经治恶性胸膜间皮瘤免疫联合治疗临床分析

Clinical analysis of combined immunotherapy in patients with malignant pleural mesothelioma

目的探讨真实世界中经治恶性胸膜间皮瘤(MPM)患者接受免疫联合治疗的现状、疗效及安全性。方法收集2016—2021年中国医学科学院肿瘤医院和北京大学首钢医院39例经治MPM患者的临床病理资料,中位随访18.97个月,根据应用免疫检查点抑制剂(ICIs)治疗的情况分为免疫治疗组(19例)和对照组(20例),分析免疫联合治疗的疗效及安全性。生存分析采用Kaplan-Meier法,生存率的比较采用Log rank检验。结果免疫治疗组和对照组的客观缓解率(ORR)分别为21.1%和10.0%,疾病控制率(DCR)分别为78.9%和55.0%,差异均无统计学意义(均P>0.05)。免疫治疗组中位总生存时间(OS)长于对照组(分别为14.53和7.07个月,P=0.015),但两组的中位无进展生存时间(PFS)差异无统计学意义(4.80和2.03个月,P=0.062)。单因素分析显示,胸腔积液性质、病理亚型及免疫治疗疗效与MPM患者的PFS和OS均有关(均P<0.05)。免疫治疗组不良反应发生率为89.5%(17/19),最常见的不良反应为血液学毒性(9例),其次为恶心呕吐(7例)、疲劳(6例)和皮肤损害(6例)。有5例患者出现免疫治疗相关不良反应,均为1~2级。结论真实世界中,MPM患者多于后线开始接受免疫联合治疗,以联合化疗为主,中位治疗线数为二线。无论与化疗还是抗血管生成治疗联合均有较好的疗效,不良反应可控,具有良好的临床应用价值。

Objective To observe the present situation,efficacy and safety of immunotherapy in patients with malignant pleural mesothelioma(MPM).Methods The data of 39 patients with MPM in two centers from 2016 to 2021 were collected and the efficacy and safety were evaluated.According to the application of immune checkpoint inhibitors(ICIs),these patients,whose median clinical follow-up amounting to 18.97 months,were divided into immunotherapy group(19 cases)and control group(20 cases).Kaplan-Meier method and Log-rank test were used for the survival analysis.Results The objective response rate(ORR)and the disease control rate(DCR)in the immunotherapy group is 21.05%and 79.0%respectively,compared with 10.0%and 55.0%in the control group;and the difference was not statistically significant(P>0.05).The median overall survival(OS)in the immunotherapy group was significantly longer than that in the control group(14.53 months vs 7.07 months,P=0.015),but there was no significant difference in the median progression free survival(PFS)between two groups(4.80 months vs 2.03 months,P=0.062).Single factor survival analysis showed that the nature of pleural effusion,pathological subtype and the efficacy of immunotherapy were related to both PFS and OS of the patients with MPM(P<0.05).The incidence of adverse reactions in immunotherapy group was 89.5%(17 out of 19 cases),and the most common adverse event was hematological toxicity(9 cases),followed by nausea and vomiting(7 cases),fatigue(6 cases)and skin damage(6 cases).Five patients had immune checkpoint inhibitors(ICIs)related adverse reactions with grade 1-2.Conclusions Patients with MPM have begun to receive immunotherapy in more than 2-line mainly combined chemotherapy in the real world,and the median treatment line is 2-line.Either combined with chemotherapy or anti-angiogenesis therapy,ICI inhibitors have significant efficacy,controllable adverse events and good clinical value.