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:Prophylactic Tocilizumab prior to infusion of CD19 CAR T-cells reduces therapy-related complications in older lymphoma patients.
Prophylactic Tocilizumab prior to infusion of CD19 CAR T-cells reduces therapy-related complications in older lymphoma patients.
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尽管真实世界经验已显示各年龄组均可获益,但 70 岁以上患者因细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)等治疗相关并发症需特别关注,这些并发症可能导致不良结局。
CAR(嵌合抗原受体)T细胞疗法已改变了复发/难治性B细胞淋巴瘤(r/r BCL)及浆细胞骨髓瘤的治疗。尽管真实世界经验显示其在各年龄组中均取得成功,但70岁以上患者因细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)等治疗相关并发症而需要特别关注,这些并发症可能导致不良结局。本研究分析了2019年至2023年间接受CAR-T 细胞治疗的26例70岁r/r BCL患者的结局,比较了接受预防性Tocilizumab(N = 7)与标准治疗(N = 19)的患者。中位年龄为75岁,患者既往接受过中位三线治疗。预防性Tocilizumab在CAR-T 细胞回输前1小时给予。接受预防性Tocilizumab的患者治疗相关并发症显著减少(p = 0.039),治疗相关并发症定义为以下事件中的一项或多项:重度CRS、重度ICANS、使用皮质类固醇、需要输血、在重症监护病房治疗、住院时间延长及出院后转入护理机构。Tocilizumab组的总住院时间较短(15.9 vs. 18.5天),但无统计学显著性。两组间的无进展生存期和总生存期相似。结果表明,预防性Tocilizumab可能优化老年CAR-T 细胞患者的管理,与现有关于其在r/r BCL中预防性使用的证据一致。
CAR (chimeric antigen receptor) T-cell therapies have transformed treatment for relapsed and refractory B cell lymphomas (r/r BCL) and plasma cell myeloma. While real-world experiences have shown success across age groups, patients over 70 years require special attention due to therapy-related complications like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which can lead to adverse outcomes. This study analyzed outcomes of 26 r/r BCL patients aged 70 years treated with CAR T-cell therapy between 2019 and 2023, comparing those who received prophylactic Tocilizumab (N = 7) versus standard treatment (N = 19). The median age was 75 years, with patients having received a median of three prior therapy lines. Prophylactic Tocilizumab was given 1 h before re-transfusion of CAR T-cells. Patients receiving prophylactic Tocilizumab experienced significantly fewer therapy-related complications (p = 0.039) which were defined as one or more of the following events: severe CRS, severe ICANS, corticosteroid use, need for transfusions, treatment in a critical care unit, prolonged hospitalization and discharge to a care facility. Hospital stays in total were shorter in the Tocilizumab group (15.9 vs. 18.5 days), though not statistically significant. Progression-free and overall survival were similar between groups. The results suggest that prophylactic Tocilizumab may optimize management of older CAR T-cell patients, aligning with existing evidence regarding its prophylactic use in r/r BCL.
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