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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Assessing the role of radiotherapy in patients with refractory or relapsed high-grade B-cell lymphomas treated with CAR T-cell therapy.
Assessing the role of radiotherapy in patients with refractory or relapsed high-grade B-cell lymphomas treated with CAR T-cell therapy.
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估计有30-40%的弥漫性大B细胞淋巴瘤(DLBCL)患者在接受一线化学免疫治疗后会出现复发/难治性疾病。复发/难治性疾病的标准治疗方法是挽救性化疗后行自体干细胞移植,但在现代,这种方法治愈的患者不足20%。这一低治愈率是由于尽管接受了挽救治疗仍为难治性疾病、因医学原因不适合移植或移植后复发所致。CD19靶向嵌合抗原受体(CAR)T细胞疗法已经彻底改变了复发/难治性疾病患者的治疗模式,使缓解率达到52%至93%,一年总生存率在48%至83%之间。
然而,目前从单采到CAR-T 细胞治疗输注的时间需要数周,使许多患者需要桥接治疗来控制疾病进展。放射治疗(RT)已被用作部分患者在CAR-T 输注前的桥接治疗,在化疗难治性疾病中取得了一些显著缓解。
此外,由于免疫调节机制,RT与CAR-T 细胞之间潜在的协同作用引起了相当大的关注,因为根据迄今为止发表的有限病例系列,有人假设RT也可考虑作为CAR-T 失败后的挽救治疗。需要前瞻性试验来验证该模式在CAR-T 细胞治疗后的意义。
An estimated 30-40% of patients with diffuse large B cell lymphoma (DLBCL) will either relapse or have refractory disease with first-line chemoimmunotherapy. The standard approach for relapsed/refractory disease is salvage chemotherapy followed by autologous stem cell transplantation, but this approach cures fewer than 20% of patients in the modern era.
This low cure rate is a result of refractory disease despite salvage therapy, medical ineligibility for transplantation, or relapse following transplantation. CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigm for patients with relapsed or refractory disease, leading to response rates that range between 52% to 93%, and overall survival rates at one year between 48% and 83%.
However, the time from apheresis to infusion of CAR T-cell therapy currently takes several weeks, leaving many patients in need of bridging therapy to control disease progression. Radiation therapy (RT) has been utilized as a bridging therapy prior to CAR T infusion in select patients, with some remarkable responses in chemorefractory disease.
Furthermore, the potential synergy between RT and CAR T-cells due to immunomodulatory mechanisms has generated considerable excitement, as it has been hypothesized that RT could also be considered as a salvage therapy following CAR T failure, based on limited case series published to date. Prospective trials are warranted to validate the significance of this modality following CAR T-cell therapy.
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