Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, OH, United States of America.
Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, OH, United States of America; Case Comprehensive Cancer Center, Cleveland, OH, United States of America.
Blood Rev. 2024 Jan;63:101140. doi: 10.1016/j.blre.2023.101140. Epub 2023 Oct 28.
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.
自 2017 年以来，复发或难治性（R/R）弥漫性大 B 细胞淋巴瘤（DLBCL）的可用治疗方法发生了巨大变化。几十年来，基础和转化科学的不断进步导致了免疫肿瘤学的创新。这些创新最终导致在过去 10 年中，美国食品和药物管理局（FDA）批准了 8 种单独的药物用于治疗 R/R DLBCL 患者。对于初始缓解后复发的有移植资格的患者，大剂量化疗和自体造血干细胞移植（HDT-ASCT）仍然是标准治疗方法。对于无移植资格的患者或 HDT-ASCT 后复发的患者，有多种选择。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型作用机制的药物现在可用于 R/R DLBCL 患者。嵌合抗原受体（CAR）T 细胞作为二线治疗方法，用于早期复发的 DLBCL 患者或对初始化疗免疫治疗耐药的患者，其应用越来越多。这些策略的临床获益各不相同，受患者和疾病特征以及所给予的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。尚未确定最佳的药物序贯方案，也没有关于如何最好地安排这些药物的循证共识。这种选择的多样性带来了一个悖论：不断增加的治疗选择最初对患者和提供者是一个福音，但随着选择的进一步增加，它们不再解放。相反，由于缺乏药物之间的直接比较以及最大限度提高患者结果的愿望，更多的选择使 R/R DLBCL 的管理更加具有挑战性。在这里，我们回顾了最近批准的二线和后续线药物，总结了详细说明这些药物使用情况的真实世界数据，并为 R/R DLBCL 中的治疗序贯提供了一个框架。
