Fan Fuli, Liu Xiaodan, Su Zhan, Li Saisai, Wang Chuanlei, Wang Shibo, Cui Shuxia, Yan Yuting
Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Hematol Oncol. 2025 Mar;43(2):e70041. doi: 10.1002/hon.70041.
This study compares the safety profiles of two Bruton's tyrosine kinase (BTK) inhibitors, Ibrutinib and Zanubrutinib, in patients with chronic lymphocytic leukemia (CLL). While Ibrutinib has transformed CLL treatment, it is associated with significant adverse events (AEs). Zanubrutinib, a second-generation BTK inhibitor, offers potential for improved safety. In this prospective study, 200 CLL patients were enrolled, with 100 receiving Ibrutinib and 100 receiving Zanubrutinib. Baseline characteristics such as age, sex, body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, and genetic factors were evaluated. AEs and serious AEs (SAEs) were tracked and graded using the Common Terminology Criteria for Adverse Events (CTCAE). Multivariate logistic regression models were conducted to determine predictors of SAE and AEs grade ≥ 3. Adjusted odds ratio (aOR) and 95% confidence interval (CI) were reported. The mean ages of the Ibrutinib and Zanubrutinib groups were 49.65 and 49.16 years, respectively (p = 0.285). The Zanubrutinib group had a higher percentage of patients with worse ECOG status (71% vs. 57%, p = 0.039). Fewer Zanubrutinib patients experienced severe AEs (4% vs. 9%, p = 0.152) or SAEs (8% vs. 17%, p = 0.054). Neutropenia occurred only in the Ibrutinib group (3%). Subgroup analysis showed a higher complication rate with Zanubrutinib in non-refractory patients (11.40% vs. 5.26%, p = 0.065). Stage III CLL was a protective factor of grade ≥ 3 AEs (aOR = 0.007; 95% CI: 0.0003-0.1829) and SAE (aOR = 0.015; 95% CI: 0.001-0.177). While ECOS status (2 vs. 3) resulted in reduced risk of SAE, chromosome 17p deletion emerged as the main risk factor of SAE (aOR = 6.40; 95% CI: 1.33-30.79). Zanubrutinib demonstrated a more favorable safety profile than Ibrutinib, with fewer severe adverse events. It may be a safer alternative for CLL patients, particularly those at higher risk for complications from BTK inhibitors. However, these differences stemmed from variability in baseline clinical characteristics rather than the interventions themselves.
本研究比较了两种布鲁顿酪氨酸激酶（BTK）抑制剂伊布替尼和泽布替尼在慢性淋巴细胞白血病（CLL）患者中的安全性。虽然伊布替尼改变了CLL的治疗方式，但它与显著的不良事件（AE）相关。第二代BTK抑制剂泽布替尼有望提高安全性。在这项前瞻性研究中，招募了200例CLL患者，其中100例接受伊布替尼治疗，100例接受泽布替尼治疗。评估了年龄、性别、体重指数（BMI）、东部肿瘤协作组（ECOG）体能状态和遗传因素等基线特征。使用不良事件通用术语标准（CTCAE）对AE和严重AE（SAE）进行跟踪和分级。进行多变量逻辑回归模型以确定SAE和≥3级AE的预测因素。报告了调整后的优势比（aOR）和95%置信区间（CI）。伊布替尼组和泽布替尼组的平均年龄分别为49.65岁和49.16岁（p = 0.285）。泽布替尼组ECOG状态较差的患者比例更高（71%对57%，p = ）。接受泽布替尼治疗的患者发生严重AE（4%对9%，p = 0.152）或SAE（8%对17%，p = 0.054）的较少。中性粒细胞减少仅发生在伊布替尼组（3%）。亚组分析显示，在非难治性患者中，泽布替尼的并发症发生率更高（11.40%对5.26%，p = 0.065）。III期CLL是≥3级AE（aOR = 0.007；95% CI：0.0003 - 0.1829）和SAE（aOR = 0.015；95% CI：0.001 - 0.177）的保护因素。虽然ECOS状态（2对3）导致SAE风险降低，但17号染色体p缺失是SAE的主要危险因素（aOR = 6.40；95% CI：1.33 - 30.79）。泽布替尼的安全性优于伊布替尼，严重不良事件较少。对于CLL患者，尤其是那些因BTK抑制剂出现并发症风险较高的患者，它可能是一种更安全的选择。然而，这些差异源于基线临床特征的变异性，而非干预措施本身。
