特瑞普利单抗致转移性恶性黑色素瘤超进展的临床分析  

Clinical analysis of hyperprogression of metastatic malignant melanoma induced by toripalimab

作　　者：段荣 唐碧霞[1] 李思明[1] 鄢谢桥 盛锡楠[1] 崔传亮[1] 斯璐[1] 周莉[1] 毛丽丽[1] 连斌[1] 王轩[1] 白雪[1] 许华艳 齐忠慧 李彩莉 郭军[1] 迟志宏[1] Duan Rong;Tang Bixia;Li Siming;Yan Xieqiao;Sheng Xinan;Cui Chuanliang;Si Lu;Zhou Li;Mao Lili;Lian Bin;Wang Xuan;Bai Xue;Xu Huayan;Qi Zhonghui;Li Caili;Guo Jun;Chi Zhihong(Department of Kidney Cancer and Melanoma,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Beiijng Cancer Hospital and Beijing Institute for Cancer Research,Beijing 100142,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所肾癌黑色素瘤内科,恶性肿瘤发病机制及转移研究教育部重点实验室,北京100142

出　　处：《药物不良反应杂志》2020年第10期553-558,共6页Adverse Drug Reactions Journal

基　　金：国家自然科学基金(81672696)。

摘　　要：目的探讨特瑞普利单抗(JS001)致转移性恶性黑色素瘤超进展的发生情况和临床特点。方法收集2018年2月至2019年9月在北京大学肿瘤医院肾癌黑色素瘤内科接受JS001单药或联合其他抗肿瘤药物治疗的转移性恶性黑色素瘤患者,从中筛选出发生超进展的患者作为病例组,并根据病例组患者的基线年龄、性别、美国东部肿瘤协作组评分、原发灶位置、乳酸脱氢酶(LDH)升高水平等按1∶4的比例匹配无超进展证据者作为对照组。比较2组患者的临床特点及预后,并对病例组的超进展情况进行描述性分析。结果共收集到130例接受JS001单药或联合其他抗肿瘤药物治疗的转移性恶性黑色素瘤患者,其中8例(男性5例,女性3例,年龄41~68岁)发生肿瘤超进展(病例组),肿瘤超进展发生率为6.15%。根据病例组患者基线特征匹配32例未发生肿瘤超进展者为对照组。病例组基线时肿瘤转移脏器超过2个者占比明显高于对照组[6/8比21.9%(7/32),P=0.014],LDH水平与治疗前相比明显升高[(965±710)U/L比(264±64)U/L,P=0.025],无疾病进展生存期和总生存期均明显短于对照组[1.7(95%置信区间:1.4~2.0)个月比3.1(95%置信区间:2.7~3.5)个月,P<0.001;4.8(95%置信区间:0~11.2)个月比10.7(95%置信区间:10.4~10.9)个月,P=0.031]。结论转移性恶性黑色素瘤患者在JS001治疗初期可发生肿瘤超进展,治疗前转移脏器超过2个者更易发生;发生肿瘤超进展的患者预后较差。监测血清LDH水平可能有助于及早发现肿瘤超进展。Objective To explore the occurrence and clinical characteristics of hyperprogression of metastatic malignant melanoma caused by toripalimab(JS001).Methods The medical records of patients with metastatic malignant melanoma treated with JS001 alone or in combination with other antineo⁃plastic agents between February 2018 and September 2019 in Department of Kidney Cancer and Melanoma of Beijng Cancer Hospital were collected.Patients displaying hyperprogression were screened into the case group,who were matched with those without hyperprogression evidence(the control group)in a 1/4 ratio according to baseline age,gender,Eastern Cooperative Oncology Group score,location of the primary lesion,and elevated level of lactate dehydrogenase(LDH).The clinical characteristics and prognosis of patients between the 2 groups were compared and the hyperprogression in the case group was analyzed descriptively.Results A total of 130 patients with metastatic malignant melanoma who received JS001 alone or in combi⁃nation with other antineoplastic agents were collected.Hyperprogression occurred in 8 patients(the case group),including 5 males and 3 females,aged(52.5±8.5)years.The incidence of hyperprogression was 6.15%.Thirty⁃two patients without displaying hyperprogression were matched as the control group according to the baseline characteristics of patients in the case group.Patients with metastatic lesions in more than 2 organs at baseline in the case group were significantly more than those in the control group(6/8 vs.7/32,P=0.014);the LDH level of patients in the case group significantly increased after treatment than before[(965±710)U/L vs.(264±64)U/L,P=0.025];the progression⁃free survival and overall survival in patients were significantly lower than those of patients in the control group[1.7(95%CI:1.4-2.0)months vs.3.1(95%CI:2.7-3.5)months,P<0.001;4.8(95%CI:0⁃11.2)months vs.10.7(95%CI:10.4-10.9)months,P=0.031].Conclusions Patients with melanoma may experience hyperprogression in early stages of JS001 treatment.Pat

关 键 词：黑色素瘤 抗肿瘤药物 免疫性 程序性细胞死亡1受体 超进展 

分 类 号：R739.5[医药卫生—肿瘤]