Kuusisalo Saara, Koivunen Jussi P, Iivanainen Sanna
Department of Oncology and Radiotherapy, Oulu University Hospital and MRC Oulu, 90220 Oulu, Finland.
Cancers (Basel). 2022 May 3;14(9):2276. doi: 10.3390/cancers14092276.
Immune checkpoint inhibitors (ICIs) are associated with immune-related (ir) adverse events (AEs) resembling autoimmune diseases. In this retrospective cohort study of patients (pts) treated with ICIs at Oulu University Hospital from 2014-2020, we analysed the spectrum of severe irAEs and their prognostic nature, focusing on rare irAEs. Pts ( = 173) with lung cancer ( = 76, 43.9%), melanoma ( = 56, 32.4%), renal and bladder cancers ( = 34, 19.7%), head and neck cancers ( = 4, 2.3%), SCC ( = 2, 1.2%), and CRC ( = 1, 0.6%) receiving single anti-PD-(L)1 ( = 160) or combination (ICI-ICI = 9, ICI-chemotherapy = 4) therapy were included. The survival analysis focused on single anti-PD-(L)1-treated patients with melanoma, lung cancer, and renal and bladder cancers ( = 142). Grade ≥ 3 irAEs of multiple aetiology occurred in 29 patients treated with single-PD-L1 therapy (20.4%), which was associated with improved progression-free survival (PFS) (HR 0.50, CI 0.31-0.78) but not overall survival (OS) (HR 0.88, CI 0.52-1.50). Rare grade ≥ 3 events occurred in 10 (7.0%) pts with no association with PFS (HR 0.90, CI 0.42-1.94). Hence, the presence of rare grade ≥ 3 irAEs was associated with a tendency for inferior OS (HR 1.44, CI 0.66-3.11). Pts with rare grade ≥ 3 irAEs had inferior OS, possibly reflecting the delay in diagnostic workflow and the treatment of irAEs. One explanation for the high incidence of irAEs could be the Finnish population-based genetic variation affecting the immune system.
免疫检查点抑制剂（ICIs）与类似自身免疫性疾病的免疫相关（ir）不良事件（AEs）有关。在这项对2014年至2020年于奥卢大学医院接受ICIs治疗的患者（pts）进行的回顾性队列研究中，我们分析了严重irAEs的范围及其预后性质，重点关注罕见的irAEs。纳入了173例患有肺癌（76例，43.9%）、黑色素瘤（56例，32.4%）、肾癌和膀胱癌（34例，19.7%）、头颈癌（4例，2.3%）、皮肤鳞状细胞癌（SCC，2例，1.2%）和结直肠癌（CRC，1例，0.6%）的患者，他们接受了单药抗PD-（L）1治疗（160例）或联合治疗（ICI-ICI联合治疗9例，ICI-化疗联合治疗4例）。生存分析聚焦于接受单药抗PD-（L）1治疗的黑色素瘤、肺癌、肾癌和膀胱癌患者（142例）。接受单药PD-L1治疗的29例患者（20.4%）发生了多种病因的≥3级irAEs，这与无进展生存期（PFS）改善相关（风险比[HR]0.50，置信区间[CI]0.31 - 0.78），但与总生存期（OS）无关（HR 0.88，CI 0.52 - 1.50）。10例（7.0%）患者发生了罕见的≥3级事件，与PFS无关（HR 0.90，CI 0.42 - 1.94）。因此，罕见的≥3级irAEs的存在与OS较差的趋势相关（HR 1.44，CI 0.66 - 3.11）。发生罕见≥3级irAEs的患者OS较差，这可能反映了诊断流程和irAEs治疗的延迟。irAEs高发生率的一种解释可能是基于芬兰人群的影响免疫系统的基因变异。
