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:Chimeric antigen receptor T-cell therapy yields similar outcomes in patients with and without cytokine release syndrome.
Chimeric antigen receptor T-cell therapy yields similar outcomes in patients with and without cytokine release syndrome.
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嵌合抗原受体(CAR)T细胞疗法已经彻底改变了许多侵袭性复发/难治性大B细胞淋巴瘤(LBCL)患者的治疗。治疗可能因临床上明显的细胞因子释放综合征(CRS)而复杂化,CRS以发热、低氧血症和低血压为特征,并可能危及生命。大多数接受CAR-T 细胞治疗的患者会发生CRS,这被认为是一种免疫现象。此前尚不清楚未发生CRS的患者是否CAR-T 细胞活性降低,因此可能预后更差。
我们对美国8个学术医学中心接受axicabtagene ciloleucel或tisagenlecleucel治疗LBCL的352例成年患者进行了多中心回顾性分析。关注的结局包括无进展生存期、总生存期、完全缓解率和总缓解率。在纳入的患者中,262例(74.4%)发生了CRS。发生CRS的患者与未发生CRS的患者在无进展生存期(P = .99)或总生存期(P = .16)方面无显著差异。在多变量分析中,治疗期间峰值铁蛋白水平>5000 ng/mL以及淋巴细胞清除化疗前乳酸脱氢酶水平高于机构正常上限与显著更差的无进展生存期和总生存期相关。发生CRS与未发生CRS的患者在完全缓解率或总缓解率方面无显著差异。在这项回顾性分析中,我们报告,接受商业化抗CD19 CAR-T 细胞治疗的患者中,发生CRS的患者临床结局与未发生CRS的患者相似。
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of many patients with aggressive relapsed or refractory large B-cell lymphoma (LBCL). Treatment can be complicated by clinically evident cytokine release syndrome (CRS), which is characterized by the development of fever, hypoxia, and hypotension, and can be life-threatening.
Most patients treated with CAR-T cells develop CRS, which is thought to represent an immune phenomenon. It was previously unknown whether patients who did not develop CRS had reduced CAR-T cell activity and were therefore likely to have worse outcomes.
We conducted a multicenter retrospective analysis of 352 adult patients treated at 8 academic medical centers in the United States who received axicabtagene ciloleucel or tisagenlecleucel for the treatment of LBCL. The outcomes of interest included progression-free survival, overall survival, complete response rate, and overall response rate. Of the included patients, 262 (74. 4%) developed CRS. There was no significant difference in progression-free survival (P = . 99) or overall survival (P = . 16) between patients who developed CRS and those who did not develop CRS.
Peak ferritin levels >5000 ng/mL during treatment and lactate dehydrogenase levels greater than the institutional upper limit of normal before lymphodepleting chemotherapy were associated with significantly worse progression-free and overall survival in the multivariate analysis.
There was no significant difference in the complete response or overall response rates between patients who did and did not develop CRS. In this retrospective analysis, we report that patients who develop CRS have clinical outcomes similar to those of patients without CRS treated with commercial anti-CD19 CAR-T cells.
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