Impact of aging on immune-related adverse events generated by anti-programmed death (ligand)PD-(L)1 therapies
Impact of aging on immune-related adverse events generated by anti-programmed death (ligand)PD-(L)1 therapies
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DOI：
10.1016/j.ejca.2020.01.013
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发表时间：
2020-04-01
影响因子：
8.4
通讯作者：
Marabelle, Aurelien
中科院分区：
文献类型：
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作者：
Baldini, Capucine;Romano, Patricia Martin;Marabelle, Aurelien
背景：衰老是癌症的重要危险因素，与预后不良有关。免疫系统的虚弱，也称为免疫衰老，可能会随着年龄的增长而发生。衰老对免疫检查点阻滞剂，如抗程序性死亡(配体)PD-(L)1的疗效和安全性的影响仍不确定。本研究旨在评估免疫相关不良事件(IrAEs)在70岁及以上患者中的发生率。方法：将2014年6月至2017年10月在Gustave Roussy接受抗PD(L)1单一疗法治疗的晚期实体肿瘤患者前瞻性纳入专门的irAEs药物警戒注册登记REISAMIC(Registre des Effets Indesirable Serves des Anticorps monclane x免疫调节器en Cancerologie)。采用卡方检验比较70岁以上患者(老年患者，OP)和70岁患者(年轻患者，YP)之间>；II级irAEs的发生率。结果：在接受抗PD治疗(L)的603例患者中，191例为70岁(OP)，424例为70岁(YP)。OP和YP的中位(范围)年龄分别为77岁(70-93岁)和59岁(17-69岁)。这些患者中共有165例发生irAEs(103例II级和58例III-IV级)。OP组总的>；=II级irAEs发生率高于yP组(33%比25%，P=0.03)。此外，OP组较YP组更容易出现多个irAEs(p=0.037)。OP组皮肤毒性发生率高于YP组(p=0.007)，而内分泌毒性发生率低于YP组(p=0.044)。这种较高水平的irAEs似乎是OP患者停药率较高的原因(p=0.2)。结论：尽管抗PD-(L)1免疫疗法仍然是老年患者可以接受的治疗方案，但处方人员应该意识到irAEs在老年患者中更常见。为了更好地理解衰老和irAEs之间的关系，有必要进行进一步的翻译研究。(C)2020年由爱思唯尔有限公司出版。
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 Indesirables Severes des Anticorps Monoclonaux Immunomodulateurs en Cancerologie). 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. (C) 2020 Published by Elsevier Ltd.