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
预测接受 IL-6 敲低抗 CD19 CAR-T 细胞治疗的复发/难治性 B 细胞急性淋巴细胞白血病患者发生细胞因子释放综合征的风险因素探究
英文原题：Investigation of the risk factors to predict cytokine release syndrome in relapsed or refractory B-cell acute lymphoblastic leukemia patients receiving IL-6 knocking down anti-CD19 chimeric antigen receptor T-cell therapy.
查看英文原题
Investigation of the risk factors to predict cytokine release syndrome in relapsed or refractory B-cell acute lymphoblastic leukemia patients receiving IL-6 knocking down anti-CD19 chimeric antigen receptor T-cell therapy.
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。
中文摘要
CD19 嵌合抗原受体-T（CAR-T）细胞疗法在复发/难治性 B 细胞急性淋巴细胞白血病（r/r B-ALL）患者中取得了显著疗效。
然而，细胞因子释放综合征（CRS）作为常见毒性出现在大多数患者中，而以白细胞介素-6（IL-6）急剧升高为特征的严重 CRS（sCRS）可能危及生命。
我们开展了一项 ssCAR-T-19 细胞的 II 期临床试验，该细胞为携带靶向 IL-6 的 shRNA 的抗 CD19 CAR-T 细胞，共纳入 61 例 r/r B-ALL 患者。该试验注册于 www.ClinicalTrials.gov，注册号为 #NCT03275493。52 例患者达到 CR，9 例被认为 NR。中位缓解持续时间（DOR）和总生存期（OS）均未达到（>50 个月）。81.97% 的患者发生 CRS，其中 54.10% 为 1 至 2 级（1 级，31.15%；2 级，22.95%），27.87% 为 3 至 4 级（3 级，26.23%；4 级，1.64%）。sCRS 的发生早于轻度 CRS（mCRS）。对基线特征的多因素分析确定，输注前高骨髓疾病负荷和不良遗传学风险是 sCRS 的独立危险因素。输注后，与 mCRS 患者相比，sCRS 患者表现出 ssCAR-T-19 细胞更大程度的扩增、更高的 IL-6、IL-10 和 IFN- 峰值水平，并遭受更严重的血液学和非血液学毒性。
展开英文摘要原文
CD19 chimeric antigen receptor-T (CAR-T) cell therapy has achieved remarkable results in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).
However, the cytokine release syndrome (CRS) was presented in most patients as common toxicity and severe CRS (sCRS) characterized by the sharp increase in interleukin-6 (IL-6) could be life-threatening.
We conducted a phase II clinical trial of ssCAR-T-19 cells, anti-CD19 CAR-T cells with shRNA targeting IL-6, in 61 patients with r/r B-ALL. This trial was registered at www. clinicaltrials. gov as #NCT03275493. Fifty-two patients achieved CR while nine patients were considered NR. The median duration of response (DOR) and overall survival (OS) were not reached (>50 months). CRS developed in 81. 97% of patients, including 54. 10% with grades 1 to 2 (grade 1, 31. 15%; grade 2, 22. 95%) and 27.
87% with grades 3 to 4 (grade 3, 26. 23%; grade 4, 1. 64%). sCRS occurs earlier than mild CRS (mCRS). A multivariable analysis of baseline characteristics identified high bone marrow disease burden and poor genetic risk before infusion as independent risk factors for sCRS. After infusion, patients with sCRS exhibited larger expansion of ssCAR-T-19 cells, higher peak levels of IL-6, IL-10, and IFN- , and suffered more severe hematological and non-hematological toxicities compared with those with mCRS.
论文信息
- 作者
- Gong WJ、Qiu Y、Li MH、Chen LY、Li YY、Yu JQ、Kang LQ、Sun AN
- 单位
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.China
- 文献类型
- II 期临床试验
- 期刊
- Frontiers in immunology2022
- 原文标识
- PubMed 36105799 · DOI 10.3389/fimmu.2022.922212
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →