Despite recent advances in frontline therapy for diffuse large B-cell lymphoma (DLBCL), at least a third of those diagnosed still will require second or further lines for relapsed or refractory (rel/ref) disease. A small minority of these can be cured with standard chemoimmunotherapy/stem-cell transplant salvage approaches. CD19-directed chimeric antigen receptor T-cell (CAR-19) therapies are increasingly altering the prognostic landscape for rel/ref patients with DLBCL and related aggressive B-cell non-Hodgkin lymphomas. Long-term follow up data show ongoing disease-free outcomes consistent with cure in 30–40% after CAR-19, including high-risk patients primary refractory to or relapsing within 1 year of frontline treatment. This has made CAR-19 a preferred option for these difficult-to-treat populations. Widespread adoption, however, remains challenged by logistical and patient-related hurdles, including a requirement for certified tertiary care centers concentrated in urban centers, production times of at least 3–4 weeks, and high per-patients costs similar to allogeneic bone-marrow transplantation. Bispecific antibodies (BsAbs) are molecular biotherapies designed to bind and activate effector T-cells and drive them to B-cell antigens, leading to a similar cellular-dependent cytotoxicity as CAR-19. May and June of 2023 saw initial approvals of next-generation BsAbs glofitamab and epcoritamab in DLBCL as third or higher-line therapy, or for patients ineligible for CAR-19. BsAbs have similar spectrum but generally reduced severity of immune related side effects as CAR-19 and can be administered in community settings without need to manufacture patient-specific cellular products. To date and in contrast to CAR-19, however, there is no convincing evidence of cure after BsAbs monotherapy, though follow up is limited. The role of BsAbs in DLBCL treatment is rapidly evolving with trials investigating use in both relapsed and frontline curative-intent combinations. The future of DLBCL treatment is bound increasingly to include effector cell mediated immunotherapies, but further optimization of both cellular and BsAb approaches is needed.

尽管最近在弥漫性大 B 细胞淋巴瘤 (DLBCL) 的一线治疗方面取得了进展，但至少有三分之一的确诊患者仍需要第二线或更多线治疗复发或难治性 (rel/ref) 疾病。其中一小部分可以通过标准化学免疫疗法/干细胞移植挽救方法治愈。 CD19 导向的嵌合抗原受体 T 细胞 (CAR-19) 疗法正在日益改变 rel/ref DLB​​CL 和相关侵袭性 B 细胞非霍奇金淋巴瘤患者的预后情况。长期随访数据显示，CAR-19 治疗后 30-40% 的患者获得了与治愈一致的持续无病结局，其中包括对一线治疗一年内难治或复发的高危患者。这使得 CAR-19 成为这些难治人群的首选。然而，广泛采用仍然面临后勤和患者相关障碍的挑战，包括需要集中在城市中心的经过认证的三级护理中心、至少 3-4 周的生产时间以及类似于同种异体骨髓的每名患者的高成本移植。双特异性抗体 (BsAb) 是一种分子生物疗法，旨在结合和激活效应 T 细胞并将其驱动至 B 细胞抗原，从而产生与 CAR-19 类似的细胞依赖性细胞毒性。 2023 年 5 月和 6 月，下一代 BsAb glofitamab 和 epcoritamab 首次获得批准，作为 DLBCL 的第三线或更高线疗法，或用于不符合 CAR-19 资格的患者。 BsAb 与 CAR-19 具有相似的谱，但通常降低了免疫相关副作用的严重程度，并且可以在社区环境中施用，无需生产患者特异性细胞产品。然而，迄今为止，与 CAR-19 相比，尽管随访有限，但尚无令人信服的 BsAb 单一疗法治愈的证据。双特异性抗体在 DLBCL 治疗中的作用正在迅速发展，多项试验调查了其在复发性和一线治疗意图组合中的应用。 DLBCL 治疗的未来必然越来越多地包括效应细胞介导的免疫疗法，但需要进一步优化细胞和 BsAb 方法。