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:Treatment patterns, health care resource utilization, and costs of chimeric antigen receptor T-cell vs standard therapy for relapsed/refractory mantle cell lymphoma in the United States.
Treatment patterns, health care resource utilization, and costs of chimeric antigen receptor T-cell vs standard therapy for relapsed/refractory mantle cell lymphoma in the United States.
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非 CAR-T 与更多使用索引后 LOT 相关,其 TTNT 和无治疗间期也更短。这提示,随着患者循环接受非 CAR-T 治疗,疾病进展更频繁且更早。索引后非 CAR-T vs 索引后 CAR-T 的发作期标准化成本更高。这提示,更早采用 CAR-T 可能减少在越来越昂贵且疗效越来越差的非 CAR-T LOTs 中循环,从而可能降低 R/R MCL 患者的 HRU 和财务负担以及卫生系统的负担。
复发/难治性套细胞淋巴瘤(R/R MCL)的标准治疗(SOC)包括化学免疫治疗和靶向治疗(如布鲁顿酪氨酸激酶抑制剂[BTKis])。2020年新型CAR-T 细胞疗法的获批扩大了治疗选择。
比较接受CAR-T 与非CAR-T SOC(非CAR-T)治疗的R/R MCL传统Medicare和商业保险患者的真实世界患者特征、治疗模式、医疗资源利用(HRU)和费用。
接受过2线及以上治疗(LOTs)并在2016年7月1日至2021年12月31日(Medicare)或2023年6月30日(商业保险)期间持续参加其健康计划的成人R/R MCL患者,根据MCL诊断后研究期间接受的治疗被分为非CAR-T 队列和CAR-T 队列。非CAR-T 队列的索引日期为2L开始时间,CAR-T 队列的索引日期为CAR-T 输注日期。结局包括至下次治疗时间(TTNT)、无治疗间期、MCL相关HRU(住院天数、急诊就诊次数和门诊就诊次数)以及费用(医疗和药房)。
共纳入2,835例非CAR-T 患者和122例CAR-T 患者。与非CAR-T 患者相比,CAR-T 患者更多拥有商业保险(27% vs 17.3%;P < 0.01),更年轻(中位年龄69 vs 74;P < 0.0001),且更多为男性(75.4% vs 64.4%;P = 0.012)。索引后的中位随访时间分别为209.5天(CAR-T)和413天(非CAR-T)。超过三分之一(36.9%)的非CAR-T 患者在索引后接受了3L或更高LOT,中位TTNT随LOT从689天(2L)降至184天(6L)。相比之下,仅15%的CAR-T 患者需要额外LOT,CAR-T 后的中位TTNT未达到。非CAR-T 患者的无治疗间期持续时间同样随LOT下降,而CAR-T 的间期显著长于所有非CAR-T LOT。非CAR-T 中靶向治疗的使用随LOT依次增加(2L:76%;6L:93.2%;BTKi 2L:26.8%;BTKi 6L:34.1%)。CAR-T 后,9%的患者接受了靶向治疗,主要为来那度胺为基础。所有MCL相关的HRU以及医疗和药房费用在CAR-T 后均低于索引后非CAR-T。
Standard of care (SOC) for relapsed/refractory mantle cell lymphoma (R/R MCL) has included chemoimmunotherapy and targeted therapies (eg, Bruton tyrosine kinase inhibitors [BTKis]). The approval of novel chimeric antigen receptor T-cell (CAR T) therapy in 2020 expanded therapeutic options.
To compare real-world patient characteristics, treatment patterns, health care resource utilization (HRU), and costs in traditional Medicare and commercially insured patients with R/R MCL treated with CAR T vs non-CAR T SOC (non-CAR T).
Adult patients with R/R MCL who had received 2 or more lines of therapy (LOTs) and continuously enrolled in their health plan between July 1, 2016, and December 31, 2021 (Medicare), or June 30, 2023 (commercial), were stratified into non-CAR T and CAR T cohorts based on therapy received during the study period after MCL diagnosis. Index date was 2L initiation for the non-CAR T cohort and CAR T infusion date for the CAR T cohort. Outcomes included time to next treatment (TTNT), treatment-free interval, MCL-related HRU (inpatient days, emergency department visits, and outpatient visits), and costs (medical and pharmacy).
2,835 non-CAR T and 122 CAR T patients were included. Compared with non-CAR T patients, CAR T patients were more often commercially insured (27% vs 17.3%; P < 0.01), younger (median age 69 vs 74; P < 0.0001), and male (75.4% vs 64.4%; P = 0.012). Median follow-up after index was 209.5 (CAR T) and 413 (non-CAR T) days. More than one-third (36.9%) of non-CAR T patients received 3L or higher LOT after index and median TTNT decreased with LOT from 689 days (2L) to 184 days (6L). In contrast, only 15% of CAR T patients required additional LOT, and median TTNT post-CAR T was not reached. Duration of treatment-free interval similarly declined with LOT for non-CAR T patients, and the CAR T interval was significantly longer than all non-CAR T LOT. Use of targeted therapies in non-CAR T increased sequentially by LOT (2L: 76%; 6L: 93.2%; BTKi 2L: 26.8%; BTKi 6L: 34.1%). Following CAR T, 9% of patients received targeted therapy, predominantly lenalidomide based. All MCL-related HRU and medical and pharmacy costs were lower post-CAR T than post-index non-CAR T.
Non-CAR T was associated with a greater use of post-index LOT, which also had shorter TTNT and treatment-free intervals. This suggests frequent and earlier progression as patients cycle through non-CAR T therapies. Standardized costs were higher in post-index non-CAR T vs post-CAR T episode periods. This suggests that earlier adoption of CAR T may reduce cycling through increasingly more expensive and less effective non-CAR T LOTs, potentially reducing HRU and financial burdens on patients with R/R MCL and the health system.
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