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:Two decades of progress, persistent inequity: national trends in multiple myeloma mortality in the United States, 1999-2024.
美国MM死亡率在过去25年中大幅下降,2012年后改善加速,这与新型疗法的影响一致。然而,按种族、性别、年龄、地理和城乡划分的重大不平等仍然存在,并预计将持续至2034年。缩小这些差异不仅需要持续的治疗进展,还需要公平的医疗可及性、更早的诊断,以及改善服务不足人群在临床研究中的代表性。
尽管多发性骨髓瘤(MM)治疗取得了重大进展,包括蛋白酶体抑制剂、免疫调节剂、抗CD38单克隆抗体和CAR-T 细胞疗法,但这些创新在多大程度上转化为美国人口和地理亚组中公平的人群水平死亡率下降仍不清楚。我们评估了1999-2024年全国MM死亡率趋势,并预测了至2034年的轨迹,按性别、年龄、种族/族裔、人口普查区域、城市化程度和死亡地点进行分层。
MM相关死亡病例通过CDC Wide-Ranging Online Data for Epidemiologic Research(CDC WONDER)数据库,使用ICD-10代码C90.0,从1999-2024年识别。每1,000,000人口的年龄调整死亡率(AAMRs)使用2000年美国标准人口计算。时间趋势使用joinpoint回归(Joinpoint Regression Program v6.0.1,National Cancer Institute)评估,生成年度百分比变化(APCs)和平均年度百分比变化(AAPCs)。统计学显著性定义为p<0.05。使用由Akaike信息准则选择的Autoregressive Integrated Moving Average(ARIMA)模型,预测至2034年全国和亚组特异性AAMRs,并给出95%置信区间。
1999-2024年间,MM相关总体AAMR从每1,000,000人口37.6降至25.1(AAPC -1.8%;95% CI -2.1至-1.5;p<0.001)。2012年后死亡率下降显著加速(APC -3.2%;p<0.001),与新型治疗药物的广泛采用相吻合。男性AAMR始终高于女性(2024年为每1,000,000人口32.4 vs 19.8)。Black或African American个体在整个研究期间承受最高的死亡负担,2024年AAMR超过White个体的两倍(每1,000,000人口48.0 vs 23.5)。年龄≥65岁的成年人死亡负担最高(2024年为每1,000,000人口175,较1999年的230下降)。South和非大都市地区死亡率始终高于其他地区和大都市地区。ARIMA预测估计到2034年全国死亡率将持续下降至约每1,000,000人口20.0(95% CI 17.5-22.5),但种族、地理和社会人口学差异预计将持续存在。
BACKGROUND: Despite major advances in multiple myeloma (MM) therapy including proteasome inhibitors, immunomodulatory agents, anti-CD38 monoclonal antibodies, and chimeric antigen receptor T-cell therapies the extent to which these innovations have translated into equitable population-level mortality reductions across U.S. demographic and geographic subgroups remains unclear. We evaluated national MM mortality trends from 1999-2024 and projected trajectories through 2034, stratified by sex, age, race/ethnicity, census region, urbanization, and place of death. METHODS: MM-related deaths were identified from the CDC Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database using ICD-10 code C90.0 from 1999-2024. Age-adjusted mortality rates (AAMRs) per 1,000,000 population were calculated using the 2000 U.S. standard population. Temporal trends were assessed using joinpoint regression (Joinpoint Regression Program v6.0.1, National Cancer Institute), generating annual percent changes (APCs) and average annual percent changes (AAPCs). Statistical significance was defined as p<0.05. Autoregressive Integrated Moving Average (ARIMA) models selected by Akaike Information Criterion were used to project national and subgroup-specific AAMRs through 2034 with 95% confidence intervals. RESULTS: From 1999-2024, overall MM-related AAMRs declined from 37.6 to 25.1 per 1,000,000 population (AAPC -1.8%; 95% CI -2.1 to -1.5; p<0.001). Mortality decline accelerated significantly after 2012 (APC -3.2%; p<0.001), coinciding with widespread adoption of newer therapeutic agents. Males consistently demonstrated higher AAMRs than females (32.4 vs 19.8 per 1,000,000 in 2024). Black or African American individuals experienced the highest mortality burden throughout the study period, with 2024 AAMRs more than double those of White individuals (48.0 vs 23.5 per 1,000,000). Adults aged ≥65 years had the highest mortality burden (175 per 1,000,000 in 2024, down from 230 in 1999). The South and nonmetropolitan regions consistently showed higher mortality rates than other regions and metropolitan areas. ARIMA projections estimate continued national decline to approximately 20.0 per 1,000,000 (95% CI 17.5-22.5) by 2034, although racial, geographic, and sociodemographic disparities are projected to persist. CONCLUSIONS: MM mortality in the United States has declined substantially over the past 25 years, with accelerated improvement after 2012 consistent with the impact of novel therapies. However, major inequities by race, sex, age, geography, and rurality remain and are projected to persist through 2034. Reducing these disparities will require not only continued therapeutic advances but also equitable access to care, earlier diagnosis, and improved representation of underserved populations in clinical research.
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