自 2017 年以来，复发或难治性 (R/R) 弥漫性大 B 细胞淋巴瘤 (DLBCL) 的可用治疗方法经历了巨大的变化。几十年来基础科学和转化科学的不断进步带来了免疫肿瘤学的创新。这些创新最终导致美国食品和药物管理局在过去 10 年中分别批准了八项用于治疗 R/R DLBCL 患者的药物。高剂量治疗和自体干细胞移植（HDT-ASCT）仍然是初次缓解后复发的符合移植资格的患者的标准治疗方法。对于不适合移植的患者或 HDT-ASCT 后复发的患者，存在多种选择。针对 CD19 的单克隆抗体、抗体药物偶联物、双特异性抗体、免疫效应细胞产品和其他具有新颖作用机制的药物现在可用于 R/R DLBCL 患者。越来越多地使用嵌合抗原受体 (CAR) T 细胞作为 DLBCL 早期复发患者或初始化学免疫治疗难治患者的二线治疗。这些策略的临床益处各不相同，并受到患者和疾病特征以及先前治疗类型的影响。因此，临床医生在治疗 R/R DLBCL 时可能会遇到多种临床情况。最佳药物顺序尚未确定，并且对于如何最好地订购这些药物也没有基于证据的共识。如此丰富的选择引入了一个悖论：治疗选择的增多最初对患者和提供者来说是一种福音，但随着选择的进一步增加，它们不再具有解放性。相反，由于缺乏药物之间的直接比较以及最大化患者治疗效果的愿望，更多的选择使 R/R DLBCL 的治疗更具挑战性。在这里，我们对最近批准的二线和后续药物进行了回顾，总结了详细说明这些药物使用的真实世界数据，并提供了 R/R DLBCL 测序治疗的框架。版权所有 © 2023。由 Elsevier 出版有限公司

The available treatments for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have experienced a dramatic change since 2017. Incremental advances in basic and translational science over several decades have led to innovations in immune-oncology. These innovations have culminated in eight separate approvals by the US Food and Drug Administration for the treatment of patients with R/R DLBCL over the last 10 years. High-dose therapy and autologous stem cell transplant (HDT-ASCT) remains the standard of care for transplant-eligible patients who relapse after an initial remission. For transplant-ineligible patients or for those who relapse following HDT-ASCT, multiple options exist. Monoclonal antibodies targeting CD19, antibody-drug conjugates, bispecific antibodies, immune effector cell products, and other agents with novel mechanisms of action are now available for patients with R/R DLBCL. There is increasing use of chimeric antigen receptor (CAR) T-cells as second-line therapy for patients with early relapse of DLBCL or those who are refractory to initial chemoimmunotherapy. The clinical benefits of these strategies vary and are influenced by patient and disease characteristics, as well as the type of prior therapy administered. Therefore, there are multiple clinical scenarios that clinicians might encounter when treating R/R DLBCL. An optimal sequence of drugs has not been established, and there is no evidence-based consensus on how to best order these agents. This abundance of choices introduces a paradox: proliferating treatment options are initially a boon to patients and providers, but as choices grow further they no longer liberate. Rather, more choices make the management of R/R DLBCL more challenging due to lack of direct comparisons among agents and a desire to maximize patient outcomes. Here, we provide a review of recently-approved second- and subsequent-line agents, summarize real-world data detailing the use of these medicines, and provide a framework for sequencing therapy in R/R DLBCL.Copyright © 2023. Published by Elsevier Ltd.