Safety and Efficacy of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Disease: A Nationwide, Multicenter Cohort Study
Safety and Efficacy of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Disease: A Nationwide, Multicenter Cohort Study
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DOI：
10.1002/art.41068
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发表时间：
2019-10-21
影响因子：
13.3
通讯作者：
Kostine, Marie
中科院分区：
文献类型：
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作者：
Tison, Alice;Quere, Gilles;Kostine, Marie
目的用于癌症治疗的免疫检查点抑制剂（ICIs）经常引起免疫相关不良反应（IRAEs）。因此，大多数既往存在自身免疫性疾病的患者被排除在ICIs的临床试验之外。本研究旨在评估ICIs在既往存在自身免疫性疾病和癌症患者中的安全性和有效性。方法2017年1月至2018年1月，通过3个法国肿瘤和自身免疫专家网络进行回顾性队列研究。已存在自身免疫性疾病的成年人在接受ICIs治疗时，评估已存在自身免疫性疾病的爆发、其他irae和癌症反应的发生情况。结果纳入112例患者，随访时间中位数为8个月。最常见的自身免疫性疾病是牛皮癣（n = 31）、类风湿关节炎（n = 20）和炎症性肠病（n = 14）。24例患者（22%）在ICI开始时接受免疫抑制治疗。79例（71%）患者发生自身免疫性疾病发作和/或其他IRAE，包括53例（47%）患者既往存在自身免疫性疾病发作和47例（42%）患者发生其他IRAE， 48例（43%）患者需要免疫抑制治疗，24例（21%）患者需要永久停止ICI治疗。多变量分析证实，ICI开始时接受免疫抑制治疗的患者的中位无进展生存期较短（3.8个月vs 12个月；P = 0.006）。先前存在自身免疫性疾病或其他IRAE发作的患者的中位无进展生存期较短，在不使用免疫抑制剂或停止ICI的亚组中有更好的生存趋势。结论：我们的研究结果表明，在既往存在自身免疫性疾病的患者中，经常发生耀斑或irae，但大多数情况下无需停用ICI即可控制。基线免疫抑制治疗与较差的预后相关。
Objective Immune checkpoint inhibitors (ICIs) for cancer therapy frequently induce immune-related adverse effects (IRAEs). Therefore, most patients with preexisting autoimmune diseases have been excluded from clinical trials of ICIs. This study was undertaken to evaluate the safety and efficacy of ICIs in patients with preexisting autoimmune disease and cancer. Methods A retrospective cohort study was conducted from January 2017 to January 2018 via 3 French national networks of experts in oncology and autoimmunity. Adults with preexisting autoimmune disease who were receiving ICIs were assessed for the occurrence of flare of preexisting autoimmune disease, other IRAEs, and cancer response. Results The study included 112 patients who were followed up for a median of 8 months. The most frequent preexisting autoimmune diseases were psoriasis (n = 31), rheumatoid arthritis (n = 20), and inflammatory bowel disease (n = 14). Twenty-four patients (22%) were receiving immunosuppressive therapy at ICI initiation. Autoimmune disease flare and/or other IRAE(s) occurred in 79 patients (71%), including flare of preexisting autoimmune disease in 53 patients (47%) and/or other IRAE(s) in 47 patients (42%), with a need for immunosuppressive therapy in 48 patients (43%) and permanent discontinuation of ICI in 24 patients (21%). The median progression-free survival was shorter in patients receiving immunosuppressive therapy at ICI initiation (3.8 months versus 12 months; P = 0.006), confirmed by multivariable analysis. The median progression-free survival was shorter in patients who experienced a flare of preexisting autoimmune disease or other IRAE, with a trend toward better survival in the subgroup without immunosuppressant use or ICI discontinuation. Conclusion Our findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes.