Department of Hematology, the First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, China; Key Laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy, Xiamen, China.
Department of Nephrology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Crit Rev Oncol Hematol. 2022 Aug;176:103756. doi: 10.1016/j.critrevonc.2022.103756. Epub 2022 Jul 6.
Secondary central nervous system (CNS) relapses are an uncommon yet devastating complication in diffuse large B cell lymphoma (DLBCL). Although several prophylaxis attempts were employed clinically in order to reduce the CNS relapse rate, the optimal management remained uncertain.
We employed conventional meta-analysis along with Network meta-analysis to investigate an optimal prophylactic strategy. The primary outcome was CNS relapse rate.
A total of thirty-six studies comprising 5 RCTs, one clinical trial and 30 observational studies were included. Rituximab overall was superior in reducing CNS relapse rate, and the statistical significance exists (RR 0.79(0.68-0.93), p = 0.004). In rituximab era, none of intravenous, intrathecal administration or novel target agents could significantly decrease CNS relapse rate in high CNS risk patients. Intensive chemotherapy regimen containing HD-MTX with HD-Ara-C (SUCRA 93.4 %) was ranked as the first in reducing CNS relapse rate followed by no prophylaxis (SUCRA 57.5 %), HD-MTX (SUCRA 53.1 %), IT (SUCRA 34.5 %) and lenalidomide maintenance (SUCRA 11.5 %). In addition, intercalated HD-MTX had a trend of reducing CNS relapse but without statistical significance (RR 0.86(0.44-1.68), p = 0.67). However, i-HD-MTX was associated with increased grade 3-4 toxicities and prolonged inpatient stay. Early HD-MTX exposure also increased the treatment related death.
Our network meta-analysis provides an overview of the relative efficacy of all available CNS prophylaxis strategies in DLBCL. In rituximab era, none of intravenous, intrathecal administration or novel target agents could significantly decrease CNS relapse rate in high CNS risk patients. Further studies with prospective, randomized clinical trials as well as with more focus on novel target agents that could spread blood-brain barriers are suggested.
继发性中枢神经系统（CNS）复发是弥漫性大 B 细胞淋巴瘤（DLBCL）中一种罕见但具有破坏性的并发症。尽管临床上已经尝试了几种预防措施来降低 CNS 复发率，但最佳治疗方法仍不确定。
我们采用常规荟萃分析和网络荟萃分析来研究最佳预防策略。主要结局是 CNS 复发率。
共纳入 36 项研究，包括 5 项 RCT、1 项临床试验和 30 项观察性研究。利妥昔单抗总体上可降低 CNS 复发率，且具有统计学意义（RR 0.79[0.68-0.93]，p=0.004）。在利妥昔单抗时代，静脉、鞘内给药或新型靶向药物均不能显著降低高 CNS 风险患者的 CNS 复发率。含大剂量甲氨蝶呤（HD-MTX）联合大剂量阿糖胞苷（HD-Ara-C）的强化化疗方案（SUCRA 93.4%）在降低 CNS 复发率方面排名第一，其次是无预防措施（SUCRA 57.5%）、HD-MTX（SUCRA 53.1%）、IT（SUCRA 34.5%）和来那度胺维持治疗（SUCRA 11.5%）。此外，间插 HD-MTX 有降低 CNS 复发率的趋势，但无统计学意义（RR 0.86[0.44-1.68]，p=0.67）。然而，i-HD-MTX 与 3-4 级毒性增加和住院时间延长相关。早期 HD-MTX 暴露也增加了治疗相关死亡。
本网络荟萃分析提供了 DLBCL 中所有可用 CNS 预防策略相对疗效的概述。在利妥昔单抗时代，静脉、鞘内给药或新型靶向药物均不能显著降低高 CNS 风险患者的 CNS 复发率。建议开展前瞻性、随机临床试验，并更多地关注可穿透血脑屏障的新型靶向药物。
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