泊洛妥珠单抗联合利妥昔单抗、环磷酰胺、多柔比星和泼尼松用于初治弥漫性大B细胞淋巴瘤的疗效与安全性：一项真实世界、多中心、回顾性队列研究

Efficacy and Safety of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin and Prednisone for Previously Untreated Diffuse Large B-Cell Lymphoma: A Real-World, Multi-Center, Retrospective Cohort Study.

作者信息

Zhao Peiqi, Zhao Shu, Huang Chen, Li Yajun, Wang Jiesong, Xu Junqing, Li Lanfang, Qian Zhengzi, Li Wei, Zhou Shiyong, Qiu Lihua, Liu Xianming, Chen Ying, Jiang Yanan, Zheng Yanbin, Chen Daoguang, Zhou Hui, Gao Yuhuan, Zhang Qingyuan, Zhang Huilai

机构信息

Department of Lymphoma, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.

出版信息

Hematol Oncol. 2025 Jan;43(1):e70017. doi: 10.1002/hon.70017.

DOI:10.1002/hon.70017

PMID:39641321

Abstract

Polatuzumab vedotin plus R-CHP (Pola-R-CHP) is approved as a new standard first-line therapy for diffuse large B-cell lymphoma (DLBCL) based on the POLARIX trial. However, real-world data on its efficacy and safety in unselected patients is lacking. We conducted a retrospective cohort study to evaluate Pola-R-CHP versus R-CHOP outcomes in routine clinical practice in China. This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of polatuzumab vedotin up until February 2024. A total of 600 eligible patients from 6 centers were identified, 131 receiving Pola-R-CHP and 469 R-CHOP. After 1:2 propensity score matching, 128 pairs were obtained for further survival and prognosis analysis. With a median follow-up of 12.8 months, 12-month progression-free survival (PFS) was numerically higher with Pola-R-CHP versus R-CHOP (90.3% vs. 84.1%, p = 0.18). Benefits were consistently observed across molecular subgroups, especially advanced stage, ECOG ≥ 2, extranodal involvement ≥ 2 and non-GCB group. The complete response rate of the Pola-R-CHP group was higher than that of the RCHOP group (86.8% vs. 79.7%; p = 0.09), but there was no statistical difference. Safety profiles were comparable, with no new concerns. Among 128 patients treated with Pola-R-CHP, 96 underwent gene sequencing analysis: MCD (25.0%), EZB (13.5%), combined subtype (12.5%), ST2 (9.4%), and other/unclassifiable subtype (30.2%). The most common mutations (> 25% of cases) were PIM1, TP53, BCL-6, KMT2D, SOCS1, BCL-2. Genetic testing results show the correlation between genotyping, gene mutations in PIM1/TP53 and therapeutic efficacy. This large real-world study supports Pola-R-CHP as an effective frontline option for DLBCL, with sustained efficacy versus R-CHOP observed in unselected populations. While 12-month PFS failed to reach statistical significance, subgroup analyses favor Pola-R-CHP. Further research with a wider population, longer follow-up, and screening of advantageous groups are warranted.

摘要

基于POLARIX试验，泊洛妥珠单抗维泊妥珠单抗联合R-CHP（Pola-R-CHP）被批准作为弥漫性大B细胞淋巴瘤（DLBCL）的新标准一线治疗方案。然而，目前缺乏其在未经选择的患者中的疗效和安全性的真实世界数据。我们进行了一项回顾性队列研究，以评估在中国常规临床实践中Pola-R-CHP与R-CHOP的治疗效果。这是一项多机构回顾性队列研究，纳入了截至2024年2月接受至少一剂泊洛妥珠单抗维泊妥珠单抗的所有连续患者。共确定了来自6个中心的600例符合条件的患者，其中131例接受Pola-R-CHP治疗，469例接受R-CHOP治疗。经过1:2倾向评分匹配后，获得128对患者进行进一步的生存和预后分析。中位随访12.8个月，Pola-R-CHP组的12个月无进展生存期（PFS）在数值上高于R-CHOP组（90.3%对84.1%，p = 0.18）。在各个分子亚组中均观察到益处，尤其是晚期、ECOG≥2、结外受累≥2和非生发中心B细胞（GCB）组。Pola-R-CHP组的完全缓解率高于RCHOP组（86.8%对79.7%；p = 0.09），但无统计学差异。安全性特征相当，没有新的问题。在接受Pola-R-CHP治疗的128例患者中，96例进行了基因测序分析：MCD（25.0%）、EZB（13.5%）、联合亚型（12.5%）、ST2（9.4%）和其他/无法分类的亚型（30.2%）。最常见的突变（>25%的病例）为PIM1、TP53、BCL-6、KMT2D、SOCS1、BCL-2。基因检测结果显示基因分型、PIM1/TP53基因突变与治疗疗效之间的相关性。这项大型真实世界研究支持Pola-R-CHP作为DLBCL的一种有效一线治疗选择，在未经选择的人群中与R-CHOP相比具有持续疗效。虽然12个月的PFS未达到统计学显著性，但亚组分析支持Pola-R-CHP。有必要进行更广泛人群、更长随访时间和优势人群筛查的进一步研究。