这篇综述的目的是确定嵌合抗原受体T细胞(CAR-T)疗法的成本效益分析中的变异性来源,tisagenlecleucel和axicabtageneciloleucel,由卫生技术评估(HTA)机构评估,与老年患者相比,关注年轻人。
来自澳大利亚的儿童急性淋巴细胞白血病(ALL)和成人弥漫性大B细胞淋巴瘤(DLBCL)的HTA评估。加拿大,英格兰,挪威,和美国。关键临床证据,经济方法,和结果(成本,质量调整寿命年[QALYs]和增量成本效益比)进行了总结。
确定了14项HTA评估(所有5项,9DLBCL[4tisagenlecleucel,5axicabtagene])。分析是CAR-Ts的前瞻性单臂研究与比较者的回顾性队列研究的幼稚比较。关键的临床证据和经济模型方法与CAR-T和适应症基本一致,虽然结果各不相同。值得注意的是,所有增量QALY变化很大(获得3.67-10.6QALY),而DLBCL的变异较小(1.21-1.97[tisagenlecleucel],1.97-3.40[axicabtagene])。成本和结果的折扣各不相同,所有中的tisagenlecleucel产生的最高QALY(10.95)与最低贴现率(1.5%)相关,反之亦然(4.97QALY;5%贴现率)。推断总体生存数据的方法各不相同,即使使用了相同的经验数据。
建模,与成人相比,年轻患者的长期治疗获益可能与更大的不确定性相关,因为细胞和基因疗法具有潜在的终身获益.这反映了HTA机构确定的与单臂相关的方法学挑战,短期研究。
The objective of this
review was to identify sources of variability in cost-effectiveness analyses of chimeric antigen receptor T-cell (CAR-T) therapies, tisagenlecleucel and axicabtagene ciloleucel, evaluated by health technology assessment (HTA) agencies, focusing on young compared with older patients.
HTA evaluations in pediatric acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma (DLBCL) were included from Australia, Canada, England, Norway, and the United States. Key clinical evidence, economic approach, and outcomes (costs, quality-adjusted life-years [QALYs] and incremental cost-effectiveness ratios) were summarized.
Fourteen HTA evaluations were identified (5 ALL, 9 DLBCL [4 tisagenlecleucel, 5 axicabtagene]). Analyses were naive comparisons of prospective single-arm studies for the CAR-Ts with retrospective cohort studies for the comparators. Key clinical evidence and economic model approaches were generally consistent by CAR-T and indication, although outcomes varied. Notably, incremental QALYs varied substantially in ALL (3.67-10.6 QALYs gained), whereas variation in DLBCL was less (1.21-1.97 [tisagenlecleucel], 1.97-3.40 [axicabtagene]). Discounting of costs and outcomes varied, with the highest QALYs generated for tisagenlecleucel in ALL (10.95) associated with the lowest discount rate (1.5%) and vice versa (4.97 QALYs; 5% discount rate). The approach to extrapolation of overall survival data varied, even where the same empirical data were used.
Modeled, long-term treatment benefit in young patients may be associated with greater uncertainty compared with adults because of potential life-long benefits with cell and gene therapies. This reflects the methodological challenges identified by HTA agencies associated with single-arm, short-term studies.