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

• Published in: Hematological oncology 2025-01, Vol.43 (1), p.e70017
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Doxorubicin - therapeutic use; Female; Humans; Immunoconjugates; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Middle Aged; Prednisone - administration & dosage; Prednisone - adverse effects; Prednisone - therapeutic use; Retrospective Studies; Rituximab - administration & dosage; Rituximab - adverse effects; Rituximab - therapeutic use; Survival Rate; Vincristine - administration & dosage; Vincristine - adverse effects; Vincristine - therapeutic use; Young Adult
• ISSN: 1099-1069; 1099-1069
• DOI: 10.1002/hon.70017

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.