泽布替尼联合R-CHOP方案治疗新诊断的双表达淋巴瘤：一项2期临床研究。

Zanubrutinib plus R-CHOP for the treatment of newly diagnosed double-expressor lymphoma: A phase 2 clinical study.

作者信息

Yin Xia, He Qiang, Liu Dan, Xie Linna, Wang Hui, Chen Chunyan, Zhao Chuanli, Shan Ningning, Shi Shanshan, Wei Haichen, Ma Ji, Lu Ke, Wang Liang, Wang Yan, Xing Lijie, Li Zengjun

机构信息

Department of Lymphoma, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China.

出版信息

Cancer. 2025 Jan 1;131(1):e35697. doi: 10.1002/cncr.35697.

BACKGROUND

Double-expressor lymphoma (DEL) has a poorer prognosis than other subtypes of diffuse large B-cell lymphoma (DLBCL). This study is a multicenter, prospective, single-arm, phase 2 clinical study initiated by investigators to evaluate the efficacy and safety of combined zanubrutinib with R-CHOP, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for patients with DEL (stage II or more), as well as to explore factors related to efficacy preliminarily.

METHODS

From November 2020 to July 2022, 48 newly diagnosed patients were enrolled. All patients received twice-daily oral zanubrutinib (160 mg) for 6 months and standardized R-CHOP regimen for six to eight cycles.

RESULTS

The objective response rate (ORR) was 89.6%, with a complete response rate (CRR) of 83.3%. The median follow-up was 29.3 months. The median progression-free survival (PFS) and overall survival (OS) were not reached. The PFS and OS were 81.25% and 93.75% at 2 years, respectively. Grade ≥3 adverse events (AEs) were reported in 23 of 48 (47.9%) patients. Next-generation sequencing (NGS) results of 33 patients showed that TP53, MYD88, and PIM1 were the most common mutated gene. Multivariate analysis revealed that BCL-6 gene rearrangement was an adverse prognostic factor for both PFS (hazard ratio [HR], 0.247; 95% confidence article [CI], 0.068-0.9; p = .034) and OS (HR, 0.057; 95% CI, 0.006-0.591; p = .016), whereas the number of extranodal involvements also significantly influenced OS (HR, 15.12; 95% CI, 1.07-213.65; p = .044).

CONCLUSIONS

Zanubrutinib in combination with R-CHOP is an effective option for DEL patients, and the toxicity of zanubrutinib is entirely acceptable for patients.

背景

双表达淋巴瘤（DEL）的预后比弥漫性大B细胞淋巴瘤（DLBCL）的其他亚型更差。本研究是一项由研究人员发起的多中心、前瞻性、单臂、2期临床研究，旨在评估泽布替尼联合R-CHOP（包括利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松）治疗DEL患者（II期或更晚期）的疗效和安全性，并初步探索与疗效相关的因素。

方法

2020年11月至2022年7月，共纳入48例新诊断患者。所有患者接受每日两次口服泽布替尼（160mg），持续6个月，并接受标准化的R-CHOP方案治疗6至8个周期。

结果

客观缓解率（ORR）为89.6%，完全缓解率（CRR）为83.3%。中位随访时间为29.3个月。中位无进展生存期（PFS）和总生存期（OS）尚未达到。2年时的PFS和OS分别为81.25%和93.75%。48例患者中有23例（47.9%）报告了≥3级不良事件（AE）。33例患者的二代测序（NGS）结果显示，TP53、MYD88和PIM1是最常见的突变基因。多变量分析显示，BCL-6基因重排是PFS（风险比[HR]，0.247；95%置信区间[CI]，0.068-0.9；p = 0.034）和OS（HR，0.057；95%CI，0.006-0.591；p = 0.016）的不良预后因素，而结外受累数量也显著影响OS（HR，15.12；95%CI，1.07-213.65；p = 0.044）。