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:Impact of poverty and neighborhood opportunity on outcomes for children treated with CD19-directed CAR T-cell therapy.
Impact of poverty and neighborhood opportunity on outcomes for children treated with CD19-directed CAR T-cell therapy.
在206例1至29岁的患者中,35.9%经历家庭贫困,24.9%的社区机会较低。
生活在贫困中的儿童在新诊断的急性淋巴细胞白血病(ALL)中经历过多的复发和死亡。家庭贫困和社区社会决定因素对复发/难治性(r/r)白血病嵌合抗原受体(CAR)T细胞治疗结局的影响描述不足。我们确定了2012年至2020年在CD19靶向CAR T细胞临床试验中接受治疗或接受商业tisagenlecleucel治疗的r/r CD19+ ALL/淋巴母细胞淋巴瘤患者。社会经济地位(SES)在家庭层面进行代理,贫困暴露定义为仅Medicaid保险。低社区机会由Childhood Opportunity Index定义。在206名年龄1至29岁的患者中,35.9%暴露于家庭贫困,24.9%具有低社区机会。未暴露于家庭贫困或低机会社区的患者更可能接受高疾病负荷(>25%)的CAR T细胞治疗,这是一种与较差结局相关的疾病特征,与较不优势患者相比(38% vs 30%;37% vs 26%)。完全缓解(CR)率为93%,按家庭贫困(P = .334)或社区机会(P = .504)无显著差异。在多变量分析中,来自低机会社区的患者与其他患者相比,复发风险增加(P = .006;调整风险比[HR],2.3;95%置信区间[CI],1.3-4.1)。死亡风险无差异(P = .545;调整HR,1.2;95% CI,0.6-2.4)。在成功接受CAR T细胞治疗的儿童中,无论代理SES和社区机会如何,CR和总生存均是公平的。来自更优越家庭和社区的儿童在接受CAR T细胞治疗时疾病负担更高。有必要在临床试验环境之外对多中心结局和可及性差异进行研究。
Children living in poverty experience excessive relapse and death from newly diagnosed acute lymphoblastic leukemia (ALL). The influence of household poverty and neighborhood social determinants on outcomes from chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory (r/r) leukemia is poorly described. We identified patients with r/r CD19+ ALL/lymphoblastic lymphoma treated on CD19-directed CAR T-cell clinical trials or with commercial tisagenlecleucel from 2012 to 2020. Socioeconomic status (SES) was proxied at the household level, with poverty exposure defined as Medicaid-only insurance. Low-neighborhood opportunity was defined by the Childhood Opportunity Index. Among 206 patients aged 1 to 29, 35.9% were exposed to household poverty, and 24.9% had low-neighborhood opportunity. Patients unexposed to household poverty or low-opportunity neighborhoods were more likely to receive CAR T-cell therapy with a high disease burden (>25%), a disease characteristic associated with inferior outcomes, as compared with less advantaged patients (38% vs 30%; 37% vs 26%). Complete remission (CR) rate was 93%, with no significant differences by household poverty (P = .334) or neighborhood opportunity (P = .504). In multivariate analysis, patients from low-opportunity neighborhoods experienced an increased hazard of relapse as compared with others (P = .006; adjusted hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.3-4.1). There was no difference in hazard of death (P = .545; adjusted HR, 1.2; 95% CI, 0.6-2.4). Among children who successfully receive CAR T-cell therapy, CR and overall survival are equitable regardless of proxied SES and neighborhood opportunity. Children from more advantaged households and neighborhoods receive CAR T-cell therapy with a higher disease burden. Investigation of multicenter outcomes and access disparities outside of clinical trial settings is warranted.
MEMBER ACCOUNT
登录成功会直接打开下一页。