晚期疾病患者发生严重免疫检查点抑制剂毒性的风险较低。
Lower risk of severe checkpoint inhibitor toxicity in more advanced disease.
机构信息
Department of Medical Oncology, UMC Utrecht, Utrecht, The Netherlands.
University Medical Center Utrecht, Julius Centrum voor Gezondheidswetenschappen en Eerstelijns Geneeskunde, Utrecht, The Netherlands.
出版信息
ESMO Open. 2020 Nov;5(6):e000945. doi: 10.1136/esmoopen-2020-000945.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
In patients with melanoma, more advanced disease is associated with a lower rate of severe irAEs. No association with sex was found.
背景
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。
方法
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。
结果
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。
结论
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。
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