Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, AP-HP.Centre - Université Paris Cité, Paris, France.
Department of Immunology, Hôpital Européen Georges Pompidou, AP-HP.Centre - Université Paris Cité, Paris, France.
Oncoimmunology. 2023 May 11;12(1):2204754. doi: 10.1080/2162402X.2023.2204754. eCollection 2023.
Immune checkpoint inhibitors (ICIs) are now standard of care in many cancers. They can generate immune-related adverse events (irAEs), but no biomarkers are available to identify patients who are more likely to develop irAEs. We assess the association between pre-existing autoantibodies and occurrence of irAEs.
We prospectively collected data from consecutive patients receiving ICIs for advanced cancers, in a single center between May 2015 and July 2021. Autoantibodies testing was performed before ICIs initiation including AntiNeutrophil Cytoplasmic Antibodies, Antinuclear Antibodies, Rheumatoid Factor anti-Thyroid Peroxidase and anti-Thyroglobulin. We analyzed the associations of pre-existing autoantibodies with onset, severity, time to irAEs and with survival outcomes.
Of the 221 patients included, most had renal cell carcinoma (n = 99; 45%) or lung carcinoma (n = 90; 41%). Grade ≥2 irAEs were more frequent among patients with pre-existing autoantibodies: 64 (50%) vs. 20 (22%) patients (Odds-Ratio= 3.5 [95% CI=1.8-6.8]; p < 0.001) in the positive vs negative group, respectively. irAEs occurred earlier in the positive group with a median time interval between ICI initiation and irAE of 13 weeks (IQR = 8.8-21.6) vs. 28.5 weeks (IQR=10.6-55.1) in the negative group (p = 0.01). Twelve patients (9.4%) experienced multiple (≥2) irAEs in the positive group vs. 2 (2%) in the negative group (OR = 4.5 [95% CI: 0.98-36], p = 0.04). After a median follow-up of 25 months, median PFS and OS were significantly longer among patients experiencing irAE (p = 0.00034 and p = 0.016, respectively).
The presence of pre-existing autoantibodies is significantly associated with the occurrence of grade ≥2 irAEs, with earlier and multiple irAEs in patients treated with ICIs.
免疫检查点抑制剂（ICIs）现已成为许多癌症的标准治疗方法。它们会引发免疫相关不良事件（irAEs），但目前尚无生物标志物可用于识别更有可能发生 irAEs 的患者。我们评估了预先存在的自身抗体与 irAEs 发生之间的关系。
我们在 2015 年 5 月至 2021 年 7 月期间，在一家中心对接受 ICIs 治疗的晚期癌症连续患者前瞻性地收集数据。在开始使用 ICI 之前进行了自身抗体检测，包括抗中性粒细胞胞浆抗体、抗核抗体、类风湿因子、抗甲状腺过氧化物酶和抗甲状腺球蛋白。我们分析了预先存在的自身抗体与不良事件的发生、严重程度、发生时间以及与生存结果之间的关系。
在纳入的 221 名患者中，大多数患有肾细胞癌（n=99；45%）或肺癌（n=90；41%）。在有预先存在自身抗体的患者中，发生≥2 级 irAEs 的更为常见：阳性组 64 例（50%），阴性组 20 例（22%）（比值比[OR] = 3.5[95%CI=1.8-6.8]；p<0.001）。阳性组的 irAEs 更早发生，ICI 起始和 irAE 之间的中位时间间隔为 13 周（IQR=8.8-21.6），而阴性组为 28.5 周（IQR=10.6-55.1）（p=0.01）。阳性组中有 12 名（9.4%）患者发生了多种（≥2 种）irAEs，而阴性组中仅有 2 名（2%）患者发生（OR=4.5[95%CI：0.98-36]；p=0.04）。在中位随访 25 个月后，发生 irAE 的患者的中位 PFS 和 OS 明显更长（p=0.00034 和 p=0.016）。
预先存在的自身抗体的存在与发生≥2 级 irAEs 显著相关，并与 irAE 患者的更早和多种 irAE 相关。
