Massachusetts General Hospital Cancer Center, Boston, MA.
City of Hope National Medical Center, Duarte, CA.
Blood Adv. 2021 Mar 23;5(6):1695-1705. doi: 10.1182/bloodadvances.2020003531.
Chimeric antigen receptor (CAR) T-cell therapies have demonstrated high response rates in patients with relapsed/refractory large B-cell lymphoma (LBCL); however, these therapies are associated with 2 CAR T cell-specific potentially severe adverse events (AEs): cytokine release syndrome (CRS) and neurological events (NEs). This study estimated the management costs associated with CRS/NEs among patients with relapsed/refractory LBCL using data from the pivotal TRANSCEND NHL 001 trial of lisocabtagene maraleucel, an investigational CD19-directed defined composition CAR T-cell product with a 4-1BB costimulation domain administered at equal target doses of CD8+ and CD4+ CAR+ T cells. This retrospective analysis of patients from TRANSCEND with prospectively identified CRS and/or NE episodes examined relevant trial-observed health care resource utilization (HCRU) associated with toxicity management based on the severity of the event from the health care system perspective. Cost estimates for this analysis were taken from publicly available databases and published literature. Of 268 treated patients as of April 2019, 127 (47.4%) experienced all-grade CRS and/or NEs, which were predominantly grade ≤2 (77.2%). Median total AE management costs ranged from $1930 (grade 1 NE) to $177 343 (concurrent grade ≥3 CRS and NE). Key drivers of cost were facility expenses, including intensive care unit and other inpatient hospitalization lengths of stay. HCRU and costs were significantly greater among patients with grade ≥3 AEs (22.8%). Therefore, CAR T-cell therapies with a low incidence of severe CRS/NEs will likely reduce HCRU and costs associated with managing patients receiving CAR T-cell therapy. This clinical trial was registered at www.clinicaltrials.gov as #NCT02631044.
嵌合抗原受体 (CAR) T 细胞疗法在复发/难治性大 B 细胞淋巴瘤 (LBCL) 患者中显示出高缓解率;然而,这些疗法与 2 种 CAR T 细胞特异性的严重不良事件 (AE) 相关:细胞因子释放综合征 (CRS) 和神经事件 (NE)。本研究使用 lisocabtagene maraleucel 的关键 TRANSCEND NHL 001 试验数据,估计了复发/难治性 LBCL 患者 CRS/NE 相关的管理成本。Lisocabtagene maraleucel 是一种研究性 CD19 定向定义组成的 CAR T 细胞产品,具有 4-1BB 共刺激结构域,以相同的 CD8+和 CD4+ CAR+ T 细胞靶剂量给药。本研究对 TRANSCEND 试验中前瞻性确定的 CRS 和/或 NE 发作的患者进行了回顾性分析,根据事件的严重程度从医疗保健系统角度检查了与毒性管理相关的临床试验观察到的医疗资源利用 (HCRU)。本分析的成本估算来自公开数据库和已发表的文献。截至 2019 年 4 月,268 名接受治疗的患者中,127 名 (47.4%) 经历了所有等级的 CRS 和/或 NE,其中大多数为等级≤2 (77.2%)。中位总 AE 管理成本范围为 1930 美元(1 级 NE)至 177343 美元(同时发生≥3 级 CRS 和 NE)。成本的主要驱动因素是设施费用,包括重症监护病房和其他住院患者的住院时间长短。AE 等级≥3 的患者的 HCRU 和成本显著更高 (22.8%)。因此,具有低严重 CRS/NE 发生率的 CAR T 细胞疗法可能会降低与接受 CAR T 细胞治疗的患者管理相关的 HCRU 和成本。这项临床试验在 www.clinicaltrials.gov 上注册为 #NCT02631044。