CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Epidemiology and Predictors of 30-Day Readmission in CAR-T Cell Therapy Recipients.
Epidemiology and Predictors of 30-Day Readmission in CAR-T Cell Therapy Recipients.
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使用嵌合抗原受体(CAR)T细胞的新型细胞免疫疗法已改变了多种先前无法治愈的血液系统恶性肿瘤的治疗。自2017年首个CAR-T 细胞产品获美国食品药品监督管理局批准以来,另有五种产品获批用于各种血液系统恶性肿瘤。尽管目前对门诊给药已有更多经验,但CAR-T 治疗最初是在住院环境中进行的。细胞因子释放综合征(CRS)和神经系统副作用(通常称为免疫效应细胞相关神经毒性综合征[ICANS])这些独特并发症,以及较高的感染风险,增加了再入院的风险。鉴于CAR-T 治疗近期才获批,目前缺乏大规模流行病学数据。
本研究旨在描述CAR-T 治疗后住院、再入院的流行病学特征,以及与全因30天再入院相关的因素。这项回顾性队列研究使用2017年至2019年全国再入院数据库来识别因CAR-T 治疗给药而住院的病例。将这些住院病例分类为非霍奇金淋巴瘤、多发性骨髓瘤或白血病后,进行了描述性分析。计算了再入院率,并确定了再入院的病因。使用Cox比例风险模型来阐明与30天再入院相关的因素。
我们还估算了与再入院相关的医疗资源利用情况,包括总住院费用和住院时间。2,964例CAR-T 治疗相关入院中,包括2,176例诊断为非霍奇金淋巴瘤,344例多发性骨髓瘤,以及445例白血病。中位住院时间为15天。大多数CAR-T 治疗接受者为男性(63.4%),入住教学医院(99.2%);49.3%拥有私人保险,33.2%属于最高收入社区。CAR-T 治疗主要在私立(89.5%)大型医院(74.4%)、位于大都市地区(91.4%)实施。中位总住院费用以非霍奇金淋巴瘤最高,其次为白血病和多发性骨髓瘤($945,645 vs $265,034 vs $184,194;P < .001)。索引住院期间全因死亡率以白血病最高,为8.6%,其次为非霍奇金淋巴瘤3.6%和多发性骨髓瘤1.4%(P < .001)。
30天全因再入院率为23.6%,中位再入院时间为7天。再入院率以白血病最高,其次为非霍奇金淋巴瘤和多发性骨髓瘤(34.2% vs 22.8% vs 15.7%;P < .001)。再入院产生额外中位总住院费用$64,561。再入院期间,中位住院时间为5天,院内死亡率为4.9%。再入院的主要病因依次为癌症或治疗相关(22%)、脓毒症或感染(18%)、神经系统事件(15%)、中性粒细胞减少或全血细胞减少(11%),以及发热、低血压或缺氧(8%)。在多变量分析中,非霍奇金淋巴瘤和白血病(与多发性骨髓瘤相比)、出院时转至机构、慢性肾脏病、脑血管疾病和无创通气与再入院 odds 较高相关。相反,入住教学医院预示再入院 odds 较低。近四分之一的CAR-T 治疗接受者在最初30天内再入院,导致额外经济负担和大量医疗资源利用。
The novel cellular immunotherapy using chimeric antigen receptor (CAR) T cells has transformed the management of several previously incurable hematologic malignancies. Since the first CAR-T cell product was approved by the Food and Drug Administration in 2017, five additional products have been approved for various hematologic malignancies. Although there is now more experience with outpatient administration, CAR-T therapy was initially delivered in an inpatient setting. The unique complications of cytokine release syndrome (CRS) and neurologic side effects (commonly known as immune effector cell-associated neurotoxicity syndrome [ICANS]), along with a higher risk for infection, increase the risk for hospital readmission.
Given the recent approval of CAR-T therapy, large-scale epidemiologic data are lacking. The present study aimed to characterize the epidemiology of hospitalizations, readmissions, and factors associated with all-cause 30-day readmission post CAR-T therapy. This retrospective cohort study used the Nationwide Readmissions Database from 2017 to 2019 to identify hospitalizations for CAR-T therapy administration.
A descriptive analysis was performed after categorizing these hospitalizations as non-Hodgkin lymphoma, multiple myeloma, or leukemia. The readmission rate was calculated, and etiologies of readmission were identified. A Cox proportional hazards model was used to elucidate factors associated with 30-day readmission.
We also estimated the healthcare utilization related to readmissions, including total hospital charges and length of stay. The 2,964 CAR-T therapy-related admissions included 2,176 with a diagnosis of non-Hodgkin lymphoma, 344 with multiple myeloma, and 445 with leukemia. The median length of stay was 15 days. Most CAR-T therapy recipients were male (63. 4%), admitted to a teaching hospital (99. 2%); 49. 3% had private insurance, and 33. 2% belonged to the highest-income communities. CAR-T therapy was administered mostly in privately owned (89. 5%) large-sized hospitals (74. 4%) in large metropolitan regions (91. 4%). Median total hospital charges were highest for non-Hodgkin lymphoma, followed by leukemia and multiple myeloma ($945,645 versus $265,034 versus $184,194; P < . 001). All-cause mortality during index hospitalization was highest for leukemia at 8. 6%, followed by 3. 6% for non-Hodgkin lymphoma and 1. 4% for multiple myeloma (P < . 001). The 30-day all-cause readmission rate was 23. 6%, and the median time to readmission was 7 days.
The readmission rate was highest for leukemia, followed by non-Hodgkin lymphoma and multiple myeloma (34. 2% versus 22. 8% versus 15. 7%; P < . 001). Readmission incurred an additional median total hospital charge of $64,561. During readmission, median length of stay was 5 days, and in-hospital mortality was 4. 9%. Top etiologies for readmission were cancer or treatment-related (22%), sepsis or infection (18%), neurologic events (15%), neutropenia or pancytopenia (11%), and fever, hypotension, or hypoxia (8%).
On multivariable analysis, non-Hodgkin lymphoma and leukemia (compared with multiple myeloma), transfer to a facility at discharge, chronic renal disease, cerebrovascular disease, and noninvasive ventilation were associated with higher odds of readmission. In contrast, admission to a teaching hospital predicted lower odds of readmission. Almost a quarter of CAR-T therapy recipients are readmitted within the first 30 days resulting in additional economic burden and substantial healthcare utilization.
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