BACKGROUND Several strategies are available for the initial treatment of advanced-stage Hodgkin lymphoma, but the optimal strategy in terms of cost-effectiveness is unclear. The aim of this study was to compare the quality-adjusted effectiveness and costs of five modern treatment options for transplantation-eligible patients with newly diagnosed advanced-stage Hodgkin lymphoma. METHODS A Markov decision-analytic model was developed using a 20-year time horizon. Five of the most common treatment approaches were selected based on clinical experience and expert opinion: (1) six cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), including data from the HD2000 trial, Viviani and colleagues, and EORTC trial; (2) six cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP; from the HD15 trial or PET-adapted as in the HD18 trial, two initial cycles of BEACOPP followed by four additional cycles for patients with a positive PET and either two or four additional cycles of BEACOPP for patients with a negative PET); (3) PET-adapted escalation (as in the RATHL trial, two cycles of standard ABVD chemotherapy followed by an additional four cycles of ABVD or AVD in PET-negative patients and four cycles of BEACOPP in PET-positive patients); (4) six cycles of brentuximab vedotin, doxorubicin, vinblastine, dacarbazine (A-AVD) or ABVD as in the Echelon-1 trial; and (5) PET-adapted de-escalation (as in the AHL2011 trial, two cycles of BEACOPP followed by PET2 scan; PET-positive patients received two additional BEACOPP cycles and PET-negative patients received two cycles of ABVD; at PET4, PET-negative patients completed two further cycles of either ABVD or BEACOPP depending on what they received after PET2, and PET-positive patients received salvage therapy). Note that all uses of BEACOPP in these strategies were BEACOPPescalated. The randomised groups of interest from these studies comprised 4255 patients enrolled between April, 2000, and January, 2016. Baseline probability estimates and utilities were derived from the included trials in addition to a systematic review of published studies. A Canadian public health payer's perspective was considered (CAN$1=US$0·74) and adjusted for inflation for 2018. All costs and benefits were discounted by 1·5% per year because life-years now are more valuable than future potential life-years. FINDINGS Probabilistic analyses (10 000 simulations) showed that, for a willingness-to-pay threshold of CAN$50 000, a PET-adapted de-escalation strategy based on AHL2011 was more cost-effective 87% of the time. This strategy had the highest number of life-years (14·6 years [95% CI 13·7-15·1]) and quality-adjusted life years (13·2 years [95% CI 10·2-14·4]), and the lowest direct costs ($53 129 [95% CI 31 914-94 446]) compared with the other treatment regimens. Sensitivity analyses showed that the model was robust to key variables, including probability of treatment-related mortality, relapse, frequency of secondary malignancy, death from secondary malignancy, and probability of infertility after BEACOPP. INTERPRETATION Our results suggest that, when considering cost, effectiveness, and short and long-term toxicities, the preferred treatment strategy for patients with newly diagnosed advanced-stage Hodgkin lymphoma is the PET-adapted de-escalation regimen starting with BEACOPP and de-escalating to ABVD as appropriate. Although our findings do not provide an absolute best treatment approach for clinicians to follow for all patients, they can contribute to shared decision making between patients and treating physicians. FUNDING None.

中文翻译：

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一线治疗方案对晚期霍奇金淋巴瘤患者的成本效益：一项模型研究。

背景技术有几种策略可用于晚期霍奇金淋巴瘤的初始治疗，但就成本效益而言，最佳策略尚不清楚。这项研究的目的是比较适合移植的新诊断晚期霍奇金淋巴瘤患者的五种现代治疗方案的质量调整效果和成本。方法使用20年的时间范围开发了马尔可夫决策分析模型。根据临床经验和专家意见选择了五种最常见的治疗方法：（1）阿霉素，博来霉素，长春碱，达卡巴嗪（ABVD）的六个周期，包括HD2000试验，Viviani及其同事和EORTC试验的数据；（2）博来霉素，依托泊苷，阿霉素，环磷酰胺，长春新碱，丙卡巴嗪和泼尼松的六个周期（BEACOPP；从HD15试验或适应于HD18试验的PET适应性研究，PET阳性的患者先进行两个初始BEABEP周期，然后再进行四个附加周期，PET阴性的患者进行两个或四个额外的BEACOPP周期）；（3）PET适应性升级（如RATHL试验中一样，PET阴性患者接受2周期的标准ABVD化疗，然后再接受4周期的ABVD或AVD，PET阳性患者进行4周期的BEACOPP）；（4）与Echelon-1试验相同，六个周期的brentuximab vedotin，阿霉素，长春碱，达卡巴嗪（A-AVD）或ABVD；（5）适合PET的降级（如在AHL2011试验中一样，进行两个周期的BEACOPP继之以PET2扫描； PET阳性的患者接受两个额外的BEACOPP周期，PET阴性的患者接受两个ABVD周期；在PET4，PET阴性患者根据在PET2之后接受的治疗再完成ABVD或BEACOPP的另外两个周期，PET阳性患者接受挽救治疗。请注意，在这些策略中对BEACOPP的所有使用都经过BEACOPPescaled。这些研究的随机分组感兴趣的患者包括2000年4月至2016年1月之间的4255例患者。除了对已发表研究进行系统评价之外，基线概率估计值和效用均来自所纳入的试验。考虑了加拿大公共卫生支付者的观点（1加元= 0.74加元），并根据2018年的通货膨胀进行了调整。所有成本和收益每年都折现1·5％，因为生命年现在比未来的潜在生命更有价值-年份。结果概率分析（10000次模拟）表明，如果愿意支付的门槛为5万加元，则基于AHL2011的PET自适应降级策略在87％的时间内更具成本效益。该策略具有最高的生命年数（14·6年[95％CI 13·7-15·1]）和质量调整的生命年（13·2年[95％CI 10·2-14·4] ]），并且与其他治疗方案相比，直接费用最低（$ 53 129 [95％CI 31 914-94 446]）。敏感性分析表明，该模型对关键变量具有鲁棒性，这些变量包括与治疗相关的死亡率，复发，继发性恶性肿瘤的频率，继发性恶性肿瘤死亡以及BEACOPP后不孕的可能性。解释我们的结果表明，在考虑成本，有效性以及短期和长期毒性时，对于新诊断的晚期霍奇金淋巴瘤患者，首选的治疗策略是PET适应降级方案，从BEACOPP开始并酌情降级为ABVD。尽管我们的发现并未为临床医生提供针对所有患者的绝对最佳治疗方法，但它们可有助于患者与主治医生之间的共同决策。资金无。