决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Long-term Therapy Outcomes of CD19/22 CAR T Cell Alone or with Autologous Stem Cell Transplantation for Relapsed/Refractory DLBCL.
该研究纳入 124 例桥接治疗后未获缓解的患者。
研究者对两项单臂试验进行了比较,评估CD19/CD22靶向嵌合抗原受体(CAR19/22)T细胞混合疗法单独使用或联合自体干细胞移植(ASCT)治疗复发/难治性弥漫大B细胞淋巴瘤(R/R DLBCL)的长期疗效和安全性。研究共纳入124例接受桥接治疗后未缓解的患者。主要迟发3级不良事件为血细胞减少(36.92%比52.54%)和感染(29.68%比28.81%)。与单用CAR19/22 T细胞混合疗法相比,联合ASCT的CAR19/22治疗总缓解率更高(最佳总缓解率78.46%比93.22%,P=0.023),无进展生存期更长(中位数5.68个月比未达到,P<0.001),总生存期也更长(中位数27.61个月比未达到,P<0.001)。3个月时达到完全缓解及接受联合治疗是无进展生存和总生存延长的独立预测因素。在倾向评分匹配和逆概率治疗加权等敏感性分析校正后,上述关联仍具有统计学意义。意义:CAR19/22 T细胞疗法联合ASCT可显著提高R/R DLBCL患者的应答率和生存,包括高危患者。该方法似乎改善了疗效与安全性的平衡,为优化CAR-T联合治疗提供了具有临床应用价值的策略。
UNLABELLED: We conducted a comparative analysis of the long-term efficacy and safety of two single-arm trials for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL): CD19/CD22-directed chimeric antigen receptor (CAR19/22) T-cell cocktail therapy alone or combined with autologous stem cell transplantation (ASCT). The study included 124 patients not in remission after bridging therapy. Cytopenia (36.92% vs. 52.54%) and infection (29.68% vs. 28.81%) were the predominant late grade 3 adverse events. CAR19/22 T-cell cocktail therapy combined with ASCT achieved a higher overall response rate (best overall response: 78.46% vs. 93.22%, P = 0.023) and superior progression-free survival (median, 5.68 months vs. not reached, P < 0.001) and overall survival (median, 27.61 months vs. not reached, P < 0.001) than CAR19/22 T-cell cocktail therapy alone. Independent predictors of longer progression-free survival and overall survival included achieving a complete response at 3 months and receiving combination therapy. The associations remained statistically significant after adjustment in sensitivity analyses incorporating propensity score matching and inverse probability of treatment weighting. SIGNIFICANCE: CAR19/22 T-cell therapy combined with ASCT significantly improves response and survival in R/R DLBCL, including high-risk patients. This approach seems to enhance the efficacy-safety balance and offers a clinically actionable strategy to optimize CAR T-cell combination therapies.
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