多发性骨髓瘤 BCMA 嵌合抗原受体 T 细胞分配的伦理挑战:多机构经验。

Ethical Challenges with Multiple Myeloma BCMA Chimeric Antigen Receptor T Cell Slot Allocation: A Multi-Institution Experience.

机构信息

Division of Hematology, Mayo Clinic, Rochester, Minnesota.

Division of Hematology, Mayo Clinic, Rochester, Minnesota.

出版信息

Transplant Cell Ther. 2023 Apr;29(4):255-258. doi: 10.1016/j.jtct.2023.01.012. Epub 2023 Jan 18.

Abstract

Chimeric antigen receptor T cell (CAR-T) therapies are Food and Drug Administration (FDA)-approved for patients with triple refractory multiple myeloma (MM). Real-world access to CAR-T therapy remains challenging owing to supply chain limitations impacting manufacturing. The goal of this study was to evaluate the extent of this issue and how major centers are handling the challenges of CAR-T manufacturing slot allocation. MM CAR-T physician leaders at each CAR-T treatment center across the United States were surveyed. We received responses from 17 of 20 centers. A median of 1 slot is allocated per month per center, and the median number of patients per center on the waitlist since the FDA's approval of idecabtagene vicleucel is 20 (range, 5 to 100). As a result, patients remain on the waitlist for a median of 6 months (range, 2 to 8 months) prior to leukapheresis. For patient selection, all centers reported using a committee of experienced CAR-T physicians to ensure consistency. To ensure transparency, 15 centers make selection criteria, selection timelines, and priority scores readily available for CAR-T providers. Centers also reported using ethical values for selection: (1) equal treatment: time spent on waiting list (n = 12); (2) priority to the worst-off: limited therapeutic options (n = 14), MM burden (n = 11), high Hematopoietic Cell Transplantation Comorbidity Index (n = 5); (3) maximize benefit: most likely to complete apheresis (n = 13) or infusion (n = 13) or to achieve response (n = 8); and (4) social value: younger patients (n = 3). Maximizing benefit was considered the most important criterion by 10 centers. This study is the first attempt to evaluate existing issues with CAR-T access for patients with MM and the variability and challenges in patient selection. Integrating ethical resource allocation strategies, similar to those described here, into formal institutional policies would help streamline access to CAR-T therapy and protect the needs of both current and future patients and physicians.

摘要

嵌合抗原受体 T 细胞(CAR-T)疗法已获得美国食品和药物管理局(FDA)批准,可用于三重难治性多发性骨髓瘤(MM)患者。由于供应链限制影响生产,CAR-T 疗法在实际应用中仍然具有挑战性。本研究旨在评估这一问题的严重程度,以及主要中心如何应对 CAR-T 制造插槽分配的挑战。我们对美国各地每个 CAR-T 治疗中心的 MM CAR-T 医师负责人进行了调查。我们收到了 20 个中心中的 17 个中心的回复。每个中心每月平均分配 1 个插槽,自 idecabtagene vicleucel 获得 FDA 批准以来,每个中心等待名单上的患者中位数为 20 人(范围为 5 至 100 人)。因此,患者在接受白细胞分离术之前,中位等待时间为 6 个月(范围为 2 至 8 个月)。在患者选择方面,所有中心都报告说使用经验丰富的 CAR-T 医师委员会来确保一致性。为了确保透明度,15 个中心使 CAR-T 提供者可以方便地获得选择标准、选择时间表和优先级评分。中心还报告说,他们使用道德价值观进行选择:(1)平等对待:在等待名单上花费的时间(n=12);(2)优先考虑病情最严重的患者:治疗选择有限(n=14)、多发性骨髓瘤负担(n=11)、高造血细胞移植合并症指数(n=5);(3)最大化效益:最有可能完成外周血造血干细胞采集(n=13)或输注(n=13)或达到缓解(n=8);(4)社会价值:年轻患者(n=3)。有 10 个中心认为最大化效益是最重要的标准。本研究首次尝试评估多发性骨髓瘤患者接受 CAR-T 治疗的现有问题,以及患者选择的差异和挑战。将类似本文所述的道德资源分配策略纳入正式机构政策,将有助于简化 CAR-T 治疗的获取,并保护当前和未来患者和医生的需求。

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