆管炎（PBC），5人患有原发性硬化性胆管炎（PSC），四个人患有自身免疫性肝炎（AIH），1例患者患有AIH-PSC变异综合征.11例患者患有肝胆癌，其他11例患者患有非肝肿瘤。应用的ICI是阿特珠单抗(n=7)，durvalumab（n=5），派姆单抗（n=4），Nivolumab（n=4），司他珠单抗（n=1），在一例中，纳武单抗联合伊匹单抗联合免疫治疗。在8名出现1级或2级irAE的患者中，三个显示肝脏iRAE。未报告≥3级irAE的病例。在ICI开始后的第一年中，未观察到肝脏检查的显着变化。
■这项欧洲多中心研究表明，PD-1/PD-L1抑制剂在AILD患者中似乎是安全的。需要进一步研究更有效的双重免疫检查点疗法的安全性。我们得出的结论是，AILD患者不应明确拒绝免疫治疗。
■我们通过欧洲肝病参考网络（ERNRARE-LIVER）联系了三级转诊医院，以确定在欧洲接受ICI治疗的AILD患者。14个中心提供了使用ICI治疗的AILD恶性肿瘤患者的数据，另外3个中心由于担心irAE而未使用ICI治疗这些患者。
■在这项研究中，可以确定22名接受ICI治疗的AILD患者。在这些患者中,12例原发性胆汁性胆管炎（PBC），5人患有原发性硬化性胆管炎（PSC），四个人患有自身免疫性肝炎（AIH），1例患者患有AIH-PSC变异综合征.11例患者患有肝胆癌，其他11例患者患有非肝肿瘤。应用的ICI是阿特珠单抗(n=7)，durvalumab（n=5），派姆单抗（n=4），Nivolumab（n=4），司他珠单抗（n=1），在一例中，纳武单抗联合伊匹单抗联合免疫治疗。在8名出现1级或2级irAE的患者中，三个显示肝脏iRAE。未报告≥3级irAE的病例。在ICI开始后的第一年中，未观察到肝脏检查的显着变化。
■这项欧洲多中心研究表明，PD-1/PD-L1抑制剂在AILD患者中似乎是安全的。需要进一步研究更有效的双重免疫检查点疗法的安全性。我们得出的结论是，AILD患者不应明确拒绝免疫治疗。
