肿瘤细胞治疗研究
英文原题：CD20 × CD3 Bispecific Antibodies in B-Cell Non-Hodgkin Lymphomas: Current Evidence, Therapeutic Integration, and Future Directions.
背景与目的：尽管化疗免疫治疗和嵌合抗原受体（CAR）T 细胞治疗已取得进展，复发或难治性（R/R）B 细胞非霍奇金淋巴瘤（B-NHL）的结局仍然不佳。
背景与目的：尽管化学免疫治疗和嵌合抗原受体（CAR）T细胞疗法取得进展，复发或难治性（R/R）B细胞非霍奇金淋巴瘤（B-NHL）患者的预后仍然较差。许多患者不适合接受细胞治疗，或在治疗后复发，因此需要有效的现货型免疫治疗。CD20×CD3双特异性抗体（BsAb）可将内源性T细胞重定向至恶性B细胞，已成为B-NHL中有前景的一类疗法。本综述总结mosunetuzumab、glofitamab、epcoritamab和odronextamab治疗B-NHL的现有临床证据，重点关注疗效、安全性和新兴应用。材料与方法：系统梳理评估上述四种目前已获批CD20×CD3 BsAb治疗B-NHL的I–III期临床试验文献，并评估惰性及侵袭性淋巴瘤亚型中的疗效、应答持久性和安全性数据。结果：CD20×CD3 BsAb在既往接受多线治疗的B-NHL患者中显示出显著且持久的临床活性，包括既往接受CAR T细胞治疗的患者。Mosunetuzumab在滤泡性淋巴瘤（FL）中取得较高应答率和持久缓解；glofitamab在侵袭性淋巴瘤，尤其是弥漫性大B细胞淋巴瘤（DLBCL）中显示显著疗效。Epcoritamab在不同淋巴瘤亚型中疗效一致，皮下给药和阶梯递增剂量方案使其耐受性良好。Odronextamab在FL和DLBCL患者中也显示具有临床意义的应答，包括高危人群。各研究中最常见的不良事件为细胞因子释放综合征（CRS），多数为低级别，可采用成熟的减缓措施管理。免疫效应细胞相关神经毒性综合征（ICANS）较少见。感染和血液学毒性，尤其是中性粒细胞减少，是各治疗方案中具有临床意义的不良事件，凸显了加强支持治疗的必要性。结论：CD20×CD3 BsAb是R/R B-NHL治疗的重要进展，兼具较强临床活性、可管理的毒性和现货型可及性。随着其逐步进入更早线治疗并与其他方案联合，预计将进一步改变B-NHL治疗格局。
Background and Objectives : Relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHL) remain associated with poor outcomes despite advances in chemoimmunotherapy and chimeric antigen receptor (CAR) T-cell therapy. Many patients are ineligible for or relapse after cellular therapies, highlighting the need for effective off-the-shelf immunotherapeutic approaches. CD20 CD3 bispecific antibodies (BsAbs) redirect endogenous T cells against malignant B cells and have emerged as a promising therapeutic class in B-NHL. To summarize current clinical evidence regarding mosunetuzumab, glofitamab, epcoritamab, and odronextamab in B-NHL, focusing on efficacy, safety, and emerging therapeutic applications. Materials and Methods : A structured review of published phase I-III clinical trials evaluating the four currently approved CD20 CD3 BsAbs in B-NHL was conducted. Efficacy outcomes, durability of response, and safety data were assessed across indolent and aggressive lymphoma subtypes. Results : CD20 CD3 BsAbs demonstrated substantial and durable clinical activity in heavily pretreated B-NHL, including patients with prior CAR T-cell exposure. Mosunetuzumab showed high response rates and durable remissions in follicular lymphoma (FL), while glofitamab demonstrated significant efficacy in aggressive lymphomas, particularly diffuse large B-cell lymphoma (DLBCL). Epcoritamab exhibited consistent activity across lymphoma subtypes with favorable tolerability supported by subcutaneous administration and step-up dosing. Odronextamab also demonstrated clinically meaningful responses in both FL and DLBCL, including high-risk populations. Across studies, cytokine release syndrome (CRS) was the most common adverse event, predominantly low grade and manageable with established mitigation strategies. Immune effector cell-associated neurotoxicity syndrome (ICANS) was uncommon. Infections and hematologic toxicities, particularly neutropenia, represented clinically relevant adverse events across all treatment programs, highlighting the need for special supportive care. Conclusions : CD20 CD3 BsAbs represent a major therapeutic advancement in R/R B-NHL, combining high clinical activity, manageable toxicity, and off-the-shelf availability. Their expanding integration into earlier treatment settings and combination strategies is expected to further reshape the therapeutic landscape of B-NHL.
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