CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Relapsed or Refractory Diffuse Large B-Cell Lymphoma: "Dazed and Confused".
Relapsed or Refractory Diffuse Large B-Cell Lymphoma: "Dazed and Confused".
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
弥漫大 B 细胞淋巴瘤(DLBCL)是最常见的非霍奇金淋巴瘤类型。约 30%–40% 患者会发展为复发/难治性(R/R)DLBCL,导致显著发病率和死亡率。对化疗敏感且适合移植的 R/R DLBCL 患者,标准治疗为挽救性化学免疫治疗,随后进行大剂量化疗和自体干细胞救援(HDT-ASCR)。不适合 HDT-ASCR 或该治疗失败的患者,治疗大多以姑息为目的。
然而,近期CAR-T 细胞疗法及多种获 FDA 批准靶向药物取得进展,正改变 R/R DLBCL 管理格局。目前没有适用于所有患者的单一治疗方案,后续疗法的最佳排序仍未得到满足。本综述重点介绍已获批 CAR-T 构型(包括疗效、不良反应和真实世界数据)、CAR-T 桥接治疗、新兴靶向药物(包括双特异性抗体)的作用,以及靶向药物与 CAR-T 治疗的时序关系。未来前瞻性随机临床试验提供更多证据之前,应根据患者情况个体化治疗,并审慎安排现有药物的使用顺序。
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.
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