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:Impact of neurotoxicity and steroid therapy on cancer progression-free survival in lymphoma patients treated with anti-CD19 CAR T cells.
Impact of neurotoxicity and steroid therapy on cancer progression-free survival in lymphoma patients treated with anti-CD19 CAR T cells.
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我们的研究结果提示,ICANS 和类固醇治疗不会对接受抗 CD19 CAR-T 细胞治疗的淋巴瘤患者的 PFS 产生不良影响。
免疫效应细胞相关神经毒性综合征(ICANS)是嵌合抗原受体(CAR)T细胞治疗的常见并发症。大多数患者症状完全消退且无长期神经系统后遗症,但ICANS及类固醇治疗对肿瘤学结局的影响尚未充分研究。我们研究ICANS和类固醇治疗与无进展生存期(PFS)的关系。
纳入接受抗CD19 CAR-T 细胞治疗的大B细胞淋巴瘤患者。主要结局为90天PFS;次要结局包括第30、90、180和365天的PFS、完全缓解及总生存期(OS)。通过调整基线因素的逻辑回归分析评估结局与ICANS及类固醇治疗的关联。
共纳入241例患者,中位年龄60岁(四分位距[IQR] 51–66岁),女性81例(33.6%),67例(27.8%)发生ICANS,142例(58.9%)达到90天PFS。90天PFS与ICANS发生(调整后比值比[aOR] 1.39;95%置信区间[CI] 0.75–2.61)、最高分级(aOR 1.24;0.97–1.59)、持续时间(每增加1天,aOR 1.00;95% CI 0.95–1.05)或发病时间(每延后1天,aOR 0.98;95% CI 0.86–1.11)均无关联。90天PFS也与类固醇治疗(aOR 1.25;95% CI 0.73–2.14)或累积剂量(每增加100 mg,aOR 1.00;95% CI 0.98–1.01)无关联。次要结局结果相似,但ICANS与30天OS(aOR 0.05;95% CI 0.01–0.54)和90天OS(aOR 0.35;95% CI 0.15–0.80)相关。
研究结果提示,接受抗CD19 CAR-T 细胞治疗的淋巴瘤患者中,ICANS和类固醇治疗不会对PFS产生不利影响;但ICANS可能与早期OS降低相关。
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent complication of chimeric antigen receptor (CAR) T-cell therapy. Most patients achieve complete symptom resolution without long-term neurological sequelae, yet the impact of ICANS and steroid therapy on oncological outcomes remains inadequately explored. We investigated the association between ICANS and steroid therapy with progression-free survival (PFS).
We included large B-cell lymphoma patients treated with anti-CD19 CAR T cells. The primary outcome was 90-day PFS. The secondary outcomes included PFS, complete response, and overall survival (OS) at 30, 90, 180, and 365 days. The association between outcomes and ICANS and steroid treatment was assessed using logistic regression analyses adjusted for baseline factors.
Overall, 241 patients were included. The median age was 60 years (interquartile range [IQR] = 51-66), 81 (33.6%) were females, 67 (27.8%) developed ICANS, and 142 (58.9%) achieved 90-day PFS. There was no association between 90-day PFS and ICANS development (adjusted odds ratio [aOR] 1.39 [95% confidence interval {CI} = 0.75-2.61]), maximum grade (aOR 1.24 [0.97-1.59]), duration (aOR 1.00 [95% CI = 0.95-1.05] per 1-day increase), or day of onset (aOR 0.98 [95% CI = 0.86-1.11] per 1-day increase). There was no association between 90-day PFS and steroid therapy (aOR 1.25 [95% CI = 0.73-2.14]) or cumulative dose (aOR 1.00 [95% CI = 0.98-1.01] per 100-mg increase). Similar results were observed for secondary outcomes, except for an association between ICANS and OS at 30 days (aOR 0.05 [95% CI = 0.01-0.54]) and 90 days (aOR 0.35 [95% CI = 0.15-0.80]).
Our findings suggest that ICANS and steroid therapy do not adversely impact the PFS in lymphoma patients receiving anti-CD19 CAR T cells. Yet, ICANS might be associated with reduced early OS.
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