Epworth HealthCare, East Melbourne, VIC 3002, Australia.
Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia.
Int J Mol Sci. 2024 Sep 9;25(17):9736. doi: 10.3390/ijms25179736.
Bispecific antibodies (bsAbs) are an emerging therapy in the treatment of large B-cell lymphomas (LBCLs). There is a gap in the research on the safety and efficacy of bsAbs in adults with LBCL, with current research focusing on the wider non-Hodgkin's lymphoma population. To address this research gap, we conducted a systematic review aiming to evaluate the safety and efficacy outcomes of bsAbs in adults with LBCL. A systematized search was conducted in PubMed, EMBASE, and CENTRAL on 10 April 2024. Interventional clinical trials were eligible for inclusion. Observational studies, reviews, and meta-analyses were excluded. According to the Revised Risk of Bias Assessment Tool for Nonrandomized Studies, the included studies were largely of a high quality for safety outcome reporting, but of mixed quality for efficacy outcome reporting. Due to the heterogeneity of the included studies, the results were discussed as a narrative synthesis. Nineteen early phase studies were evaluated in the final analysis, with a pooled sample size of 1332 patients. Nine bsAbs were investigated across the studies as monotherapy (nine studies) or in combination regimes (10 studies). The rates of cytokine release syndrome were variable, with any grade events ranging from 0 to 72.2%. Infection rates were consistently high across the reporting studies (38-60%). Cytopenias were found to be common, in particular, anemia (4.4-62%), thrombocytopenia (3.3-69%), and neutropenia (4.4-70%). Immune effector cell-associated neurotoxicity syndrome (ICANS) and grade ≥3 adverse events were not commonly reported. Promising efficacy outcomes were reported, with median overall response rates of 95-100% in the front-line and 36-91% in terms of relapsed/refractory disease. The results of this systematic review demonstrate that bsAbs are generally well-tolerated and effective in adults with LBCL. BsAbs appear to have superior tolerability, but inferior efficacy to CAR T-cell therapies in adults with LBCL. Future research on safety and efficacy should focus on evaluating adverse event timing and management, the impact on the patient's quality of life, the burden on the healthcare system, and overall survival outcomes.
双特异性抗体 (bsAbs) 是治疗大 B 细胞淋巴瘤 (LBCL) 的一种新兴疗法。目前，关于 bsAbs 在成人 LBCL 中的安全性和疗效的研究存在空白，当前的研究主要集中在更广泛的非霍奇金淋巴瘤人群上。为了解决这一研究空白，我们进行了一项系统评价，旨在评估 bsAbs 在成人 LBCL 中的安全性和疗效结局。我们于 2024 年 4 月 10 日在 PubMed、EMBASE 和 CENTRAL 进行了系统搜索。纳入符合条件的研究为干预性临床试验。排除观察性研究、综述和荟萃分析。根据非随机研究修订后的偏倚风险评估工具，纳入研究在安全性结局报告方面的质量大多较高，但在疗效结局报告方面的质量参差不齐。由于纳入研究的异质性，结果以叙述性综合形式进行讨论。最终分析评估了 19 项早期阶段研究，纳入了 1332 例患者的汇总样本量。在这些研究中，共研究了 9 种 bsAbs，分别作为单药治疗（9 项研究）或联合治疗方案（10 项研究）。细胞因子释放综合征的发生率各不相同，任何等级的事件发生率为 0 至 72.2%。感染率在整个报告研究中一直较高（38-60%）。发现细胞减少症很常见，尤其是贫血（4.4-62%）、血小板减少症（3.3-69%）和中性粒细胞减少症（4.4-70%）。免疫效应细胞相关神经毒性综合征（ICANS）和≥3 级不良事件并不常见。报告了有前景的疗效结局，一线治疗的中位总缓解率为 95-100%，复发/难治性疾病的缓解率为 36-91%。这项系统评价的结果表明，bsAbs 在成人 LBCL 中通常耐受性良好且有效。bsAbs 在成人 LBCL 中似乎具有更好的耐受性，但疗效低于 CAR T 细胞疗法。未来的安全性和疗效研究应侧重于评估不良事件的发生时间和管理、对患者生活质量的影响、对医疗保健系统的负担以及总体生存结局。
