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:CAR-FIT: Chimeric Antigen Receptor T-Cell Fitness Index for Therapy-Integrating Comorbidity and Geriatric Assessments to Guide Safe and Equitable Delivery of Chimeric Antigen Receptor T-Cell in Patients with Borderline Physiological Reserve.
患者的体能状态和合并症采用 Eastern Cooperative Oncology Group、Karnofsky、Cumulative Illness Rating Scale(CIRS)、Severe4 和 Cellular Therapy Comorbidity Index(CT-CI)评分进行评估,并分为“fit”、“borderline”或“unfit”。
合适的患者选择对于CAR-T 细胞治疗至关重要,以尽量减少可预防的不良结局并优化资源分配。我们提出一个CAR-T适能指数(CAR-FIT),该指数整合了来自真实世界队列的衰弱和合并症评估,以实现对患者的客观分层。回顾性分析了2020年至2025年间接受CAR-T治疗的80例复发弥漫性大B细胞淋巴瘤患者。结局包括总生存期(OS)、无进展生存期(PFS)和严重治疗相关并发症,定义为3级细胞因子释放综合征、免疫效应细胞相关神经毒性综合征或免疫效应细胞相关血液毒性。使用东部肿瘤协作组、Karnofsky、累积疾病评定量表(CIRS)、Severe4和细胞治疗合并症指数(CT-CI)评分评估患者的适能和合并症,并分类为“适能”、“临界”或“不适能”。使用个体合并症评分,30%(n = 24)有CIRS 7,8.8%(n = 7)有Severe4,5%(n = 4)有CT-CI >3。使用CAR-FIT,患者分为适能(51.2%,n = 41)、临界适能(28.8%,n = 23)和不适能(20%,n = 16)。适能、临界和不适能组之间的1年OS存在显著差异(分别为96.7%,95%置信区间[CI] 90.5至100;66.7%,95% CI 47.3至94.1;45.8%,95% CI 22.2至94.8;P = .03)。1年PFS也观察到相应差异(适能:78.1%,95% CI 65.7至92.9;临界适能:52.9%,95% CI 35.1至79.6;不适能:43.8%,95% CI 22.1至86.8;P < .01)。结合CIRS、Severe4和CT-CI评分与良好的结局分层相关。当与衰弱评估整合时,这种方法可以完善患者选择,以允许更安全地纳入潜在合格候选者。
Appropriate patient selection for chimeric antigen receptor T-cell (CAR-T) therapy is essential to minimize preventable adverse outcomes and optimize resource allocation. We propose a CAR-T fitness index (CAR-FIT) that integrates frailty and comorbidity assessments derived from a real-world cohort to enable objective stratification of patients. Eighty patients with relapsed diffuse large B-cell lymphoma treated with CAR-T therapy between 2020 and 2025 were retrospectively reviewed. Outcomes included overall survival (OS), progression-free survival (PFS), and severe treatment-related complications, defined as grade 3 cytokine release syndrome, immune-effector cell-associated neurotoxicity syndrome, or immune-effector cell-associated hematotoxicity. Patients' fitness and comorbidities were assessed using Eastern Cooperative Oncology Group, Karnofsky, Cumulative Illness Rating Scale (CIRS), Severe4, and Cellular Therapy Comorbidity Index (CT-CI) scores and categorized to either "fit," "borderline," or "unfit." Using individual comorbidities scores, 30% (n = 24) had CIRS 7, 8.8% (n = 7) had Severe4, and 5% (n = 4) had CT-CI >3. With CAR-FIT, patients were fit (51.2%, n = 41), borderline-fit (28.8%, n = 23), and unfit (20%, n = 16). There was a significant difference in 1-yr OS among the fit, borderline and unfit groups (96.7%, 95% confidence interval [CI] 90.5 to 100; 66.7%, 95% CI 47.3 to 94.1; 45.8%, 95% CI 22.2 to 94.8 respectively; P = .03). A corresponding difference in 1-yr PFS was also noted (fit: 78.1%, 95% CI 65.7 to 92.9; borderline-fit: 52.9%, 95% CI 35.1 to 79.6; unfit: 43.8%, 95% CI 22.1 to 86.8; P < .01). Combining CIRS, Severe4, and CT-CI scores correlated with good outcome stratification. When integrated with frailty assessment, this approach can refine patient selection to allow safer access to potentially eligible candidates.
MEMBER ACCOUNT
登录成功会直接打开下一页。