Department of Medical Oncology, UMC Utrecht, Utrecht, The Netherlands.
University Medical Center Utrecht, Julius Centrum voor Gezondheidswetenschappen en Eerstelijns Geneeskunde, Utrecht, The Netherlands.
ESMO Open. 2020 Nov;5(6):e000945. doi: 10.1136/esmoopen-2020-000945.
Immune checkpoint inhibitor (ICI) can cause severe and sometimes fatal immune-related adverse events (irAEs). Since these irAEs mimick immunological disease, a female predominance has been speculated on. Nevertheless, no demographic or tumour-related factors associated with an increased risk of irAEs have been identified until now.
Risk ratios of severe (grade ≥3) irAEs for age, sex, WHO performance status, number of comorbidities, stage of disease, number of metastases and serum lactate dehydrogenases (LDH) were estimated using data from anti-PD1-treated patients with advanced melanoma in the prospective nationwide Dutch Melanoma Treatment Registry.
111 (11%) out of 819 anti-programmed cell death 1 treated patients experienced severe irAEs. Patients with non-lung visceral metastases (stage IV M1c or higher) less often experienced severe irAEs (11%) compared with patients with only lung and/or lymph node/soft tissue involvement (stage IV M1b or lower; 19%; adjusted risk ratio (RR) 0.63; 95% CI 0.41 to 0.94). Patients with LDH of more than two times upper limit of normal had a non-significantly lower risk of developing severe irAEs than those with normal LDH (RR 0.65; 95% CI 0.20 to 2.13). None of the other variables were associated with severe irAEs.
In patients with melanoma, more advanced disease is associated with a lower rate of severe irAEs. No association with sex was found.
免疫检查点抑制剂（ICI）可引起严重且有时致命的免疫相关不良反应（irAE）。由于这些 irAE 模仿免疫性疾病，因此推测女性发病更为多见。然而，到目前为止，尚未确定与 irAE 风险增加相关的任何人口统计学或肿瘤相关因素。
使用来自前瞻性全国性荷兰黑色素瘤治疗登记处的数据，对接受抗 PD1 治疗的晚期黑色素瘤患者，估计严重（≥3 级）irAE 的年龄、性别、世界卫生组织（WHO）体能状态、合并症数量、疾病分期、转移数量和血清乳酸脱氢酶（LDH）的风险比。
在 819 例接受抗程序性细胞死亡 1 治疗的患者中，有 111 例（11%）发生严重 irAE。与仅肺和/或淋巴结/软组织受累（IV 期 M1b 或更低；19%）的患者相比，有非肺部内脏转移（IV 期 M1c 或更高；11%）的患者较少发生严重 irAE（调整风险比（RR）0.63；95%置信区间 0.41 至 0.94）。与 LDH 正常上限的两倍以上的患者相比，LDH 正常的患者发生严重 irAE 的风险无显著降低（RR 0.65；95%置信区间 0.20 至 2.13）。其他变量均与严重 irAE 无关。
在黑色素瘤患者中，更晚期的疾病与严重 irAE 发生率较低相关。未发现与性别相关。
