Munir Talha, Martinez-Calle Nicolás, Xu Sheng, Yang Keri, Ge Xiaoyun, Ali Ayad K, Mohseninejad Leyla, Dobi Balázs, Rakonczai Pal, Ma Han, Williams Rhys, Aldairy Wassim, Lamanna Nicole
Leeds Teaching Hospitals NHS Trust, Leeds, UK.
St James's Hospital, Beckett St, Harehills, Leeds, LS9 7TF, UK.
Oncol Ther. 2025 Sep 13. doi: 10.1007/s40487-025-00380-0.
Compared with chemoimmunotherapy, both zanubrutinib monotherapy and venetoclax plus obinutuzumab prolong progression-free survival (PFS) in patients with chronic lymphocytic leukemia (CLL). Matching-adjusted indirect comparison (MAIC) can be used to compare the efficacy and safety of different treatment regimens when no head-to-head trial has compared the treatments.
Patient matching was conducted using unanchored MAIC propensity-score weighting to compare PFS, overall survival (OS), tolerability, and adverse events (AEs) of interest (AEIs; grade 3-4 infections, neutropenia, febrile neutropenia, and/or thrombocytopenia and AEs leading to treatment discontinuation) on the basis of data from patients in SEQUOIA for zanubrutinib and aggregate data from CLL14 for venetoclax plus obinutuzumab. Because SEQUOIA occurred during the pandemic, analyses were also conducted to adjust for coronavirus disease 2019 (COVID-19) infections.
After matching and adjustment, baseline characteristics of the zanubrutinib group in SEQUOIA were well balanced with the CLL14 population (N = 216), with an effective sample size of 163 for the zanubrutinib group. After matching for baseline characteristics, zanubrutinib demonstrated a robust PFS benefit compared with venetoclax plus obinutuzumab (hazard ratio, 0.66 [95% confidence interval, 0.44-0.97]; P = 0.0351) and higher PFS probability at landmark points (60-month landmarks of 73.9% versus 63%, respectively). OS trended in favor of zanubrutinib. Overall, AEs of any grade over time were comparable in the zanubrutinib safety and venetoclax plus obinutuzumab populations. Zanubrutinib was associated with lower rates of selected AEIs compared with venetoclax plus obinutuzumab at all time points, except for grade 3-4 infections after 156 weeks. After adjusting for COVID-19, zanubrutinib was associated with a significantly lower incidence of grade 3-4 infections at 104 weeks but similar incidences of grade 3-4 infections versus venetoclax plus obinutuzumab during the overall follow-up period.
Continuous treatment with zanubrutinib in treatment-naïve patients with CLL/small lymphocytic lymphoma resulted in prolonged PFS and a favorable safety profile compared with fixed-duration venetoclax plus obinutuzumab.
SEQUOIA (NCT03336333); CLL14 (NCT02242942).
与化疗免疫疗法相比，泽布替尼单药治疗以及维奈克拉联合奥妥珠单抗均可延长慢性淋巴细胞白血病（CLL）患者的无进展生存期（PFS）。当没有头对头试验比较不同治疗方案时，匹配调整间接比较（MAIC）可用于比较不同治疗方案的疗效和安全性。
采用非锚定MAIC倾向评分加权进行患者匹配，以基于泽布替尼的SEQUOIA研究中患者的数据以及维奈克拉联合奥妥珠单抗的CLL14研究汇总数据，比较PFS、总生存期（OS）、耐受性和关注的不良事件（AEIs；3-4级感染、中性粒细胞减少、发热性中性粒细胞减少和/或血小板减少以及导致治疗中断的AE）。由于SEQUOIA研究是在疫情期间进行的，因此还进行了分析以调整2019冠状病毒病（COVID-19）感染情况。
匹配和调整后，SEQUOIA研究中泽布替尼组的基线特征与CLL14研究人群（N = 216）良好平衡，泽布替尼组的有效样本量为163。在匹配基线特征后，与维奈克拉联合奥妥珠单抗相比，泽布替尼显示出显著的PFS获益（风险比，0.66 [95%置信区间，0.44 - 0.97]；P = 0.0351），并且在标志性时间点的PFS概率更高（60个月标志性时间点分别为73.9%和63%）。OS倾向于泽布替尼。总体而言，随着时间推移，泽布替尼组和维奈克拉联合奥妥珠单抗组中任何级别的AE相当。除了156周后3-4级感染外，在所有时间点，泽布替尼组中选定AEIs的发生率均低于维奈克拉联合奥妥珠单抗组。在调整COVID-19因素后，泽布替尼在104周时3-4级感染的发生率显著较低，但在整个随访期间，其3-4级感染的发生率与维奈克拉联合奥妥珠单抗组相似。
在初治的CLL/小淋巴细胞淋巴瘤患者中持续使用泽布替尼治疗，与固定疗程的维奈克拉联合奥妥珠单抗相比，可延长PFS并具有良好的安全性。
SEQUOIA（NCT03336333）；CLL14（NCT02242942）。
