Liverpool Reviews and Implementation Group, Sherrington Buildings, University of Liverpool, Liverpool, UK.
Health Technol Assess. 2009 Sep;13 Suppl 2:41-8. doi: 10.3310/hta13suppl2/06.
This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma (NHL), in accordance with the licensed indication, based upon the evidence submission from Roche Products Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submitted clinical evidence included two randomised controlled trials [European Organisation for Research and Treatment of Cancer (EORTC) and German Low Grade Lymphoma Study Group - Fludarabine, Cyclophosphamide and Mitoxantrone and (GLSG-FCM)] comparing the clinical effects of chemotherapy with or without rituximab in the induction of remission at first or second relapse and the clinical benefits of rituximab maintenance therapy versus the NHS's current clinical practice of observation for follicular lymphoma (FL) patients. Both trials showed that in patients with relapsed FL the addition of rituximab to chemotherapy induction treatment increased overall response rates. Furthermore, rituximab maintenance therapy increased the median length of remission when compared with observation only. Safety data from the two trials showed that while the majority of patients reported some adverse events, the number of patients withdrawing from treatment in the EORTC trial was low, with rates not being reported for the GLSG-FCM trial. The most commonly reported adverse events were blood/bone marrow toxicity, skin rashes and allergies. The ERG reran the manufacturer's economic model after altering several of the assumptions and parameter values in order to recalculate the cost-utility ratios, quality-adjusted life-years (QALYs) and estimates of benefits. The manufacturer reported that maintenance therapy with rituximab was cost-effective compared with observation against commonly applied thresholds, with an incremental cost-effectiveness ratio of 7721 pounds per QALY gained. The greatest clinical effectiveness is achieved by R-CHOP followed by rituximab maintenance (R-CHOP>R) and this treatment strategy had the greatest probability of being cost-effective for a QALY of approximately 18,000 pounds or greater. The guidance issued by NICE as a result of the STA states that in people with relapsed stage III or IV follicular NHL, rituximab is now an option in combination with chemotherapy to induce remission or alone as maintenance therapy during remission. Rituximab monotherapy is also an option for people with relapsed or refractory disease when all alternative treatment options have been exhausted.
本文根据罗氏产品有限公司向英国国家卫生与临床优化研究所（NICE）提交的证据，概述了许可适应症范围内，利妥昔单抗治疗复发性或难治性 III 或 IV 期滤泡性非霍奇金淋巴瘤（NHL）的疗效和成本效益的证据审查组报告。该提交的临床证据包括两项随机对照试验[欧洲癌症研究与治疗组织（EORTC）和德国低级别淋巴瘤研究组-氟达拉滨、环磷酰胺和米托蒽醌（GLSG-FCM）]，比较了在首次或第二次复发时使用化疗联合或不联合利妥昔单抗诱导缓解的临床效果，以及利妥昔单抗维持治疗相对于 NHS 目前滤泡性淋巴瘤（FL）患者观察的临床获益。两项试验均表明，在复发 FL 患者中，与单纯化疗诱导治疗相比，利妥昔单抗的加入增加了总体缓解率。此外，与单纯观察相比，利妥昔单抗维持治疗延长了缓解的中位时间。两项试验的安全性数据表明，虽然大多数患者报告有一些不良反应，但 EORTC 试验中退出治疗的患者人数较少，而 GLSG-FCM 试验未报告退出率。最常见的不良反应是血液/骨髓毒性、皮疹和过敏。ERG 对制造商的经济模型进行了重新计算，改变了几个假设和参数值，以重新计算成本效用比、质量调整生命年（QALY）和收益估计。制造商报告称，与观察相比，利妥昔单抗维持治疗具有成本效益，符合常见的应用阈值，增量成本效果比为每获得一个 QALY 增加 7721 英镑。R-CHOP 联合利妥昔单抗维持治疗的临床效果最佳（R-CHOP>R），且对于 QALY 约为 18000 英镑或更高的情况，这种治疗策略最有可能具有成本效益。NICE 基于 STA 发布的指南指出，在复发性 III 或 IV 期滤泡性 NHL 患者中，利妥昔单抗现在是联合化疗诱导缓解的一种选择，或在缓解期单独作为维持治疗。当所有其他治疗选择都已用尽时，利妥昔单抗单药治疗也是复发性或难治性疾病的一种选择。
