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:Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience.
Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience.
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市售抗 CD19 嵌合抗原受体(CAR)T 细胞已为持续扩大的人群带来长期生存机会。鉴于治疗会引发新型毒性,包括细胞因子释放综合征(CRS)和神经毒性(ICANS),本研究在真实世界环境中记录该治疗的安全性和毒性。研究纳入 31 例转诊至本中心接受 CAR-T 治疗的成年患者,其中 12 例输注 tisagenlecleucel,14 例输注 axicabtagene ciloleucel,5 例输注 brexucabtagene autoleucel。26 例出现 CRS,7 例出现神经毒性。18 例 CRS 患者接受 tocilizumab 治疗;另有 1 例患者发生 III 级 CRS,继而出现 I 级 ICANS,接受短期低剂量类固醇治疗。仅 2 例套细胞淋巴瘤(MCL)患者接受高剂量类固醇、anakinra 和 siltuximab 治疗。中位随访 13.4 个月时,9 例患者达到完全缓解(CR)。1 年无进展生存率(PFS)和总生存率(OS)分别为 41.2% 和 88.1%。MCL 诊断(其与使用 brexucabtagene autoleucel 重合)是唯一与较差 OS 独立相关的因素(p < 0.001);乳酸脱氢酶(LDH)升高可独立预测 PFS(p = 0.027)。
此外,第 14 天 C 反应蛋白(CRP)与较差 OS 相关(p = 0.001)。因此,我们的真实世界经验证实,市售 CAR-T 疗法可以在毒性较轻的情况下实施。
Commercially available anti-CD19 chimeric antigen receptor T cells (CAR cells) have offered long-term survival to a constantly expanding patient population. Given that novel toxicities including cytokine release syndrome (CRS) and neurotoxicity (ICANS) have been observed, we aimed to document the safety and toxicity of this treatment in a real-world study.
We enrolled 31 adult patients referred to our center for CAR T therapy. Tisagenlecleucel was infused in 12 patients, axicabtagene ciloleucel in 14, and brexucabtagene autoleucel in 5. Cytokine release syndrome was noted in 26 patients while neurotoxicity was observed in 7. Tocilizumab was administered for CRS in 18 patients, along with short-term, low-dose steroid administration in one patient who developed grade III CRS and, subsequently, grade I ICANS.
High-dose steroids, along with anakinra and siltuximab, were administered in only two MCL patients. With a median follow-up time of 13. 4 months, nine patients were then in CR. The progression-free (PFS) and overall survival (OS) rates were 41. 2% and 88. 1% at one year, respectively. MCL diagnosis, which coincides with the administration of brexucabtagene autoleucel, was the only factor to be independently associated with poor OS ( p < 0. 001); meanwhile, increased LDH independently predicted PFS ( p = 0. 027).
In addition, CRP at day 14 was associated with a poor OS ( p = 0. 001).
Therefore, our real-world experience confirmed that commercial CAR T therapy can be administered with minimal toxicity.
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