Department of Oncology.
Department of Medicine, Queen's University, Kingston, Ontario, Canada.
Melanoma Res. 2021 Jun 1;31(3):258-263. doi: 10.1097/CMR.0000000000000736.
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.
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的患者中出现免疫相关不良事件（irAEs）时，患者的结局得到改善。但目前尚不清楚这一效果是否会在真实世界的人群中出现。这是一项回顾性单中心分析，纳入了 2012 年至 2018 年间所有接受单药 PD-1 抑制剂治疗不可切除 III 期或 IV 期黑色素瘤的患者。大多数患者患有皮肤黑色素瘤且年龄较大（中位数和范围）。BRAF 突变的患者占大多数（33.3%），66.7%的患者将 PD-1 抑制剂作为转移性疾病的一线治疗药物。此外，22%的患者在就诊时已发生脑转移。在本分析中纳入的 87 例患者中，有 48 例（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。仅有 1 例患者死于免疫相关毒性。发生 irAE 的患者人群的总生存率明显高于未发生任何毒性的患者（21.1 个月 vs. 7.5 个月；P<0.001）。内分泌毒性的发生与生存具有最强的相关性，且 1 级毒性（NCI V.5）患者的生存获益最大。发生多种毒性与生存无相关性。在发生多种毒性的患者中，最初发生的 irAE 类型不会影响结局。这些发现增加了越来越多的文献证据，提示 irAEs 与免疫检查点抑制剂疗效之间存在关联，同时提示这种获益可能取决于毒性类型和严重程度。
