The objective of this study was to evaluate the utility of serum C-reactive protein (CRP) as biomarker for the early diagnosis of immune-related adverse events (irAEs) in melanoma patients treated with immune checkpoint inhibitors (ICIs) in the adjuvant setting, and its potential correlation with relapse-free survival (RFS). Prospectively collected data from 72 melanoma patients treated with adjuvant ICIs were pooled. CRP values at diagnosis of 10 irAEs were descriptively analysed. Correlations between RFS and the occurrence of irAEs, the grade of the irAE, the extent of CRP-elevation and the use of corticosteroids for irAE treatment were investigated. A total of 191 irAEs (grade 1/2, n = 182; grade 3/4, n = 9) occurred in 64 patients [skin toxicity (n = 70), fatigue (n = 50), thyroiditis (n = 12), musculoskeletal toxicity (n = 11), sicca syndrome (n = 10), other (n = 23), pneumonitis (n = 6), colitis (n = 4), hepatitis (n = 3) and hypophysitis (n = 2)]. In pneumonitis and hypophysitis, the median CRP levels at diagnosis exceeded the upper limit of normal (ULN, 5 mg/L). After a median follow-up of 26.5 months, 28 patients (39%) had been diagnosed with a melanoma relapse. Patients who experienced no irAE were at the highest risk for relapse (P = 0.008). A trend was observed for patients diagnosed with an irAE that was associated with an elevated CRP (>2xULN) to be at higher risk for relapse as compared to those diagnosed with an irAE and CRP <ULN (P = 0.054). CRP has potential as biomarker for the early detection of selected irAEs. Dynamic evaluation can guide irAE diagnosis, regression or relapse. The observed correlation between irAEs associated with an elevated CRP and risk for recurrence deserves further investigation.

中文翻译：

---

C反应蛋白作为辅助治疗中接受免疫检查点抑制剂治疗的黑色素瘤患者免疫相关不良事件的生物标志物。

本研究的目的是评估血清 C 反应蛋白 (CRP) 作为生物标志物在辅助治疗中接受免疫检查点抑制剂 (ICIs) 治疗的黑色素瘤患者免疫相关不良事件 (irAE) 早期诊断的效用，及其与无复发生存期（RFS）的潜在相关性。汇总了 72 名接受辅助 ICI 治疗的黑色素瘤患者的前瞻性数据。对 10 种 irAE 诊断时的 CRP 值进行了描述性分析。研究了 RFS 与 irAE 发生率、irAE 等级、CRP 升高程度以及 irAE 治疗中皮质类固醇的使用之间的相关性。64 名患者总共发生 191 例 irAE（1/2 级，n = 182；3/4 级，n = 9）[皮肤毒性（n = 70）、疲劳（n = 50）、甲状腺炎（n = 12） 、肌肉骨骼毒性 (n = 11)、干燥综合征 (n = 10)、其他 (n = 23)、肺炎 (n = 6)、结肠炎 (n = 4)、肝炎 (n = 3) 和垂体炎 (n = 2) )]。在肺炎和垂体炎中，诊断时的中位 CRP 水平超过正常上限（ULN，5 mg/L）。中位随访 26.5 个月后，28 名患者 (39%) 被诊断出黑色素瘤复发。未经历 irAE 的患者复发风险最高 (P = 0.008)。观察到的趋势是，与诊断为 irAE 且 CRP <ULN 的患者相比，诊断为与 CRP 升高 (>2xULN) 相关的 irAE 的患者复发风险更高 (P = 0.054)。CRP 有潜力作为早期检测选定 irAE 的生物标志物。动态评估可以指导irAE的诊断、消退或复发。观察到的与 CRP 升高相关的 irAE 与复发风险之间的相关性值得进一步研究。