1Veterans Affairs Palo Alto Health Care System, Palo Alto, CA.
2Stanford University, Stanford, CA.
J Clin Oncol. 2019 Aug 20;37(24):2105-2119. doi: 10.1200/JCO.18.02079. Epub 2019 Jun 3.
Two anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies are approved for diffuse large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel; each costs $373,000. We evaluated their cost effectiveness.
We used a decision analytic Markov model informed by recent multicenter, single-arm trials to evaluate axi-cel and tisagenlecleucel in multiply relapsed/refractory, adult, diffuse large B-cell lymphoma from a US health payer perspective over a lifetime horizon. Under a range of plausible long-term effectiveness assumptions, each therapy was compared with salvage chemoimmunotherapy regimens and stem-cell transplantation. Main outcomes were undiscounted life years, discounted lifetime costs, discounted quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (3% annual discount rate). Sensitivity analyses explored uncertainty.
In an optimistic scenario, assuming a 40% 5-year progression-free survival (PFS), axi-cel increased life expectancy by 8.2 years at $129,000/QALY gained (95% uncertainty interval, $90,000 to $219,000). At a 30% 5-year PFS, improvements in life expectancy were more modest (6.4 years) and expensive ($159,000/QALY gained [95% uncertainty interval, $105,000 to $284,000]). In an optimistic scenario, assuming a 35% 5-year PFS, tisagenlecleucel increased life expectancy by 4.6 years at $168,000/QALY gained (95% uncertainty interval, $105,000 to $414,000/QALY). At a 25% 5-year PFS, improvements in life expectancy were smaller (3.4 years) and more expensive ($223,000/QALY gained [95% uncertainty interval, $123,000 to $1,170,000/QALY]). Administering CAR-T to all indicated patients would increase US health care costs by approximately $10 billion over 5 years. Price reductions to $250,000 and $200,000, respectively, or payment only for initial complete response (at current prices) would allow axi-cel and tisagenlecleucel to cost less than $150,000/QALY, even at 25% PFS.
At 2018 prices, it is possible that both CAR-T therapies meet a less than $150,000/QALY threshold. This depends on long-term outcomes compared with chemoimmunotherapy and stem-cell transplantation, which are uncertain. Widespread adoption would substantially increase non-Hodgkin lymphoma health care costs. Price reductions or payment for initial response would improve cost effectiveness, even with modest long-term outcomes.
两种抗 CD19 嵌合抗原受体 T 细胞（CAR-T）疗法已被批准用于弥漫性大 B 细胞淋巴瘤，即 axi-cel 和 tisagenlecleucel；每种疗法的费用均为 37.3 万美元。我们评估了它们的成本效益。
我们使用基于最近多中心、单臂试验的决策分析马尔可夫模型，从美国医保支付者的角度，在终生范围内评估了axi-cel 和 tisagenlecleucel 在多次复发/难治性成人弥漫性大 B 细胞淋巴瘤中的应用。在一系列合理的长期有效性假设下，每种疗法均与挽救性化疗免疫疗法方案和干细胞移植进行了比较。主要结果为无贴现寿命年、贴现寿命年成本、贴现质量调整寿命年（QALY）和增量成本效益比（3%的年度贴现率）。敏感性分析探讨了不确定性。
在乐观情况下，假设 5 年无进展生存率（PFS）为 40%，axi-cel 可使预期寿命延长 8.2 年，每 QALY 增加 129,000 美元（95%不确定区间为 90,000 美元至 219,000 美元）。在 30%的 5 年 PFS 假设下，对预期寿命的改善较为温和（6.4 年）且费用昂贵（每 QALY 增加 159,000 美元[95%不确定区间为 105,000 美元至 284,000 美元]）。在乐观情况下，假设 5 年 PFS 为 35%，tisagenlecleucel 可使预期寿命延长 4.6 年，每 QALY 增加 168,000 美元（95%不确定区间为 105,000 美元至 414,000 美元）。在 25%的 5 年 PFS 假设下，对预期寿命的改善较小（3.4 年）且费用更高（每 QALY 增加 223,000 美元[95%不确定区间为 123,000 美元至 1,170,000 美元]）。在 5 年内，向所有符合条件的患者使用 CAR-T 治疗将使美国医疗保健费用增加约 100 亿美元。分别将价格降至 25 万美元和 20 万美元，或仅对初始完全缓解（按现行价格）进行支付，将使 axi-cel 和 tisagenlecleucel 的成本低于 15 万美元/QALY，即使在 PFS 为 25%的情况下也是如此。
按照 2018 年的价格，这两种 CAR-T 疗法都有可能低于 15 万美元/QALY 的阈值。这取决于与化疗免疫疗法和干细胞移植相比的长期结果，而这些结果是不确定的。广泛采用将会大幅增加非霍奇金淋巴瘤的医疗保健费用。降低价格或仅对初始反应进行支付，即使在长期结果较为温和的情况下，也能提高成本效益。
