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等待时间增加对大B细胞淋巴瘤嵌合抗原受体T细胞疗法总体死亡率的影响:离散事件模拟模型

Impact of Increasing Wait Times on Overall Mortality of Chimeric Antigen Receptor T-Cell Therapy in Large B-Cell Lymphoma: A Discrete Event Simulation Model.

作者信息

Tully Stephen, Feng Zeny, Grindrod Kelly, McFarlane Tom, Chan Kelvin K W, Wong William W L

机构信息

University of Waterloo, Kitchener, Ontario, Canada.

University of Guelph, Guelph, Ontario, Canada.

出版信息

JCO Clin Cancer Inform. 2019 Oct;3:1-9. doi: 10.1200/CCI.19.00086.

Abstract

PURPOSE

The development of chimeric antigen receptor (CAR) T cells has transformed oncology treatment, with the potential to cure certain cancers. Although shown to be effective in selected populations and studies, CAR T-cell technology requires considerable health care resources, which may lead to additional wait times to access this type of treatment in future. The objective of our study was to estimate the potential impact of increasing wait times on CAR T-cell therapy effectiveness compared with standard chemotherapy for patients with relapsed/refractory diffuse large B-cell lymphoma.

METHODS

A health system-level discrete event simulation model was developed to project the potential impact of wait times on CAR T-cell therapy for patients with relapsed/refractory diffuse large B-cell lymphoma. Waiting queues and health states related to treatment and clinical progression were implemented. Using data from the literature, we evaluated nine scenarios of using CAR T-cell therapy with wait times ranging from 1 to 9 months. The outcome of interest was 1-year all-cause mortality.

RESULTS

Increasing the wait time of receiving CAR T-cell therapy from 1 to 9 months increased the predicted 1-year mortality rate from 36.1% to 76.3%. Baseline 1-year mortality was 34.0% in patients receiving CAR T-cell therapy with no wait times and 75.1% in patients treated with chemotherapy. This resulted in an increased relative mortality rate of 6.2% to 124.5% over a 1- to 9-month wait time compared with no wait time.

CONCLUSION

We found that modest delays in CAR T-cell therapy significantly hinder its effectiveness. Because CAR T-cell therapy offers a potential cure, it is expected that the uptake rate will be substantially increased once the therapy is regularly funded by a health care system. Wait times may be prolonged if system resource availability does not match the demand. Strategies must be developed to minimize the impact of delays and reduce complications during waiting.

摘要

目的

嵌合抗原受体(CAR)T细胞的发展改变了肿瘤治疗方式,具有治愈某些癌症的潜力。尽管CAR T细胞技术在特定人群和研究中显示出有效性,但它需要大量的医疗资源,这可能导致未来患者获得此类治疗的等待时间增加。我们研究的目的是评估等待时间增加对复发/难治性弥漫性大B细胞淋巴瘤患者CAR T细胞治疗效果的潜在影响,并与标准化疗进行比较。

方法

建立了一个卫生系统层面的离散事件模拟模型,以预测等待时间对复发/难治性弥漫性大B细胞淋巴瘤患者CAR T细胞治疗的潜在影响。实施了与治疗和临床进展相关的等待队列和健康状态。利用文献数据,我们评估了9种使用CAR T细胞治疗的情景,等待时间从1个月到9个月不等。感兴趣的结局是1年全因死亡率。

结果

将接受CAR T细胞治疗的等待时间从1个月增加到9个月,预测的1年死亡率从36.1%提高到76.3%。在无等待时间接受CAR T细胞治疗的患者中,基线1年死亡率为34.0%,接受化疗的患者为75.1%。与无等待时间相比,这导致在1至9个月的等待时间内相对死亡率增加了6.2%至124.5%。

结论

我们发现CAR T细胞治疗的适度延迟会显著阻碍其有效性。由于CAR T细胞治疗提供了治愈的潜力,预计一旦该治疗由卫生保健系统定期资助,其采用率将大幅提高。如果系统资源可用性与需求不匹配,等待时间可能会延长。必须制定策略,以尽量减少延迟的影响并减少等待期间的并发症。

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