格菲妥单抗在治疗复发难治性弥漫大B细胞 淋巴瘤中的研究进展

Clinical Research Progress on Glofitamab in the Treatment of Relapsed/Refractory Diffuse Large B-Cell lymphoma

摘要: 复发难治性弥漫大B细胞淋巴瘤(Relapsed/Refractory Diffuse Large B-Cell Lymphoma, R/R DLBCL)是一种预后差，治疗手段有限的侵袭性非霍奇金淋巴瘤。目前，除常规化疗与免疫靶向治疗外，以双特异性抗体为代表的新型免疫疗法已成为重要的研究方向，其中格菲妥单抗(Glofitamab)已在我国获批用于治疗R/R DLBCL。该药是一种具有独特2:1结构的CD20/CD3双特异性抗体，可以高亲和力二价稳定结合B淋巴细胞表面的CD20，同时介导CD20⁺ B细胞与CD3⁺ T细胞形成紧密免疫突触，进而激活并重定向T细胞，介导对肿瘤细胞的杀伤。多项国内外临床研究显示，格菲妥单抗单药治疗可在多数患者中诱导深度且持久的缓解，但部分患者仍面临疾病进展；其在联合治疗方案中展现出更优疗效。在安全性方面，主要不良事件如细胞因子释放综合征(Cytokine Release Syndrome, CRS)通过奥妥珠单抗预处理与剂量递增的给药方式已得到有效管理，但感染与血液学毒性仍需密切关注。优化联合治疗策略、探索疗效预测标志物、耐药机制以及最佳治疗线数是未来研究的方向。本文旨在系统综述格菲妥单抗治疗R/R DLBCL的疗效及安全性，以期为临床实践提供参考。

Abstract: Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) is an aggressive non-Hodgkin lymphoma with a poor prognosis and limited therapies. At present, novel bispecific antibodies such as glofitamab, which is approved in China for R/R DLBCL, represent a key therapeutic strategy beyond conventional chemotherapy and immunotherapy. As a CD20/CD3 bispecific antibody with a unique 2:1 structure, it binds to CD20 on B lymphocytes with high affinity, while mediating the formation of tight immune synapses between CD20⁺ B cells and CD3⁺ T cells to activate and redirect T cells for tumor lysis. Clinical studies indicate that single-agent glofitamab induces durable responses in a majority of patients, though some experience disease progression, and it performs better in combination regimens. Regarding safety, cytokine release syndrome (CRS) can be effectively controlled through pretreatment with obinutuzumab and dose escalation; however, attention should be paid to the risks of infections and hematologic toxicities. Future research should focus on optimizing combination approaches, identifying biomarkers of response, exploring resistance mechanisms, and determining optimal treatment sequences. This paper reviews the efficacy and safety of glofitamab in R/R DLBCL for clinical practice.