PD-1/PD-L1抑制药联合化疗用药顺序对免疫相关不良反应的影响

Effect of Medication Sequence of PD-1/PD-L1 Inhibitor Combined with Chemotherapy on irAEs

目的:探讨程序性死亡蛋白-1/细胞程序性死亡蛋白配体1(PD-1/PD-L1)抑制药联合化疗的用药顺序,对免疫相关不良反应(irAEs)的影响。方法:收集某肿瘤专科医院2021年1~9月接受PD-1/PD-L1抑制药联合化疗药物治疗的200例病例,统计患者基本情况以及irAEs发生情况,并比较先使用PD-1/PD-L1抑制药再化疗的100例病例(后化疗组),与先化疗再使用PD-1/PD-L1抑制药的100例病例(先化疗组),发生irAEs的差异情况。结果:200例病例中男138例(69.0%),女62例(31.0%),年龄集中在40岁(72.5%);所患疾病主要为肺癌(28.5%)、肝癌(15.0%)和鼻咽癌(10.5%)。共发生irAEs 108例(54.0%),其中先化疗组irAEs发生率(64.0%)显著高于后化疗组的44.0%(P<0.05)。irAEs类型以肝脏毒性(14.5%)、皮肤毒性(11.0%)和内分泌毒性(9.5%)为主。毒性分级中G1G2有123例(61.5%),G3及以上7例(3.5%)。后化疗组中G1G2有51例,G3及以上4例;先化疗组中G~1G2有72例,G3及以上3例。88例患者发生1种类型的irAE,18例发生2种类型的irAE,2例发生3种类型的irAE。后化疗组与先化疗组发生≥2种类型irAEs的均为10例。结论:PD-1/PD-L1抑制药联合化疗治疗中,用药顺序与irAEs的发生密切相关,临床应加以重视。

Objective: To investigate the effect of administration sequence of PD-1/PD-L1 inhibitor combined with chemotherapy on immune-related adverse events(irAEs). Methods: Totally 200 patients received PD-1/PD-L1 inhibitor combined with chemotherapy from January to September 2021 in a tumor specialized hospital were searched, and half of them were first treated with PD-1/PD-L1 inhibitor followed by chemotherapy(post-chemotherapy group) and the other half were first treated with chemotherapy followed by PD-1/PD-L1 inhibitor(pre-chemotherapy group). The basic information of patients and the occurrence of immune-related adverse events were collected and statistically analyzed, and the difference in the occurrence of irAEs between the two groups was compared.Results: The case data of 200 tumor patients were collected, including 138 males(69.00%) and 62 females(31.00%) within the age range from 40 to 69 years old(72.50%). The diseases mainly included lung cancer(28.50%), liver cancer(15.00%) and nasopharyngeal carcinoma(10.50%). There were 108 cases of irAEs(54.00%), and the incidence of irAEs was related to the administration sequence(P<0.05). The incidence of irAEs(64.00%) in the pre-chemotherapy group was higher than that in the post-chemotherapy group(44.00%). The main types of irAEs were liver toxicity(14.50%), skin toxicity(11.00%) and endocrine toxicity(9.50%). There were 123 cases(61.50%) in G1-G2 of toxicity grading, and 7 cases(3.50%) in G3 and above of toxicity grading. Among them, 51 cases in G1-G2 and 4 cases in G3 and above were in the post-chemotherapy group, while 72 cases in G1-G2 and 3 cases in G3 and above were in the pre-chemotherapy group. Totally 88 cases had one type of irAEs, 18 cases had 2 types, and 2 cases had 3 types of irAEs. The number of patients with two or more types of irAEs in the post-chemotherapy group was the same as that in the pre-chemotherapy group, both were 10 cases. Conclusion: The order of administration is closely related to the occurrence of immune-related adverse events in the treatment with PD-1/PD-L1 inhibitor combined with hemotherapy, and more attention should be paid to it in clinical application.