ABSTRACT With increasing use of immune checkpoint inhibitors (ICIs) for advanced NSCLC, there is increasing recognition of immune‐related adverse events associated with ICI use. We recently reported increased incidence of checkpoint inhibitor pneumonitis (CIP) in ICI‐treated NSCLC patients. Since development of immune‐related adverse events in other organ systems has been associated with either no change or even improvement in tumor response/cancer outcomes, we sought to better understand the impact of CIP development on overall survival in ICI‐treated NSCLC patients. Using baseline and follow‐up data collected on a cohort of 205 ICI‐treated NSCLC patients, we used a multi‐state modeling approach to understand the effect of developing CIP on the risk of death. We observed time‐dependent changes in risk of developing and recovery from CIP, with an increased risk of both developing and recovering from CIP in the first year after initiating ICI. We found that developing CIP independently increased the risk of transitioning to death in both adjusted and unadjusted models. In the multivariate model, we found that the increase in mortality associated with CIP was only seen in patients with adenocarcinoma tumor histology. Collectively, these findings suggest that in NSCLC, development of CIP worsens survival in patients receiving immunotherapy.

中文翻译：

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检查点抑制剂肺炎对接受免疫检查点免疫治疗的非小细胞肺癌患者生存率的影响

摘要 随着免疫检查点抑制剂 (ICI) 越来越多地用于晚期 NSCLC，人们越来越认识到与 ICI 使用相关的免疫相关不良事件。我们最近报道了 ICI 治疗的 NSCLC 患者中检查点抑制剂肺炎 (CIP) 的发生率增加。由于其他器官系统中免疫相关不良事件的发展与肿瘤反应/癌症结果的无变化甚至改善有关，我们试图更好地了解 CIP 发展对 ICI 治疗的 NSCLC 患者总生存期的影响。使用在 205 名接受 ICI 治疗的 NSCLC 患者队列中收集的基线和随访数据，我们使用多状态建模方法来了解发生 CIP 对死亡风险的影响。我们观察到 CIP 发展和恢复风险的时间依赖性变化，在启动 ICI 后的第一年，发生 CIP 和从 CIP 中恢复的风险增加。我们发现独立开发 CIP 增加了调整和未调整模型中过渡到死亡的风险。在多变量模型中，我们发现与 CIP 相关的死亡率增加仅见于腺癌肿瘤组织学患者。总的来说，这些发现表明，在 NSCLC 中，CIP 的发展使接受免疫治疗的患者的生存率恶化。我们发现与 CIP 相关的死亡率增加仅见于腺癌肿瘤组织学患者。总的来说，这些发现表明，在 NSCLC 中，CIP 的发展使接受免疫治疗的患者的生存率恶化。我们发现与 CIP 相关的死亡率增加仅见于腺癌肿瘤组织学患者。总的来说，这些发现表明，在 NSCLC 中，CIP 的发展使接受免疫治疗的患者的生存率恶化。