Lin John K, Lerman Benjamin J, Barnes James I, Boursiquot Brian C, Tan Yuan Jin, Robinson Alex Q L, Davis Kara L, Owens Douglas K, Goldhaber-Fiebert Jeremy D
John K. Lin, James I. Barnes, and Douglas K. Owens, Veterans Affairs Palo Alto Health Care System, Palo Alto; John K. Lin, James I. Barnes, Alex Q.L. Robinson, Douglas K. Owens, and Jeremy D. Goldhaber-Fiebert, Stanford University; and Benjamin J. Lerman, Brian C. Boursiquot, Yuan Jin Tan, and Kara L. Davis, Stanford University School of Medicine, Stanford, CA.
J Clin Oncol. 2018 Nov 10;36(32):3192-3202. doi: 10.1200/JCO.2018.79.0642. Epub 2018 Sep 13.
The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel was recently approved to treat relapsed or refractory pediatric acute lymphoblastic leukemia. With a one-time infusion cost of $475,000, tisagenlecleucel is currently the most expensive oncologic therapy. We aimed to determine whether tisagenlecleucel is cost effective compared with currently available treatments.
Markov modeling was used to evaluate tisagenlecleucel in pediatric relapsed or refractory acute lymphoblastic leukemia from a US health payer perspective over a lifetime horizon. The model was informed by recent multicenter, single-arm clinical trials. Tisagenlecleucel (under a range of plausible long-term effectiveness) was compared with blinatumomab, clofarabine combination therapy (clofarabine, etoposide, and cyclophosphamide), and clofarabine monotherapy. Scenario and probabilistic sensitivity analyses were used to explore uncertainty. Main outcomes were life-years, discounted lifetime costs, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (3% discount rate).
With an assumption of a 40% 5-year relapse-free survival rate, tisagenlecleucel increased life expectancies by 12.1 years and cost $61,000/QALY gained. However, at a 20% 5-year relapse-free survival rate, life-expectancies were more modest (3.8 years) and expensive ($151,000/QALY gained). At a 0% 5-year relapse-free survival rate and with use as a bridge to transplant, tisagenlecleucel increased life expectancies by 5.7 years and cost $184,000/QALY gained. Reduction of the price of tisagenlecleucel to $200,000 or $350,000 would allow it to meet a $100,000/QALY or $150,000/QALY willingness-to-pay threshold in all scenarios.
The long-term effectiveness of tisagenlecleucel is a critical but uncertain determinant of its cost effectiveness. At its current price, tisagenlecleucel represents reasonable value if it can keep a substantial fraction of patients in remission without transplantation; however, if all patients ultimately require a transplantation to remain in remission, it will not be cost effective at generally accepted thresholds. Price reductions would favorably influence cost effectiveness even if long-term clinical outcomes are modest.
抗CD19嵌合抗原受体T细胞疗法tisagenlecleucel最近被批准用于治疗复发或难治性小儿急性淋巴细胞白血病。Tisagenlecleucel单次输注成本为47.5万美元，是目前最昂贵的肿瘤治疗方法。我们旨在确定tisagenlecleucel与现有治疗方法相比是否具有成本效益。
采用马尔可夫模型，从美国医疗支付方的角度，对小儿复发或难治性急性淋巴细胞白血病患者的一生进行评估，以评价tisagenlecleucel的疗效。该模型以近期的多中心单臂临床试验为依据。将tisagenlecleucel（在一系列合理的长期疗效范围内）与博纳吐单抗、氯法拉滨联合疗法（氯法拉滨、依托泊苷和环磷酰胺）以及氯法拉滨单药疗法进行比较。采用情景分析和概率敏感性分析来探讨不确定性。主要结局指标为生命年、贴现终身成本、贴现质量调整生命年（QALY）和增量成本效益比（贴现率3%）。
假设5年无复发生存率为40%，tisagenlecleucel可使预期寿命延长12.1年，每获得一个QALY的成本为6.1万美元。然而，在5年无复发生存率为20%时，预期寿命增幅较小（3.8年），成本较高（每获得一个QALY需15.1万美元）。在5年无复发生存率为0%且用作移植桥梁的情况下，tisagenlecleucel可使预期寿命延长5.7年，每获得一个QALY的成本为18.4万美元。将tisagenlecleucel的价格降至20万美元或35万美元，将使其在所有情况下都能达到每QALY支付意愿阈值10万美元或15万美元。
Tisagenlecleucel的长期疗效是其成本效益的关键但不确定的决定因素。按其当前价格，如果它能使相当一部分患者在不进行移植的情况下保持缓解状态，那么tisagenlecleucel具有合理的价值；然而，如果所有患者最终都需要进行移植以维持缓解状态，那么按照普遍接受的阈值，它将不具有成本效益。即使长期临床结果一般，降价也将对成本效益产生有利影响。
