Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Oncologist. 2019 Jun;24(6):e327-e337. doi: 10.1634/theoncologist.2018-0618. Epub 2019 Feb 22.
Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors.
Consecutive patients with advanced cancer, treated with anti-programmed death-1 (PD-1) agents, were evaluated according to the presence of pre-existing AIDs. The incidence of immune-related adverse events (irAEs) and clinical outcomes were compared among subgroups.
A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non-small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty-five patients (11.3%) had pre-existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre-existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive ( = .0005) and active pre-existing AIDs ( = .0162), female sex ( = .0004), and Eastern Cooperative Oncology Group Performance Status <2 ( = .0030) were significantly related to a higher incidence of irAEs of any grade. No significant differences were observed regarding grade 3/4 irAEs and objective response rate among subgroups. Pre-existing AIDs were not significantly related with progression-free survival and overall survival.
This study quantifies the increased risk of developing irAEs in patients with pre-existing AIDs who had to be treated with anti-PD-1 immunotherapy. Nevertheless, the incidence of grade 3/4 irAEs is not significantly higher when compared with control population. The finding of a greater incidence of irAEs among female patients ranks among the "hot topics" in gender-related differences in immuno-oncology.
Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors but are frequent in clinical practice. This study quantifies the increased risk of developing immune-related adverse events (irAEs) in patients with pre-existing AIDs who had to be treated with anti-programmed death-1 immunotherapy. Nevertheless, their toxicities are mild and the incidence of grade 3/4 irAEs is not significantly higher compared with those of controls. These results will help clinicians in everyday practice, improving their ability to offer a proper counselling to patients, in order to offer an immunotherapy treatment even to patients with pre-existing autoimmune disease.
患有自身免疫性疾病（AIDs）的患者通常未被纳入免疫检查点抑制剂的临床试验中。
连续收治了接受抗程序性死亡-1（PD-1）药物治疗的晚期癌症患者，并根据是否存在预先存在的 AIDs 进行评估。比较了亚组之间免疫相关不良事件（irAEs）和临床结局的发生率。
共纳入 751 例患者；中位年龄为 69 岁。原发肿瘤如下：非小细胞肺癌 492 例（65.5%）；黑色素瘤 159 例（21.2%）；肾癌 94 例（12.5%）；其他 6 例（0.8%）。男/女比例为 499/252。85 例（11.3%）患者有预先存在的 AIDs，进一步分为临床活动（17.6%）和非活动（82.4%）。与无 AIDs 的患者相比，有预先存在的 AIDs 的患者任何级别的 irAEs 发生率明显更高（65.9% vs. 39.9%）。多变量分析显示，无论是否存在预先存在的 AIDs（ = .0005）、女性（ = .0004）、Eastern Cooperative Oncology Group 体能状态 <2（ = .0030），均与任何级别的 irAEs 发生率较高显著相关。亚组间 3/4 级 irAEs 和客观缓解率无显著差异。预先存在的 AIDs 与无进展生存期和总生存期无关。
本研究量化了预先存在的 AIDs 患者接受抗 PD-1 免疫治疗时发生 irAEs 的风险增加。然而，与对照人群相比，3/4 级 irAEs 的发生率并不显著更高。女性患者 irAEs 发生率较高是免疫肿瘤学中性别差异的“热门话题”之一。
患有自身免疫性疾病（AIDs）的患者通常未被纳入免疫检查点抑制剂的临床试验中，但在临床实践中却很常见。本研究量化了预先存在的 AIDs 患者接受抗程序性死亡-1 免疫治疗时发生免疫相关不良事件（irAEs）的风险增加。然而，这些不良反应的毒性较轻，3/4 级 irAEs 的发生率与对照组相比并不显著更高。这些结果将有助于临床医生在日常实践中，提高为患者提供适当咨询的能力，以便为即使是有预先存在的自身免疫性疾病的患者提供免疫治疗。
