在美国，用 axicabtagene ciloleucel 治疗复发/难治性 3L+滤泡性淋巴瘤与 mosunetuzumab 的成本效益比较。

INTRODUCTION: Novel therapies for 3L+ relapsed/refractory (r/r) follicular lymphoma (FL) have been approved recently by the US Food and Drug Administration including anti-CD19 CAR-T therapies such as axicabtagene ciloleucel (axi-cel) and CD20 × CD3 T-cell-engaging bispecific monoclonal antibodies such as mosunetuzumab (mosun). The objective of this study was to assess the cost-effectiveness of axi-cel compared to mosun in 3L+ r/r FL patients from a US third-party payer perspective. METHODS: A three-state (progression-free, progressed disease, and death) partitioned-survival model was used to compare two treatments over a lifetime horizon in a hypothetical cohort of US adults (age ≥18) receiving 3L+ treatment for r/r FL. ZUMA-5 and GO29781 trial data were used to inform progression-free survival (PFS) and overall survival (OS). Mosun survival was modeled via hazard ratios (HRs) applied to axi-cel survival curves. The PFS HR value was estimated via a matching-adjusted indirect comparison (MAIC) based on mosun pseudo-individual patient data and adjusted axi-cel data to account for trial populations differences. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analyses (PSA) were conducted. Scenario analyses included: 1) the mosun HRs were applied to the weighted (adjusted) ZUMA-5 24-month data to most exactly reflect the MAIC, 2) mosun HR values were applied to axi-cel 48-month follow-up data, and 3) recent axi-cel health state utility values in diffuse large B-cell lymphoma patients. RESULTS: The analysis estimated increases of 1.82 LY and 1.89 QALY for axi-cel compared to mosun. PFS for axi-cel patients was 6.42 LY vs. 1.60 LY for mosun. Increase of $257,113 in the progression-free state was driven by one-time axi-cel treatment costs. Total incremental costs for axi-cel were $204,377, resulting in an ICER of $108,307/QALY gained. The OWSA led to ICERs ranging from $240,255 to $75,624, with all but two parameters falling below $150,000/QALY. In the PSA, axi-cel had an 64% probability of being cost-effective across 5,000 iterations using a $150,000 willingness-to-pay threshold. Scenarios one and two resulted in ICERs of $105,353 and $102,695, respectively. DISCUSSION: This study finds that axi-cel is cost-effective compared to mosun at the commonly cited $150,000/QALY US willingness-to-pay threshold, with robust results across a range of sensitivity analyses accounting for parameter uncertainty.

简介：最近，美国食品和药物管理局批准了几种新的治疗 3L+复发/难治性（r/r）滤泡性淋巴瘤（FL）的疗法，包括抗 CD19 CAR-T 疗法，如 axi-cel 和 CD20×CD3 T 细胞结合双特异性单克隆抗体，如 mosunetuzumab（mosun）。本研究旨在从美国第三方支付者的角度评估 axi-cel 与 mosun 在 3L+r/r FL 患者中的成本效益。

方法：使用三状态（无进展、疾病进展和死亡）分区生存模型，在接受 3L+r/r FL 治疗的美国成年人（年龄≥18 岁）的假设队列中，比较两种治疗方法在终身内的疗效。ZUMA-5 和 GO29781 试验数据用于报告无进展生存期（PFS）和总生存期（OS）。mosun 的生存通过应用于 axi-cel 生存曲线的风险比（HRs）进行建模。通过匹配调整的间接比较（MAIC）估计 PFS HR 值，该比较基于 mosun 伪个体患者数据，并调整 axi-cel 数据以考虑试验人群差异。进行了单因素敏感性分析（OWSA）和概率敏感性分析（PSA）。情景分析包括：1）将 mosun HRs 应用于加权（调整）ZUMA-5 24 个月数据，以最准确地反映 MAIC；2）将 mosun HRs 应用于 axi-cel 的 48 个月随访数据；3）最近在弥漫性大 B 细胞淋巴瘤患者中使用 axi-cel 健康状态效用值。

结果：分析估计 axi-cel 比 mosun 增加了 1.82 年的生存期和 1.89 个质量调整生命年（QALY）。axi-cel 患者的 PFS 为 6.42 年，而 mosun 为 1.60 年。无进展状态下一次性 axi-cel 治疗费用增加了 257113 美元。axi-cel 的总增量成本为 204377 美元，导致增量成本效益比（ICER）为 108307 美元/QALY。OWSA 导致 ICER 范围为 240255 美元至 75624 美元，除了两个参数外，所有参数均低于 150000 美元/QALY。在 PSA 中，在 5000 次迭代中，使用 150000 美元的支付意愿阈值，axi-cel 具有 64%的成本效益概率。方案一和方案二的 ICER 分别为 105353 美元和 102695 美元。

讨论：本研究发现，在通常引用的 150000 美元/QALY 的美国支付意愿阈值下，axi-cel 与 mosun 相比具有成本效益，在考虑参数不确定性的一系列敏感性分析中具有稳健的结果。