Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) worldwide. Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R/R) disease. Recently, the introduction of Pola-R-CHP as front-line therapy has represented a major advance in the management of DLBCL, resulting in improved outcomes. Prognosis of R/R DLBCL patients is poor, particularly for those eligible neither for chimeric antigen receptor (CAR) T-cell therapy nor autologous stem cell transplantation (ASCT), representing a significant unmet clinical need. The advent of bispecific monoclonal antibodies (BsAbs), such as bispecific T-cell engagers (BiTEs), dual affinity retargeting (DART) molecules and IgG-like bispecific antibodies, offers a novel promising therapeutic approach in the treatment of DLBCL, both as frontline treatment and in the R/R setting. BsAbs simultaneously engage two different antigens, a tumor-associated antigen and an immune cell antigen, redirecting T-cells against malignant cells and enhancing the immune response. Most BsAbs developed for the treatment of NHLs engage T-cells via CD3 and malignant B-cells via CD20, a surface antigen expressed on most lymphomatous cells. Engagement of malignant B-cells by BsAbs activates T-cells, leading to the release of multiple cytokines and potentially to two characteristic adverse events: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The most extensively studied BsAbs, in both the frontline and relapsed/refractory (R/R) settings, include epcoritamab, glofitamab, mosunetuzumab, and odronextamab. Epcoritamab and glofitamab have received FDA and EMA approval for R/R DLBCL after two or more systemic line of therapies. EMA has also approved glofitamab in combination with gemcitabine and oxaliplatin (GemOx) for patients with R/R DLBCL ineligible for ASCT, whereas this indication has not been approved by FDA. Odronextamab is approved by EMA for R/R DLBCL and FL in patients who have received at least two prior lines of therapy, but it has not been approved by FDA. Mosunetuzumab is approved by both agencies—but only for R/R follicular lymphoma (FL). BsAbs represent a breakthrough therapy in the treatment of DLBCL, especially in R/R diseases. The purpose of this article is to review the landscape of BsAbs in DLBCL.
弥漫性大B细胞淋巴瘤（DLBCL）是全球最常见的侵袭性非霍奇金淋巴瘤（NHL）。目前，约60%的患者通过一线R-CHOP方案治疗获得治愈，而其余患者则出现原发难治或复发（R/R）疾病。近年来，Pola-R-CHP方案作为一线疗法的引入，标志着DLBCL治疗领域的重大进展，显著改善了患者预后。R/R DLBCL患者的预后较差，尤其对于那些既不符合嵌合抗原受体（CAR）T细胞疗法也不适合自体干细胞移植（ASCT）条件的患者，这构成了临床上亟待满足的重大需求。双特异性单克隆抗体（BsAbs）的出现，如双特异性T细胞衔接器（BiTEs）、双亲和重靶向（DART）分子及IgG样双特异性抗体，为DLBCL的治疗提供了一种前景广阔的新型治疗策略，既可用于一线治疗，也适用于R/R疾病。BsAbs能同时结合两种不同抗原——肿瘤相关抗原和免疫细胞抗原，从而重定向T细胞攻击恶性细胞并增强免疫应答。目前针对NHL开发的大多数BsAbs通过CD3结合T细胞，并通过CD20（一种在大多数淋巴瘤细胞表面表达的抗原）结合恶性B细胞。BsAbs与恶性B细胞的结合会激活T细胞，导致多种细胞因子释放，并可能引发两种特征性不良事件：细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）。在一线及复发/难治性（R/R）治疗领域研究最广泛的BsAbs包括epcoritamab、glofitamab、mosunetuzumab和odronextamab。Epcoritamab与glofitamab已获得美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准，用于接受过两种或以上系统治疗的R/R DLBCL患者。EMA还批准了glofitamab联合吉西他滨与奥沙利铂（GemOx）用于不适合ASCT的R/R DLBCL患者，但FDA尚未批准该适应症。Odronextamab获EMA批准用于至少接受过两种前期治疗的R/R DLBCL和滤泡性淋巴瘤（FL）患者，但尚未获得FDA批准。Mosunetuzumab已获两家监管机构批准，但仅用于R/R滤泡性淋巴瘤（FL）的治疗。BsAbs代表了DLBCL治疗领域的突破性进展，尤其在R/R疾病中。本文旨在系统综述BsAbs在DLBCL治疗中的应用现状。
肿瘤(癌症)患者之家