Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore.
Department of Haematology, Tan Tock Seng Hospital, Singapore, Singapore.
Blood Cancer J. 2023 Sep 7;13(1):140. doi: 10.1038/s41408-023-00916-5.
Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. In the absence of randomised trials (RCTs) comparing these regimens, the optimal first-line treatment for WM remains uncertain. In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. We searched key databases from January 2007 to March 2023, including phase II and III trials, including treatment-naïve WM patients treated with rituximab-based regimens or ibrutinib. Response rates, progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. Four phase III and seven phase II trials were included among 736 unique records. Pooled response rates from all comparative and non-comparative trials were 46%, 33% and 26% for bendamustine rituximab (BR), bortezomib-dexamethasone, cyclophosphamide, rituximab (BDRC) and ibrutinib rituximab (IR), respectively. Two-year pooled PFS was 89%, 81% and 82% with BR, BDRC and IR, respectively. Neuropathy was more frequent with bortezomib, while haematologic and cardiac toxicities were more common with chemo-immunotherapy and ibrutinib-based regimens respectively. Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted.
基于利妥昔单抗的化疗免疫治疗目前是瓦尔登斯特伦巨球蛋白血症（WM）的标准一线治疗方法，而伊布替尼已成为一种替代方法。在缺乏比较这些方案的随机试验（RCT）的情况下，WM 的最佳一线治疗仍不确定。在这项系统评价和荟萃分析中，我们旨在评估 WM 一线治疗方案的疗效和安全性。我们从 2007 年 1 月到 2023 年 3 月，检索了关键数据库，包括 II 期和 III 期试验，包括用利妥昔单抗方案或伊布替尼治疗的初治 WM 患者。评估了反应率、无进展生存期（PFS）、总生存期（OS）和毒性。在 736 个独特记录中，纳入了 4 项 III 期和 7 项 II 期试验。所有比较和非比较试验的汇总反应率分别为苯达莫司汀联合利妥昔单抗（BR）为 46%、硼替佐米联合地塞米松、环磷酰胺、利妥昔单抗（BDRC）为 33%、伊布替尼联合利妥昔单抗（IR）为 26%。BR、BDRC 和 IR 的两年 PFS 分别为 89%、81%和 82%。硼替佐米更常引起神经病变，而化疗免疫治疗和伊布替尼为基础的方案更常引起血液学和心脏毒性。我们的研究结果表明，BR 的反应率高于硼替佐米或伊布替尼为基础的联合治疗。需要进行 RCT 比较 BR 与新兴疗法，包括新型布鲁顿酪氨酸激酶抑制剂。
