Oncology (Williston Park). 2022 Jun 10;36(6):366-375. doi: 10.46883/2022.25920963.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Approximately 30% to 40% of patients will develop relapsed/refractory (R/R) DLBCL, leading to significant morbidity and mortality. Salvage chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell rescue (HDT-ASCR) is the standard of care for chemosensitive and transplant-eligible R/R DLBCL. In patients who are ineligible for HDT-ASCR or who fail HDT-ASCR, treatment is mostly with palliative intent. However, the recent advances with chimeric antigen receptor T-cell (CAR-T) therapy and several FDA-approved targeted agents are changing the current landscape of R/R DLBCL management. There is no one-size-fits-all approach, and guidance regarding optimal sequencing of subsequent therapies is an unmet need. This review highlights the approved CAR-T constructs, including their efficacy, adverse effects, and real-world data; bridging therapy to CAR-T; the role of emerging targeted agents, including bispecific antibodies; and the timing of these targeted agents in relation to CAR-T therapy. Providing individualized treatment with thoughtful sequencing of available agents is essential until future prospective randomized clinical trials provide more insights.
弥漫性大 B 细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤类型。约 30%至 40%的患者会发展为复发/难治性（R/R）DLBCL，导致严重的发病率和死亡率。挽救性化疗免疫治疗后进行高剂量化疗和自体干细胞挽救（HDT-ASCR）是对化疗敏感和适合移植的 R/R DLBCL 的标准治疗方法。对于不适合 HDT-ASCR 或 HDT-ASCR 失败的患者，治疗大多以姑息为目的。然而，嵌合抗原受体 T 细胞（CAR-T）治疗和几种获得 FDA 批准的靶向药物的最新进展正在改变 R/R DLBCL 管理的现有格局。没有一种方法适用于所有患者，关于后续治疗最佳序贯的指导是未满足的需求。本综述重点介绍了已批准的 CAR-T 构建体，包括其疗效、不良反应和真实世界数据；CAR-T 桥接治疗；新兴靶向药物的作用，包括双特异性抗体；以及这些靶向药物与 CAR-T 治疗的时间关系。在未来前瞻性随机临床试验提供更多见解之前，通过深思熟虑地对现有药物进行个体化治疗和精心排序至关重要。
