Qin Y, Zhao F Y, Zhou Y, Jiang S Y, Yang S, Shi Y K
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Zhonghua Zhong Liu Za Zhi. 2020 Dec 23;42(12):1034-1039. doi: 10.3760/cma.j.cn112152-20200506-00410.
To investigate the efficacy and safety of programmed cell death protein-1 (PD-1) inhibitor combined with rituximab in the treatment of refractory or relapsed diffuse large B-cell lymphoma (rrDLBCL) patients. The efficacy and safety of rrDLBCL patients treated with PD-1 inhibitor combined with rituximab as salvage therapeutic regimen after initially treated with rituximab, cyclophosphamide, anthracycline, vincristine and prednisone (R-CHOP) regimen in Cancer Hospital, Chinese Academy of Medical Science & Peking Union Medical College from October 2018 to Janurary 2020 were retrospectively analyzed.Patient who received at least one dose of PD-1 inhibitor combined with rituximab treatment and obtained the efficacy and safety evaluation were included. A total of 22 patients were enrolled in this study. The median age was 51.5 years and the median number of prior treatment regimen was 2. The median time to progression (TTP) for the initial R-CHOP treatment was 9.3 months and the median interval time of rituximab administrations between the previous and the research regimen was 5.5 months. Patients were classified as germinal center B cell (GCB) origin (=8), non-GCB origin (=9) and primary mediastinal large B cell lymphoma (PMBCL, =5). Four patients were double-expression lymphoma, one patient were triple-hit lymphoma. Nine patients had PD-L1 immunohistochemical staining and the proportion of PD-L1 positive tumor cells were 1%-90% for eight patients and negative for one patient.The objective response rate (ORR) and complete response rate (CR) were 72.7% (16/22) and 13.6% (3/22), respectively. The median progression free survival (PFS) was 8.0 (95% 7.0-14.5) months, and overall survival (OS) was not reached. For the 17 patients of non-specific DLBCL, the ORR was 64.7% (11/17), the estimated median PFS was 4.0 (95% 0-8.8) months, the 1-year PFS and OS rates were 39.2% (95% 19.4%-43.4%)and 81.3% (95%: 71.4%-91.1%), respectively. All of 5 PMBCL cases achieved ORR, among them, one case was CR and 4 cases were partial responase (PR), and their PFS were 16.4, 9.3, 8.3, 7.9and 3.0 months, respectively. One patient had National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 grade 3 hypophysitis and one patient had NCI CTCAE grade 3 interstitial pneumonia. For rrDLBCL patients who have underwent rituximab treatment previously, PD-1 inhibitor combined with rituximab regimen shows a promising efficacy and tolerability, which can be a potential treatment option.
探讨程序性细胞死亡蛋白1（PD-1）抑制剂联合利妥昔单抗治疗难治性或复发性弥漫性大B细胞淋巴瘤（rrDLBCL）患者的疗效及安全性。回顾性分析2018年10月至2020年1月在中国医学科学院肿瘤医院、北京协和医学院接受利妥昔单抗、环磷酰胺、蒽环类药物、长春新碱和泼尼松（R-CHOP）方案初始治疗后，采用PD-1抑制剂联合利妥昔单抗作为挽救治疗方案的rrDLBCL患者的疗效及安全性。纳入接受至少一剂PD-1抑制剂联合利妥昔单抗治疗并获得疗效及安全性评估的患者。本研究共纳入22例患者。中位年龄为51.5岁，既往治疗方案的中位次数为2次。初始R-CHOP治疗的中位疾病进展时间（TTP）为9.3个月，既往治疗方案与本研究方案之间利妥昔单抗给药的中位间隔时间为5.5个月。患者分为生发中心B细胞（GCB）来源（=8例）、非GCB来源（=9例）和原发性纵隔大B细胞淋巴瘤（PMBCL，=5例）。4例为双表达淋巴瘤，1例为三打击淋巴瘤。9例患者进行了PD-L1免疫组化染色，8例患者PD-L1阳性肿瘤细胞比例为1%-90%，1例患者为阴性。客观缓解率（ORR）和完全缓解率（CR）分别为72.7%（16/22）和13.6%（3/22）。中位无进展生存期（PFS）为8.0（95%CI 7.0-14.5）个月，总生存期（OS）未达到。对于17例非特异性DLBCL患者，ORR为64.7%（11/17），估计中位PFS为4.0（95%CI 0-8.8）个月，1年PFS率和OS率分别为39.2%（95%CI 19.4%-43.4%）和81.3%（95%CI：71.4%-91.1%）。5例PMBCL患者均达到ORR，其中1例为CR，4例为部分缓解（PR），其PFS分别为16.4、9.3、8.3、7.9和3.0个月。1例患者发生美国国立癌症研究所不良事件通用术语标准（NCI CTCAE）第5.0版3级垂体炎，1例患者发生NCI CTCAE 3级间质性肺炎。对于既往接受过利妥昔单抗治疗的rrDLBCL患者，PD-1抑制剂联合利妥昔单抗方案显示出有前景的疗效和耐受性，可作为一种潜在的治疗选择。
