CHRU Brest, Brest, France.
Hôpital Ambroise Paré Boulogne-Billancourt, AP-HP, Boulogne-Billancourt, France.
Arthritis Rheumatol. 2019 Dec;71(12):2100-2111. doi: 10.1002/art.41068. Epub 2019 Oct 21.
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.
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.
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.
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.
癌症治疗用免疫检查点抑制剂（ICI）常引发免疫相关不良反应（IRAEs）。因此，大多数患有自身免疫性疾病的患者被排除在 ICI 的临床试验之外。本研究旨在评估患有自身免疫性疾病和癌症的患者使用 ICI 的安全性和疗效。
通过法国 3 个肿瘤学和自身免疫专家网络，于 2017 年 1 月至 2018 年 1 月进行了一项回顾性队列研究。评估了接受 ICI 治疗的患有自身免疫性疾病的成年人是否出现原有自身免疫性疾病的加重、其他 IRAEs 和癌症反应。
研究纳入了 112 例患者，中位随访时间为 8 个月。最常见的原有自身免疫性疾病为银屑病（n = 31）、类风湿关节炎（n = 20）和炎症性肠病（n = 14）。24 例患者（22%）在开始 ICI 治疗时接受免疫抑制治疗。79 例患者（71%）发生自身免疫性疾病加重和/或其他 IRAE，包括 53 例患者（47%）原有自身免疫性疾病加重和/或其他 IRAE，47 例患者（42%）发生其他 IRAE，48 例患者（43%）需要免疫抑制治疗，24 例患者（21%）永久停用 ICI。开始 ICI 治疗时接受免疫抑制治疗的患者中位无进展生存期更短（3.8 个月与 12 个月；P = 0.006），多变量分析也证实了这一点。发生原有自身免疫性疾病加重或其他 IRAE 的患者中位无进展生存期更短，但在未使用免疫抑制剂或未停用 ICI 的亚组中，生存情况更好。
我们的研究结果表明，在患有原有自身免疫性疾病的患者中，ICI 治疗常引发原有自身免疫性疾病加重或 IRAEs，但大多可控制而无需停用 ICI。基线时使用免疫抑制剂与较差的预后相关。
