Shan D D, Liu H M, Liu W, Huang W Y, Lyu R, Deng S H, Yi S H, An G, Xu Y, Sui W W, Wang T Y, Fu M W, Zhao Y Z, Qiu L G, Zou D H
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.
Zhonghua Xue Ye Xue Za Zhi. 2023 Jul 14;44(7):555-560. doi: 10.3760/cma.j.issn.0253-2727.2023.07.005.
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) . 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. 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 (stage Ⅲ/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% 53.5% ; =0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.
这项回顾性单中心研究旨在评估程序性死亡受体 1（PD-1）抑制剂单药治疗或与化疗联合治疗复发/难治性经典型霍奇金淋巴瘤（R/R cHL）的疗效和安全性。2016年9月至2020年12月期间在中国医学科学院血液病医院、北京协和医学院接受治疗的35例R/R cHL患者纳入本研究。其中，17例患者接受PD-1抑制剂单药治疗（PD-1抑制剂组），18例患者接受PD-1抑制剂与化疗联合治疗（PD-1抑制剂+化疗组）。对临床资料和随访信息进行回顾性分析，并采用Kaplan-Meier法和Cox比例风险模型进行生存分析。35例R/R cHL患者的中位年龄为29岁（范围：11-61岁），男性占54.3%。根据Ann Arbor分期系统，62.9%的患者为晚期（Ⅲ/Ⅳ期）疾病，48.6%的患者有结外受累。在接受PD-1抑制剂治疗前，既往治疗的中位疗程数为2（范围：1-3）。28例患者观察到客观缓解，其中22例为完全缓解（CR），总缓解率（ORR）为80.0%，CR率为62.9%。具体而言，PD-1抑制剂组的ORR和CR率分别为64.7%和58.8%，PD-1抑制剂+化疗组分别为94.4%和66.7%。在18例接受序贯自体造血干细胞移植（auto-HSCT）的患者中（13例CR和5例部分缓解[PR]），8例患者在auto-HSCT后接受PD-1抑制剂治疗作为巩固治疗。所有患者移植后均维持CR状态，与未接受序贯auto-HSCT的患者相比，其无进展生存期（PFS）率显著提高（4年PFS率：100%对53.5%；P=0.041）。免疫相关不良事件的发生率为29%，仅有1例患者发生≥3级不良反应，表明该治疗方法具有良好的安全性。PD-1抑制剂单药治疗在R/R cHL患者中显示出显著疗效和持续缓解。PD-1抑制剂与化疗联合可显著提高缓解率。此外，对于挽救治疗敏感的患者，auto-HSCT后用PD-1抑制剂进行巩固治疗具有延长PFS的潜力。
