Journal Article

Comparison of zuberitamab plus CHOP versus rituximab plus CHOP for the treatment of drug-naïve patients diagnosed with CD20-positive diffuse large B-cell lymphoma: a phase 3 trial

Wang, Jishi, Zhu, Xiongpeng, Cheng, Ying, Shen, Jianzhen, Jiang, Wenqi, Zhou, Hui, Zhong, Meizuo, Zhang, Mingzhi, Yang, Wei, Yan, Feng, Sun, Xiuhua, Lv, Fangfang, Zhang, Qingyuan, Jin, Jie, Xiang, Ying, Song, Yuqin, Qian, Zhengzi, Wang, Zhao, Lin, Lie, Gao, Sujun, Zhang, Donghua, Guo, Qunyi, Liu, Lihong, Cen, Hong, Wang, Jingbo, He, Chuan, Xu, Bing, Yang, Haiyan, Yang, Yu, Huang, Yunhong, Liu, Huilan, Zhang, Mei, Zhang, Xiaohong, Li, Zhiming, Zhang, Weihua, Zhang, Liling, Feng, Ru, Yu, Ding, Zhou, Min, Li, Wenyu, Jing, Hongmei, Zhao, Weili, Zhao, Hongguo, Zhu, Jun

2024

Overview

BackgroundIn patients with untreated CD20-positive diffuse large B-cell lymphoma (DLBCL), a phase 3 trial was carried out to evaluate the efficacy and safety of zuberitamab plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; Hi-CHOP) versus rituximab plus CHOP (R-CHOP) treatment regimens.MethodsIn a 2:1 ratio, eligible patients were assigned randomly to receive treatment of six cycles of either 375 mg/m2 zuberitamab or rituximab together with conventional CHOP chemotherapy. The objective response rate (ORR) at C6D50 served as the primary endpoint, and a non-inferiority margin of 10% was established. The secondary endpoints included the complete response (CR) rate at C6D50, duration of response (DOR), progression-free survival (PFS) and event-free survival (EFS) judged by blinded-independent review committee (BIRC), overall survival (OS) and safety outcomes.ResultsOf the 487 randomized patients, 423 patients including 287 in the Hi-CHOP and 136 in the R-CHOP groups completed the C6D50 assessment. For the full analysis set (FAS) and per-protocol set (PPS), BIRC-assessed ORR at C6D50 for the Hi-CHOP and R-CHOP groups were 83.5% versus 81.4% and 95.3% versus 93.7%, respectively. The non-inferiority was confirmed as the lower limit of the two-sided 95% CI for the intergroup differences of −5.2% and −3.3%; both were >−10% in the FAS and PPS. The BIRC-assessed CR rate of Hi-CHOP was significantly higher in PPS (85.7% vs 77.3%, p=0.038), but comparable in FAS (75.2% vs 67.9%, p=0.092). After a median follow-up of 29.6 months, patients in the Hi-CHOP group had a slight advantage with regard to the DOR (HR 0.74, p=0.173), PFS (HR 0.67, p=0.057), EFS (HR 0.90, p=0.517) and OS (HR 0.60, p=0.059). Patients with the germinal-center B cell-like subtype who received Hi-CHOP exhibited statistically significant improvements in ORR (p=0.034) and CR rate (p=0.038) at C6D50, EFS (p=0.046) and OS (p=0.014). Treatment-emergent adverse event occurrence rates were comparable across groups (all p>0.05). Infusion-related responses occurred more often in the Hi-CHOP group (32.1% vs 19.9%, p=0.006), all of grade 1–3 severity.ConclusionsZuberitamab (375 mg/m2) plus CHOP was non-inferior to R-CHOP regarding ORR but exhibited a higher CR rate and was well tolerated in CD20-positive, previously untreated Chinese patients with DLBCL.Trial registration numberChinese Clinical Trial Registry, ChiCTR2000040602, retrospectively registered.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult / Aged / Amino acids / Antigens, CD20 - metabolism / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - pharmacology / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Chemotherapy / Clinical/translational cancer immunotherapy / Cyclophosphamide - administration & dosage / Cyclophosphamide - therapeutic use / Cytotoxicity / Doxorubicin - administration & dosage / Doxorubicin - adverse effects / Doxorubicin - therapeutic use / Drug dosages / Female / Granulocytes / Hematologic Malignancies / Humans / Immunotherapy / Lymphoma / Lymphoma, Large B-Cell, Diffuse - drug therapy / Male / Middle Aged / Monoclonal antibodies / Neutropenia / Oncology / Patients / Prednisone - administration & dosage / Prednisone - adverse effects / Prednisone - therapeutic use / Rituximab - administration & dosage / Rituximab - adverse effects / Rituximab - pharmacology / Rituximab - therapeutic use / Targeted cancer therapy / Vincristine - adverse effects / Vincristine - therapeutic use / Young Adult