Deng Lijuan, Song Yuqin, Zhou Keshu, Li Dengju, Hu Jianda, Zou Dehui, Gao Sujun, Yang Haiyan, Zhang Huilai, Ji Jie, Xu Wei, Feng Ru, Jin Jie, Lv Fangfang, Fang Cheng, Xu Sheng, Zhu Jun
Department of Lymphoma, Peking University Cancer Hospital & Institute (Beijing Cancer Hospital), No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Adv Ther. 2025 Jun;42(6):2937-2949. doi: 10.1007/s12325-025-03202-x. Epub 2025 May 3.
Our previous study has suggested a favorable progression-free survival (PFS) with zanubrutinib over orelabrutinib in patients with relapsed or refractory mantle cell lymphoma (R/R MCL). Here, we conducted an updated analysis to indirectly compare the long-term efficacy between zanubrutinib and orelabrutinib in patients with R/R MCL.
Individual patient data from the zanubrutinib study were adjusted to match the patient population profile of the orelabrutinib study. An unanchored matching-adjusted indirect comparison (MAIC) was performed to adjust for effect modifiers and prognostic variables. The efficacy outcomes included investigator-assessed PFS, overall survival (OS), and overall response rate (ORR). Response evaluations were only computed tomography (CT)-based assessments in the orelabrutinib study, while positron emission tomography (PET)- and CT-based assessment were both performed in the zanubrutinib study. The comparison of PFS assessed by CT between zanubrutinib and orelabrutinib was the primary result.
After matching, the baseline characteristics were balanced between zanubrutinib and orelabrutinib, with an effective sample size of 70 in the zanubrutinib study. PFS assessed by CT was significantly longer in the zanubrutinib study vs. the orelabrutinib study (median PFS, not reached vs. 22.0 months; hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.34-0.86; P = 0.009). With longer follow-up, OS continued to trend favorably for zanubrutinib, with OS rate at 24 months numerically higher (83.7% vs. 74.3%); no statistical difference was observed (HR 0.68, 95% CI 0.36-1.27; P = 0.223). ORR was numerically higher in the zanubrutinib study (85.5% vs. 82.1%; odds ratio 1.28, 95% CI 0.56-2.94; P = 0.556).
MAIC results demonstrated that zanubrutinib had significantly longer PFS compared with orelabrutinib in the treatment of patients with R/R MCL.
我们之前的研究表明，在复发或难治性套细胞淋巴瘤（R/R MCL）患者中，泽布替尼的无进展生存期（PFS）优于奥雷巴替尼。在此，我们进行了一项更新分析，以间接比较泽布替尼和奥雷巴替尼在R/R MCL患者中的长期疗效。
对泽布替尼研究中的个体患者数据进行调整，以匹配奥雷巴替尼研究的患者人群特征。进行了无锚定匹配调整间接比较（MAIC），以调整效应修饰因素和预后变量。疗效结果包括研究者评估的PFS、总生存期（OS）和总缓解率（ORR）。在奥雷巴替尼研究中，缓解评估仅基于计算机断层扫描（CT），而在泽布替尼研究中则同时进行了正电子发射断层扫描（PET）和基于CT的评估。泽布替尼和奥雷巴替尼之间基于CT评估的PFS比较是主要结果。
匹配后，泽布替尼和奥雷巴替尼的基线特征达到平衡，泽布替尼研究中的有效样本量为70。与奥雷巴替尼研究相比，泽布替尼研究中基于CT评估的PFS显著更长（中位PFS，未达到 vs. 22.0个月；风险比[HR] 0.54，95%置信区间[CI] 0.34 - 0.86；P = 0.009）。随着随访时间延长，泽布替尼的OS继续呈有利趋势，24个月时的OS率在数值上更高（83.7% vs. 74.3%）；未观察到统计学差异（HR 0.68，95% CI 0.36 - 1.27；P = 0.223）。泽布替尼研究中的ORR在数值上更高（85.5% vs. 82.1%；优势比1.28，95% CI 0.56 - 2.94；P = 0.556）。
MAIC结果表明，在治疗R/R MCL患者时，泽布替尼的PFS显著长于奥雷巴替尼。
