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Abstract：
Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (p < 0.01), and had a better ECOG performance status (p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02-1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20-3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74-1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment.
摘要：
简介：辅助和晚期治疗的黑色素瘤患者之间抗PD-1治疗相关不良事件（irAEs）的发生率和严重程度差异尚不清楚。因为没有头对头研究比较这些组。方法：这项多中心队列研究分析了2015年至2021年间在辅助或晚期设置中接受抗PD-1治疗的黑色素瘤患者。治疗前评估合并症和ECOG表现状态，治疗期间监测III-IV级irAE。进行单变量和多变量回归分析以确定与irAE发展相关的因素。结果：共有1465例晚期黑色素瘤患者和908例切除的黑色素瘤患者接受了抗PD-1治疗。辅助治疗的患者更年轻，中位年龄为63岁，而晚期组为69岁(p<0.01)，具有较好的ECOG表现状态(p<0.01)。与接受辅助治疗的患者相比，晚期黑色素瘤患者的合并症更常见。76%对68%(p<0.01)。III-IV级irAE发生在214例（15％）晚期治疗患者和119例（13％）辅助治疗患者中。多变量分析显示，存在任何合并症（校正OR1.22，95％CI1.02-1.44）和ECOG状态大于1（校正OR2.00，95％CI1.20-3.32）时，严重irAE发展的风险增加。与晚期治疗相比，在纠正合并症和ECOG表现评分后，辅助治疗与irAE发展风险增加无关（校正OR0.95，95％CI0.74-1.21）。抗PD-1治疗因毒性（任何级别的irAE）而停止，在辅助治疗中比在晚期治疗中更常见。20%对15%(p<0.01)。结论：在辅助和晚期治疗的黑色素瘤患者中，较高的ECOG表现状态和任何合并症的存在与III-IV级irAE的风险增加独立相关。与晚期黑色素瘤患者相比，在辅助环境中治疗的患者发生严重irAE的风险没有增加。这些发现在咨询患者辅助抗PD-1治疗方面具有临床意义。
