Clinical efficacy and safety of subcutaneous rituximab in non-Hodgkin lymphoma: a systematic literature review and meta-analysis

The role of subcutaneous (SC) rituximab in the efficacy and safety to non-Hodgkin lymphoma (NHL) is not clear enough. The purpose of this study was to conduct a systematic review and meta-analysis, to assess the efficacy and safety of subcutaneous rituximab to NHL. A full-scale search was carried out based on the set search terms in PubMed, Web of Science, Embase and Cochrane CENTRAL until 12 October 2022 to identify relevant studies of subcutaneous rituximab for NHL. The efficacy and safety outcomes included complete response (CR) plus unconfirmed complete response (CRu), adverse events (AEs), grade ≥3 AEs, serious adverse events (SAEs), administration-related reactions (ARRs), adverse reaction rates. From a total of 758 studies, 9 trials were eligible. The CR/CRu of patients with NHL receiving SC rituximab was 57%, 55% for Diffuse large B-cell lymphoma (DLBCL) and 54% for Follicular lymphoma (FL). The meta-analysis performed on safety demonstrated that AEs of NHL patients with SC rituximab was 85%, grade ≥3 AEs was 38%, SAE was 27% and ARR was 33%. The result also showed that SC rituximab had a high risk of neutropenia and nausea. For NHL patients, there is no significant difference in the efficacy between subcutaneous rituximab and conventional therapy, while subcutaneous injection can shorten exposure time in the hospital and reduce the risk of infection.皮下注射（subcutaneous，SC）利妥昔单抗在非霍奇金淋巴瘤（non-Hodgkin lymphoma，NHL）中的疗效与安全性相关作用尚未完全明确。本研究旨在开展系统评价与Meta分析，评估皮下注射利妥昔单抗用于非霍奇金淋巴瘤的疗效与安全性。研究团队以预设检索式在PubMed、Web of Science、Embase及Cochrane CENTRAL数据库中进行全面检索，检索截止至2022年10月12日，以筛选关于皮下注射利妥昔单抗治疗非霍奇金淋巴瘤的相关研究。本研究的疗效与安全性结局指标包括完全缓解（complete response，CR）伴未确认完全缓解（unconfirmed complete response，CRu）、不良事件（adverse events，AEs）、≥3级不良事件、严重不良事件（serious adverse events，SAEs）、给药相关反应（administration-related reactions，ARRs）及不良反应发生率。最终从758项研究中纳入符合标准的9项临床试验。接受皮下注射利妥昔单抗的非霍奇金淋巴瘤患者总体CR/CRu率为57%，其中弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma，DLBCL）患者为55%，滤泡性淋巴瘤（follicular lymphoma，FL）患者为54%。安全性Meta分析结果显示，接受皮下注射利妥昔单抗的非霍奇金淋巴瘤患者不良事件总发生率为85%，≥3级不良事件发生率为38%，严重不良事件发生率为27%，给药相关反应发生率为33%。本研究同时发现，皮下注射利妥昔单抗存在中性粒细胞减少与恶心的高发生风险。对于非霍奇金淋巴瘤患者而言，皮下注射利妥昔单抗与传统治疗方案的疗效无显著差异，但皮下给药可缩短患者住院暴露时间，降低感染风险。