Background

Aging is an important risk factor for cancers and is associated with poor prognosis. Weakness of the immune system, also called immunosenescence may occur with older age. The impact of aging on efficacy and safety of immune checkpoint blockers, such as anti-programmed death (ligand) PD-(L)1, remains undetermined. This study aims to evaluate the incidence of immune-related adverse events (irAEs) in patients aged 70 years or older than their younger counterparts.

Methods

Patients with advanced solid tumors treated at Gustave Roussy with an anti–PD-(L)1 monotherapy between June 2014 and October 2017 were prospectively included within the dedicated irAEs pharmacovigilance registry REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie). The incidence of irAEs of grade ≥II was compared between patients aged ≥70 (old patients, OP) versus patients aged < 70 years (young patients, YP) using a chi-squared test. Survivals were estimated using the Kaplan-Meier method.

Results

Among the 603 patients treated by anti-PD(L)1, 191 were ≥70 y.o (OP) and 424 < 70 y.o (YP). The median (range) age of OP and YP were respectively 77 (70–93) and 59 years old (17–69). A total of 165 irAEs occurred in these patients (103 grade II and 58 grade III–IV). The overall incidence of grade ≥II irAEs was higher in OP than in YP (33% versus 25%, p = 0.03). In addition, OP were more prone of having multiples irAEs compared with YP (p = 0.037). Skin toxicities were more frequent in OP than in YP (p = 0.007) but endocrine toxicities were less frequent in OP than in YP (p = 0.044). This higher level of irAEs seems to be responsible for a higher rate of treatment discontinuation in OP (p = 0.2). There was no statistical difference in median time to toxicity, exposure to steroids or survival between the two groups.

Conclusion

Although anti-PD-(L)1 immunotherapies remain an acceptable treatment option for older patients, prescribers should be aware that irAEs are more frequent in the elderly. Further translational studies are warranted to better understand the relationship between aging and irAEs.

中文翻译：

---

衰老对抗编程死亡（配体）PD-（L）1治疗产生的免疫相关不良事件的影响

背景

衰老是癌症的重要危险因素，并且与不良预后有关。免疫系统的衰弱，也称为免疫衰老，可能随着年龄的增长而发生。衰老对免疫检查点阻滞剂（例如抗程序性死亡（配体）PD-（L）1）的功效和安全性的影响尚未确定。这项研究旨在评估70岁以上年龄段的年轻患者的免疫相关不良事件（irAE）的发生率。

方法

于2014年6月至2017年10月之间在古斯塔夫·鲁西（Gustave Roussy）接受抗PD-（L）1单药治疗的晚期实体瘤患者，已被纳入专门的irAEs药物警戒注册中心REISAMIC（注册后的EffetsIndésirables塞维耶尔des Anticorps Monoclonaux Immunomodulateurs enCancérologie）。使用卡方检验比较了≥70岁的患者（老年患者，OP）和<70岁的患者（年轻患者，YP）中≥II级的irAEs的发生率。使用Kaplan-Meier方法估算存活率。

结果

在接受抗PD（L）1治疗的603例患者中，有191例≥70岁（OP）和424≤70岁（YP）。OP和YP的中位年龄范围分别为77岁（70-93）和59岁（17-69）。这些患者共发生了165例irAE（II级103例，III-IV级58例）。OP中≥II irAEs的总发生率高于YP（33％对25％，p = 0.03）。此外，与YP相比，OP更倾向于具有多个irAE（p = 0.037）。OP中的皮肤毒性比YP更常见（p = 0.007），但OP的皮肤内分泌毒性不如YP（p = 0.044）。较高的irAEs似乎是导致OP停药率更高的原因（p = 0.2）。两组之间的中毒时间，类固醇暴露时间或生存时间无统计学差异。

结论

尽管抗PD-（L）1免疫疗法仍然是老年患者可接受的治疗选择，但开药者应意识到，irAE在老年人中更为常见。有必要进行进一步的翻译研究，以更好地了解衰老与irAE之间的关系。