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 (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% vs 53.5% ; P=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. Conclusions: 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.
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。.
Keywords: Hodgkin’s lymphoma; PD-1 inhibitor; relapsed/refractory.