Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
Ann Hematol. 2024 Jul;103(7):2231-2244. doi: 10.1007/s00277-023-05486-x. Epub 2023 Oct 16.
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a type of mature B lymphocyte clonal proliferative tumor with a specific immunophenotype. Bruton tyrosine kinase inhibitors (BTKi) have been approved for the treatment of CLL/SLL. However, the efficacy and safety of new-generation BTKi-based regimens have not been systematically studied. In this systematic review, we evaluated the efficacy and safety of new-generation BTKi-based regimens for the treatment of patients with CLL/SLL. A comprehensive search on PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. up to January 31, 2023, was conducted by us. Studies reporting data on CLL/SLL patients treated with new-generation BTKi were included. We assessed the overall response rate (ORR), complete response (CR) rate, and 24-month OS/PFS rates for efficacy analysis. For safety analysis, we evaluated the incidence of grade ≥ 3 adverse events (AEs). The meta-analysis included twenty studies. The pooled ORR for new-generation BTKi was 92% (95% CI, 89-95%, I = 80.68%, P = 0.00), while the pooled CR rate was 10% (95% CI, 6-14%, I = 88.11%, P = 0.00). Research has found that the new-generation BTKi-based therapy had higher efficacy under the following treatment conditions: < 65 years old, treatment-naive (TN)-CLL, and BTKi combination therapy. The ORR/CR rates and 24-month OS/PFS rates of BTKi combination therapy were higher than that of BTKi monotherapy. Compared to acalabrutinib monotherapy, zanubrutinib monotherapy demonstrated higher ORR/CR rates and 24-month OS/PFS rates. Common grade ≥ 3 AEs included cytopenia and hypertension. The new-generation BTKi-based therapy has good tolerance and provides incremental benefits for CLL/SLL patients. Despite the superior efficacy of BTKi combination therapy compared to monotherapy, its AEs rates are relatively high. Compared to acalabrutinib, Zanubrutinib may be the preferred monotherapy for CLL. However, randomized-controlled studies are still needed.
慢性淋巴细胞白血病/小淋巴细胞淋巴瘤 (CLL/SLL) 是一种具有特定免疫表型的成熟 B 淋巴细胞克隆性增殖肿瘤。布鲁顿酪氨酸激酶抑制剂 (BTKi) 已被批准用于治疗 CLL/SLL。然而，新一代 BTKi 为基础的方案的疗效和安全性尚未得到系统研究。在这项系统评价中，我们评估了新一代 BTKi 为基础的方案治疗 CLL/SLL 患者的疗效和安全性。我们全面检索了 PubMed、Embase、Cochrane Library 和 ClinicalTrials.gov，检索时间截至 2023 年 1 月 31 日。纳入报告了接受新一代 BTKi 治疗的 CLL/SLL 患者数据的研究。我们评估了疗效分析中的总缓解率 (ORR)、完全缓解 (CR) 率和 24 个月 OS/PFS 率。对于安全性分析，我们评估了 3 级及以上不良事件 (AE) 的发生率。meta 分析纳入了 20 项研究。新一代 BTKi 的汇总 ORR 为 92%（95% CI，89-95%，I=80.68%，P=0.00），而汇总 CR 率为 10%（95% CI，6-14%，I=88.11%，P=0.00）。研究发现，在以下治疗条件下，新一代 BTKi 为基础的治疗具有更高的疗效：<65 岁、初治（TN）-CLL 和 BTKi 联合治疗。BTKi 联合治疗的 ORR/CR 率和 24 个月 OS/PFS 率高于 BTKi 单药治疗。与阿卡替尼单药治疗相比，泽布替尼单药治疗具有更高的 ORR/CR 率和 24 个月 OS/PFS 率。常见的 3 级及以上 AE 包括血细胞减少症和高血压。新一代 BTKi 为基础的治疗具有良好的耐受性，并为 CLL/SLL 患者带来了额外的获益。尽管 BTKi 联合治疗比单药治疗具有更好的疗效，但 AE 发生率相对较高。与阿卡替尼相比，泽布替尼可能是 CLL 的首选单药治疗方案。然而，仍需要随机对照研究。
