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:CAR T-cell therapy in aggressive lymphomas-identifying prognostic and predictive markers.
CAR T-cell therapy in aggressive lymphomas-identifying prognostic and predictive markers.
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我们讨论影响复发/难治性大B细胞淋巴瘤患者抗CD19嵌合抗原受体(CAR)T细胞疗效的输注前、输注后及CAR-T 治疗后复发的不同预后因素。尽管抗CD19 CAR-T 总体结果积极,仍有相当比例患者复发。
我们总结了识别应答、持久缓解及生存预测因素的相关工作。输注前,讨论的患者相关因素包括东部肿瘤协作组体能状态评分、年龄和合并症;疾病相关因素包括肿瘤负荷、组织学及生物学特征;此外还考虑炎症相关因素和CAR-T 产品相关因素。CAR-T 输注后,18FDG-PET/CT评估的疾病应答、液体活检监测及CAR-T 扩增等因素对预测生存结局至关重要。18FDG-PET/CT应答评估是确认治疗应答和预测生存的常用检查。液体活检与18FDG-PET/CT联合使用显示出预测结局的潜力。CAR-T 扩增和持续存在对生存的影响不一,部分研究显示其与应答相关。CAR-T 治疗后复发阶段的预后因素包括难治性疾病、复发时间以及CAR-T 输注时乳酸脱氢酶水平升高。鼓励患者参加临床试验对改善结局至关重要。
总体而言,本文全面综述影响复发/难治性大B细胞淋巴瘤患者抗CD19 CAR-T 疗效的预后因素,强调治疗决策需要个体化。
We discuss different pre-infusion, post-infusion and post-CAR T-cell relapse prognostic factors influencing the outcomes of anti-CD19 CAR T-cell therapy in patients with relapsed or refractory large B-cell lymphomas. Despite the overall positive results of anti-CD19 CAR T-cell therapy, a significant percentage of patients relapse.
We summarize the efforts made to identify predictive factors for response and durable remissions and survival. In the pre-infusion setting, the patient-related factors discussed include Eastern Cooperative Oncology Group performance status, age, and comorbidities. Disease-related factors like tumor burden, histology, and biological features are also considered.
In addition, inflammation-related factors and CAR T-cell product-related factors are considered. After CAR T-cell infusion, factors such as disease response assessed by 18FDG-PET/CT scan, liquid biopsy monitoring, and CAR T-cell expansion become crucial in predicting survival outcomes. Response to 18FDG-PET/CT scan is a widely used test for confirming response and predicting survival. Liquid biopsy, in combination with 18FDG-PET/CT scan, has shown potential in predicting outcomes.
CAR T-cell expansion and persistence have shown mixed effects on survival, with some studies indicating their association with response. In the setting of post-CAR T-cell relapse, prognostic factors include refractory disease, time of relapse, and elevated lactate dehydrogenase levels at CAR T-cell infusion. Enrollment in clinical trials is crucial for improving outcomes in these patients.
Overall, we discuss a comprehensive overview of prognostic factors that can influence the outcomes of anti-CD19 CAR T-cell therapy in patients with relapsed or refractory large B-cell lymphomas, highlighting the need for personalized approaches in treatment decision-making.
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