PD-1抑制剂治疗复发或难治性经典型霍奇金淋巴瘤的疗效和安全性分析  

Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma

作　　者：山丹丹 刘慧敏 刘薇 黄文阳 吕瑞 邓书会 易树华 安刚 徐燕 隋伟薇 王婷玉 傅明伟 赵耀中 邱录贵 邹德慧 Shan Dandan;Liu Huimin;Liu Wei;Huang Wenyang;Lyu Rui;Deng Shuhui;Yi Shuhua;An Gang;Xu Yan;Sui Weiwei;Wang Tingyu;Fu Mingwei;Zhao Yaozhong;Qiu Lugui;Zou Dehui(State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China;Tianjin Institutes of Health Science,Tianjin 301600,China)

机构地区：[1]中国医学科学院血液病医院(中国医学科学院血液学研究所),实验血液学国家重点实验室,国家血液系统疾病临床医学研究中心,细胞生态海河实验室,天津300020 [2]天津医学健康研究院,天津301600

出　　处：《中华血液学杂志》2023年第7期555-560,共6页Chinese Journal of Hematology

摘　　要：目的回顾性分析程序性细胞死亡蛋白-1(programmed cell death protein-1,PD-1)抑制剂单药或联合化疗治疗复发或难治性经典型霍奇金淋巴瘤(R/R cHL)的疗效和安全性。方法共纳入2016年9月至2020年12月就诊于中国医学科学院血液病医院的35例R/R cHL患者,其中17例给予PD-1抑制剂单药治疗,另18例接受PD-1抑制剂联合化疗。回顾性分析其临床资料和随访数据,采用Kaplan-Meier法和Cox比例风险模型进行生存分析。结果35例R/R cHL患者中位年龄29(11~61)岁,男性占54.3%,62.9%的患者Ann Arbor分期为进展期,48.6%伴有结外侵犯。PD-1抑制剂治疗前的中位治疗线数为2(1~3)线。28例患者获得客观缓解[其中22例为完全缓解(CR)],客观缓解率(ORR)和CR率分别为80.0%和62.9%;其中PD-1单药治疗组的ORR和CR率分别为64.7%和58.8%,PD-1联合化疗组的ORR和CR率分别为94.4%和66.7%。18例[13例CR和5例部分缓解(PR)]患者序贯自体造血干细胞移植(auto-HSCT)治疗,其中8例患者auto-HSCT后给予PD-1抑制剂单药巩固治疗;移植后患者均获得并维持CR状态,与未序贯auto-HSCT的患者相比无进展生存(PFS)率显著升高(4年PFS率分别为100%和53.5%,P=0.041)。免疫相关的不良事件发生率为29%,仅1例患者出现≥3级不良反应,整体安全性良好。结论PD-1抑制剂治疗R/R cHL安全、有效,PD-1抑制剂联合化疗显著提高缓解率。对于挽救治疗敏感的患者,auto-HSCT巩固治疗进一步改善长期生存。Objective This retrospective,single-center study aimed to evaluate the efficacy and safety of programmed death-1(PD-1)inhibitors,either as monotherapy or in combination with chemotherapy,in the management of relapse/refractory classical Hodgkin's lymphoma(R/R cHL).Methods A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College from September 2016 to December 2020 were enrolled in this study.Among them,17 patients received PD-1 inhibitor monotherapy(PD-1 inhibitor group),while 18 patients received a combination of PD-1 inhibitor and chemotherapy(PD-1 inhibitor+chemotherapy group).Clinical data and follow-up information were retrospectively analyzed,and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model.Results The median age of the 35 patients with R/R cHL was 29 years(range:11-61 years),with 54.3%being male.According to the Ann Arbor staging system,62.9%of patients presented with advanced(stageⅢ/Ⅳ)disease,and 48.6%had extranodal involvement.Before PD-1 inhibitor therapy,the median number of prior lines of therapy was 2(range:1-3).Objective responses were observed in 28 patients,including 22 complete response(CR)cases,resulting in an overall response rate(ORR)of 80.0%and a CR rate of 62.9%.Specifically,the ORR and CR rates were 64.7%and 58.8%,respectively,in the PD-1 inhibitor group and 94.4%and 66.7%,respectively,in the PD-1 inhibitor+chemotherapy group.Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation(auto-HSCT)[13 CR and five partial response(PR)cases],eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy.All patients maintained a CR status after transplantation,and they exhibited significantly improved progression-free survival(PFS)rates compared with those who did not undergo sequential auto-HSCT(4-year PFS rates:100%vs 53.5%;P=0.041).The incidence of imm

关 键 词：程序性细胞死亡蛋白-1抑制剂 复发或难治 经典型霍奇金淋巴瘤 

分 类 号：R733.1[医药卫生—肿瘤]