Some clinical trials have described improved outcomes in patients who develop immune-related adverse events (irAEs) while receiving immune checkpoint inhibitors for advanced melanoma. It is unknown if this effect would be seen in a real-world population. This is a single-center retrospective analysis of all patients receiving single-agent PD-1 inhibitor for unresectable stage III or stage IV melanoma between 2012 and 2018. The majority of patients had cutaneous melanoma and were elderly (put in median and range). Totally 33.3% were BRAF mutated and 66.7% had PD-1 inhibitor as first-line treatment for metastatic disease. Also, 22% of patients had brain metastases at presentation. Of the 87 patients included in this analysis, 48 (55%) developed at least one irAE. Dermatologic toxicities were the most common irAE. The median time to develop any irAE was 12 weeks. Only one patient died of immune-related toxicity. Overall survival in the population of patients that had an irAE was significantly greater than those that did not have any toxicity (21.1 vs. 7.5 months; P < 0.001). The development of endocrine toxicity had the strongest correlation with survival as did patient with grade 1 (NCI V.5) toxicity. The development of multiple toxicities did not correlate with survival. In patients with multiple toxicities, the type of irAE that presented initially did not impact the outcome. These findings add to the growing body of literature suggesting an association between irAEs and immune-checkpoint inhibitor efficacy while suggesting that this benefit may depend on the type of toxicity and severity.

中文翻译：

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PD -1 抑制剂治疗的转移性黑色素瘤中免疫相关不良事件发生的影响。


一些临床试验描述了在接受免疫检查点抑制剂治疗晚期黑色素瘤时发生免疫相关不良事件 (irAE) 的患者的预后得到改善。目前尚不清楚这种效应是否会在现实世界的人群中出现。这是对 2012 年至 2018 年间所有接受单药 PD-1 抑制剂治疗不可切除的 III 期或 IV 期黑色素瘤患者的单中心回顾性分析。大多数患者患有皮肤黑色素瘤，并且是老年人（按中位数和范围计算）。共有 33.3% 的患者存在 BRAF 突变，66.7% 的患者使用 PD-1 抑制剂作为转移性疾病的一线治疗。此外，22% 的患者就诊时患有脑转移。在本次分析中纳入的 87 名患者中，48 名患者 (55%) 出现至少一种 irAE。皮肤毒性是最常见的 irAE。发生任何 irAE 的中位时间为 12 周。只有一名患者死于免疫相关毒性。发生 irAE 的患者群体的总生存期显着高于没有任何毒性的患者群体（21.1 个月与 7.5 个月；P < 0.001）。内分泌毒性的发生与生存的相关性最强，1 级 (NCI V.5) 毒性的患者也是如此。多种毒性的发生与生存无关。在患有多种毒性的患者中，最初出现的 irAE 类型不会影响结果。这些发现丰富了越来越多的文献，表明 irAE 与免疫检查点抑制剂功效之间存在关联，同时表明这种益处可能取决于毒性类型和严重程度。