Department of Medical Oncology, University Hospital Basel and University of Basel, Basel, Switzerland.
Department of Clinical Haematology, Nottingham Hospitals NHS Trust, Nottingham, UK.
Hematol Oncol. 2019 Dec;37(5):548-557. doi: 10.1002/hon.2666. Epub 2019 Oct 9.
The CD-20 antibody rituximab is a standard component of treatment of non-Hodgkin B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). Primary DLBCL of the central nervous system, also called primary central nervous system lymphoma (PCNSL), is a DLBCL confined to the central nervous system. There has been debate whether intravenous rituximab accumulates sufficiently in the central nervous system to exert an effect. In this systematic review, we assess the benefits and harms of rituximab in the treatment of immunocompetent patients with PCNSL. By searching MEDLINE, CENTRAL, and ClincialTrials.gov up to March 2019, we identified randomized controlled trials (RCTs) investigating the effect of rituximab in patients with PCNSL. We extracted study characteristics and results, assessed risk of bias, performed trial-level random-effects meta-analyses, and graded the certainty of evidence. The protocol was registered with PROSPERO (CRD42019121965). Main outcomes were overall survival (time to death), progression-free survival (time to progression or death), quality of life, grades 3 and 4 toxicity, and treatment-related mortality. We included two RCTs with a total of 343 participants. Overall survival was not statistically significantly improved (HR 0.76; 95% CI, 0.52-1.12; low certainty), with 187 fewer to 39 more deaths after 2 years in 1000 treated patients. Low certainty of evidence indicated that rituximab improved progression-free survival (HR 0.65; 95% CI, 0.45-0.95), which translated into 137 fewer progressions or deaths after 2 years in 1000 treated patients (231 to 18 fewer). None of the RCTs provided data on quality of life. We found no evidence that rituximab increased grades 3 and 4 toxicity or treatment-related mortality (RR 0.53; 95% CI, 0.20-1.37; low certainty). Overall, the available evidence suggests with low certainty that rituximab in combination with methotrexate-based chemotherapy may improve progression-free survival in immunocompetent patients with newly diagnosed PCNSL, the pooled effect estimates did not show evidence for improvement of overall survival.
CD-20 抗体利妥昔单抗是治疗非霍奇金 B 细胞淋巴瘤（包括弥漫性大 B 细胞淋巴瘤）的标准组成部分。原发性中枢神经系统弥漫性大 B 细胞淋巴瘤（PCNSL），又称原发性中枢神经系统淋巴瘤，是一种局限于中枢神经系统的弥漫性大 B 细胞淋巴瘤。人们一直在争论静脉注射利妥昔单抗是否能在中枢神经系统中充分积聚以发挥作用。在这项系统评价中，我们评估了利妥昔单抗治疗免疫功能正常的 PCNSL 患者的疗效和安全性。通过检索 MEDLINE、CENTRAL 和 ClincialTrials.gov，我们截至 2019 年 3 月，确定了评估利妥昔单抗对 PCNSL 患者疗效的随机对照试验（RCT）。我们提取了研究特征和结果，评估了偏倚风险，进行了试验水平的随机效应荟萃分析，并对证据质量进行了分级。该方案已在 PROSPERO（CRD42019121965）注册。主要结局是总生存（死亡时间）、无进展生存（进展或死亡时间）、生活质量、3 级和 4 级毒性以及与治疗相关的死亡率。我们纳入了两项共 343 名参与者的 RCT。总生存没有统计学意义上的改善（HR 0.76；95%CI，0.52-1.12；低确定性），在 1000 名治疗患者中，2 年后有 187 例死亡减少到 39 例死亡。低确定性证据表明，利妥昔单抗改善了无进展生存（HR 0.65；95%CI，0.45-0.95），这意味着在 1000 名治疗患者中，2 年后有 137 例进展或死亡减少（231 例减少到 18 例）。没有 RCT 提供生活质量的数据。我们没有发现利妥昔单抗增加 3 级和 4 级毒性或与治疗相关的死亡率的证据（RR 0.53；95%CI，0.20-1.37；低确定性）。总体而言，现有证据表明，在免疫功能正常的新诊断 PCNSL 患者中，利妥昔单抗联合甲氨蝶呤为基础的化疗可能改善无进展生存，但汇总的效果估计并未显示出总体生存改善的证据。
