Department of Internal Medicine, Temple University Hospital, Philadelphia, Pennsylvania, USA.
Departments of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Oncologist. 2017 Oct;22(10):1232-1237. doi: 10.1634/theoncologist.2017-0133. Epub 2017 Jun 26.
The programmed death 1 (PD-1) checkpoint inhibitors (CKIs) can lead to immune-related adverse events (irAEs). We sought to evaluate whether the development of irAEs correlates with treatment response in non-melanoma malignancies.
We conducted a retrospective study of patients who received anti-PD-1 CKI monotherapy at Fox Chase Cancer Center. Endpoints included overall response rate (ORR), time to next therapy or death (TTNTD), and overall survival (OS). Fisher's exact tests and logistic regression models were used to determine the association between irAE incidence and ORR, and Kaplan-Meier curves with log-rank tests and Cox regression models were used for the comparison of TTNTD and OS.
Between November 2011 and November 2016, 160 patients were treated with >1 dose of an anti-PD-1 CKI. Seventy-three (46%) were treated on a clinical trial. Immune-related adverse events were noted in 64 patients (40%), with steroids required in 36 (23%). Of the 142 patients evaluable for clinical response, 28 patients (20%) achieved a partial response at first scan. An association between irAEs and ORR was seen in clinical trial patients ( = .007), but not in non-trial patients ( = .13). When controlling for clinical trial participation and cancer type using multivariate analysis, low-grade irAEs had higher ORR ( = .017) and longer TTNTD ( = .008). No association between irAE incidence and OS was seen ( = .827). Immune-related adverse events that required steroid treatment were marginally associated with increased TTNTD ( = .05, hazard ratio 0.62) but were not associated with OS ( = .13).
We demonstrate several positive associations between the development of irAEs and clinical outcomes in non-melanoma patients treated with PD-1 CKIs, for which further validation is required.
This study evaluated whether the development of immune-related adverse events in non-melanoma patients treated with programmed cell death 1 checkpoint inhibitors correlates with improved clinical outcomes. The results indicate that for a subset of patients, in particular those with low-grade immune-related adverse events, immune-related adverse events predicted for an improved response rate and longer time to next therapy or death.
程序性死亡 1（PD-1）检查点抑制剂（CKI）可导致免疫相关不良事件（irAE）。我们旨在评估非黑色素瘤恶性肿瘤中 irAE 的发生是否与治疗反应相关。
我们对在 Fox Chase 癌症中心接受抗 PD-1 CKI 单药治疗的患者进行了回顾性研究。终点包括总缓解率（ORR）、下一次治疗或死亡的时间（TTNTD）和总生存期（OS）。Fisher 确切检验和逻辑回归模型用于确定 irAE 发生率与 ORR 之间的关联，Kaplan-Meier 曲线和对数秩检验以及 Cox 回归模型用于比较 TTNTD 和 OS。
在 2011 年 11 月至 2016 年 11 月期间，有 160 名患者接受了> 1 剂抗 PD-1 CKI 的治疗。其中 73 名（46%）在临床试验中接受治疗。在 64 名（40%）患者中观察到免疫相关不良事件，其中 36 名（23%）需要使用类固醇。在 142 名可评估临床反应的患者中，28 名（20%）在首次扫描时获得部分缓解。在临床试验患者中观察到 irAE 与 ORR 之间存在关联（= 0.007），但在非试验患者中则没有（= 0.13）。当使用多变量分析控制临床试验参与和癌症类型时，低级别 irAE 具有更高的 ORR（= 0.017）和更长的 TTNTD（= 0.008）。irAE 发生率与 OS 之间未见关联（= 0.827）。需要类固醇治疗的 irAE 与增加的 TTNTD 呈边缘相关（= 0.05，风险比 0.62），但与 OS 无关（= 0.13）。
我们在接受 PD-1 CKI 治疗的非黑色素瘤患者中证明了 irAE 的发生与临床结局之间存在多种正相关，这需要进一步验证。
本研究评估了非黑色素瘤患者接受程序性细胞死亡 1 检查点抑制剂治疗后免疫相关不良事件的发生是否与改善的临床结局相关。结果表明，对于一部分患者，特别是那些患有低级别免疫相关不良事件的患者，免疫相关不良事件预示着缓解率提高和下一次治疗或死亡的时间延长。
