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.
引言：目前尚无头对头研究比较辅助治疗与晚期治疗的黑色素瘤患者，因此抗PD-1治疗相关不良事件（irAEs）的发生率和严重程度差异尚不明确。方法：本项多中心队列研究分析了2015年至2021年间接受抗PD-1辅助治疗或晚期治疗的黑色素瘤患者。治疗前评估合并症及ECOG体能状态，治疗期间监测III-IV级irAEs。通过单因素及多因素回归分析确定与irAE发生相关的因素。结果：共1465例晚期黑色素瘤患者和908例已切除的黑色素瘤患者接受抗PD-1治疗。辅助治疗组患者更年轻（中位年龄63岁 vs 69岁，p<0.01），ECOG体能状态更佳（p<0.01）。晚期患者合并症发生率显著高于辅助治疗组（76% vs 68%，p<0.01）。III-IV级irAEs在晚期治疗组发生214例（15%），辅助治疗组发生119例（13%）。多因素分析显示，存在任何合并症（校正后OR 1.22，95% CI 1.02–1.44）及ECOG状态>1分（校正后OR 2.00，95% CI 1.20–3.32）与严重irAE发生风险增加相关。校正合并症和ECOG评分后，辅助治疗相较于晚期治疗并未增加irAE发生风险（校正后OR 0.95，95% CI 0.74–1.21）。因毒性反应（任何级别irAE）中止抗PD-1治疗的比例在辅助治疗组更高（20% vs 15%，p<0.01）。结论：较高的ECOG评分和存在合并症是辅助及晚期治疗黑色素瘤患者发生III-IV级irAE的独立风险因素。与晚期患者相比，辅助治疗患者并未增加发生严重irAEs的风险。这些发现对临床指导患者接受辅助性抗PD-1治疗具有重要意义。
Adverse Events in Anti-PD-1-Treated Adjuvant and First-Line Advanced Melanoma Patients
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