泽布替尼单药治疗初治和复发/难治性慢性淋巴细胞白血病/小淋巴细胞淋巴瘤：三项研究的汇总分析。
Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies.
机构信息
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
出版信息
Adv Ther. 2022 Sep;39(9):4250-4265. doi: 10.1007/s12325-022-02238-7. Epub 2022 Jul 28.
INTRODUCTION
Zanubrutinib is a highly selective irreversible inhibitor of Bruton tyrosine kinase which has shown significant activity in lymphoid malignancies in early phase studies. We report here the long-term follow-up outcomes of zanubrutinib in various lines of therapy in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
METHODS
This post hoc analysis pooled patients with treatment-naïve (TN) or relapsed/refractory (R/R) CLL/SLL receiving zanubrutinib monotherapy from three phase 1/2 studies (BGB-3111-1002, BGB-3111-AU-003, BGB-3111-205).
RESULTS
A total of 211 patients with CLL/SLL (TN 19, R/R 192) were included. After weighting (TN 19, R/R 24), the overall response rate (ORR) was 95.4% and significantly higher in the TN group than in the R/R group (100 vs. 91.0%, p < 0.0001). ORR was also significantly higher in the TN group than in the one prior line of therapy group (100 vs. 98.9%, p < 0.0001). Among those with R/R disease, the ORR was 97.8% in patients with one prior line of therapy (n = 79) and 90.7% in those with > 1 prior lines of therapy (n = 85; p = 0.080). The median follow-up times were 50.1, 35.7, and 45.9 months for TN, R/R and all cohorts, respectively. Progression-free survival and overall survival were significantly longer in the TN group and only one prior line of therapy group compared with the > 1 prior lines of therapy group (all p < 0.05) and were similar in the TN group compared with the one prior line therapy group. Efficacy was similar regardless of the presence of genomic aberrations. Most frequent grade ≥ 3 adverse events were infections (41.7%), neutropenia (34.1%), and thrombocytopenia (9.4%). Atrial fibrillation occurred in only 1.9% of patients.
CONCLUSIONS
With extended follow-up, zanubrutinib yielded long-term benefits and demonstrated a favorable safety profile for patients with TN or RR CLL/SLL. Earlier utilization of zanubrutinib was associated with better outcomes.
TRIAL REGISTRATION
Clinical Trials.gov identifiers, NCT03189524, NCT02343120 (retrospectively registered), and NCT03206918 (retrospectively registered).
简介
泽布替尼是一种高度选择性的不可逆转的布鲁顿酪氨酸激酶抑制剂，在早期研究中显示出对淋巴恶性肿瘤的显著活性。我们在此报告泽布替尼在慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）患者各种治疗线中的长期随访结果。
方法
本事后分析汇总了来自三项 1/2 期研究（BGB-3111-1002、BGB-3111-AU-003、BGB-3111-205）中接受泽布替尼单药治疗的初治（TN）或复发/难治（R/R）CLL/SLL 患者的数据。
结果
共纳入 211 例 CLL/SLL 患者（TN 19 例，R/R 192 例）。经过加权处理（TN 19 例，R/R 24 例），总体缓解率（ORR）为 95.4%，TN 组明显高于 R/R 组（100%比 91.0%，p<0.0001）。TN 组的 ORR 也明显高于一线治疗组（100%比 98.9%，p<0.0001）。在 R/R 疾病患者中，一线治疗组（n=79）的 ORR 为 97.8%，二线及以上治疗组（n=85）的 ORR 为 90.7%（p=0.080）。TN、R/R 和所有队列的中位随访时间分别为 50.1、35.7 和 45.9 个月。与二线及以上治疗组相比，TN 组和仅一线治疗组的无进展生存期和总生存期明显更长（均 p<0.05），而 TN 组与一线治疗组的无进展生存期和总生存期相似。无论是否存在基因组异常，疗效均相似。最常见的≥3 级不良事件是感染（41.7%）、中性粒细胞减少（34.1%）和血小板减少（9.4%）。房颤仅发生在 1.9%的患者中。
结论
泽布替尼具有长期获益，且安全性良好，可用于治疗初治或复发/难治的 CLL/SLL 患者。早期使用泽布替尼与更好的结果相关。
试验注册
ClinicalTrials.gov 标识符，NCT03189524、NCT02343120（追溯性注册）和 NCT03206918（追溯性注册）。
Zotero 插件