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:Radiation therapy prior to CAR T-cell therapy in lymphoma: impact on patient outcomes.
Radiation therapy prior to CAR T-cell therapy in lymphoma: impact on patient outcomes.
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我们认为,当前的基础与临床证据支持使用综合性消融桥接放疗(CABI),而非低剂量桥接或挽救性放疗,作为改善 R/R DLBCL 患者 CAR-T 细胞治疗结局的一种有前景的策略。这种潜在获益在肿瘤负荷高和/或病变局限的患者中可能最大,因为这类患者既存在局部复发风险升高,又通常能够安全地接受综合性消融放疗剂量(EQD2 > 39 Gy)治疗。需要开展以假设驱动的临床试验,以前瞻性评估放疗对接受 CAR-T 细胞治疗患者结局的影响。
抗CD19嵌合抗原受体(CAR)T细胞疗法已经彻底改变了难治性或复发性(R/R)弥漫性大B细胞淋巴瘤(DLBCL)患者的治疗模式。尽管如此,大多数患者最终仍会进展。桥接或挽救性放疗(RT)联合CAR-T 细胞疗法已被提出作为改善患者预后的潜在策略,但目前对于哪种方法(如果有的话)有效尚缺乏共识。涵盖领域:我们回顾了耐药性的免疫学和分子机制,以及目前关于接受CAR-T 细胞疗法(联合或不联合桥接或挽救性RT)患者的失败模式、临床危险因素和治疗结局的回顾性数据。
INTRODUCTION: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigm for patients with refractory or recurrent (R/R) diffuse large B-cell lymphomas (DLBCL). Nonetheless, most patients ultimately progress. The use of bridging or salvage radiotherapy (RT) in combination with CAR T-cell therapy has been proposed as potential strategies to improve patient outcomes, but consensus is currently lacking as to which, if either, approach is effective. AREAS COVERED: We reviewed the immunologic and molecular mechanisms of resistance and the current retrospective data on patterns-of-failure, clinical risk factors, and treatment outcomes in patients undergoing CAR T-cell therapy, with and without bridging or salvage RT.
EXPERT OPINION: We believe that current basic and clinical evidence supports the use of comprehensive, ablative bridging irradiation (CABI), as opposed to low-dose bridging or salvage radiotherapy, as a promising strategy to improve CAR T-cell therapy outcomes in patients with R/R DLBCL.
This potential benefit is likely greatest in patients with high tumor burden and/or localized disease, who are both at elevated risk of local recurrence and can often be safely and comprehensively treated with ablative radiation doses (EQD2 > 39 Gy). Hypothesis-driven clinical trials are needed prospectively assess the impact of radiation on outcomes in patients undergoing CAR T-cell therapy.
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