Sol Price School of Public Policy and Leonard D. Schaeffer Center for Health Policy and Economics, University of Southern California, Los Angeles, CA, USA.
Novartis Pharmaceuticals, Basel, Switzerland.
Value Health. 2022 Aug;25(8):1344-1351. doi: 10.1016/j.jval.2022.02.007. Epub 2022 Mar 24.
This study aimed to quantify the value of reducing chimeric antigen receptor T-cell (CAR-T) treatment wait times on patients with refractory and relapsed aggressive blood cancer who can newly gain access to treatment or access treatment earlier in their disease course.
Using data from the JULIET clinical trial, we first identified the number of additional patients with diffuse large B-cell lymphoma that would have been treated with tisagenlecleucel CAR-T therapy if wait times were shortened. For these patients, we estimated mortality benefits using literature estimates of CAR-T effectiveness. Next, among patients who already received CAR-T, we estimated tumor burden progression over time using a linear probability regression model. The primary outcome variable was an indicator for having above-normal lactate dehydrogenase, and we controlled for time, use of bridging therapy, and time-invariant patient characteristics. The regression results, along with literature estimates relating lactate dehydrogenase to CAR-T effectiveness, were used to compute the survival benefits of earlier CAR-T treatment.
Reducing wait times by 2 months increased the number of eligible patients receiving CAR-T by at least 10.7%. For patients already receiving tisagenlecleucel CAR-T, a 2-month reduction in wait times generated a 3.3% increase in survival gains per treated patient. Thus, among patients seeking treatment, the combined treatment efficacy increased by 14%, with approximately one-quarter of survival benefits accruing to existing patients receiving faster treatment.
Delays affected not only access to CAR-T treatments but also treatment effectiveness. Our results highlight the survival benefits of expediting treatment access and may help explain some observed differences in CAR-T effectiveness across countries.
本研究旨在量化减少嵌合抗原受体 T 细胞(CAR-T)治疗等待时间对新获得治疗或在疾病早期获得治疗的难治性和复发性侵袭性血液癌患者的价值。
利用 JULIET 临床试验的数据,我们首先确定了如果缩短等待时间,会有多少新的弥漫性大 B 细胞淋巴瘤患者接受 tisagenlecleucel CAR-T 治疗。对于这些患者,我们使用 CAR-T 有效性的文献估计来估计死亡率获益。接下来,对于已经接受 CAR-T 治疗的患者,我们使用线性概率回归模型估计随时间推移肿瘤负担的进展情况。主要结果变量是乳酸脱氢酶升高的指标,我们控制了时间、桥接治疗的使用以及时间不变的患者特征。回归结果以及与乳酸脱氢酶与 CAR-T 有效性相关的文献估计值,用于计算更早接受 CAR-T 治疗的生存获益。
将等待时间缩短 2 个月,至少增加了 10.7%接受 CAR-T 治疗的合格患者数量。对于已经接受 tisagenlecleucel CAR-T 治疗的患者,等待时间缩短 2 个月可使每位治疗患者的生存获益增加 3.3%。因此,在寻求治疗的患者中,联合治疗效果增加了 14%,其中大约四分之一的生存获益归因于接受更快治疗的现有患者。
延迟不仅影响了 CAR-T 治疗的获得,还影响了治疗的有效性。我们的研究结果强调了加快治疗获得的生存获益,这可能有助于解释不同国家之间观察到的 CAR-T 有效性差异。