The clinical effectiveness agency for England and Wales says that it will probably recommend rituximab in the coming months for the maintenance treatment of follicular non-Hodgkins lymphoma.
Maintenance therapy with rituximab (MabThera, Roche) would follow initial treatment with rituximab and chemotherapy drugs – already the standard first-line treatment for follicular non-Hodgkins lymphoma (NHL) in U.K. clinical practice – for people whose disease has responded.
The maintenance strategy, intended to prolong progression-free survival before second-line chemotherapy is warranted, provides an alternative to the current “watch-and-wait” approach to disease progression, the National Institute for Health and Clinical Excellence said Dec. 3.
Although rituximab maintenance treatment carries some adverse effects, including injection-related infections and flu-like symptoms, these are considered to be more manageable than those of chemotherapy. The NICE reviewers noted that “chemotherapy is considered to be more toxic than rituximab and may cause symptoms that are worse than those caused by follicular lymphoma itself,” whereas people treated with rituximab maintenance in clinical trials “were able to continue with their normal daily routine.”
In one randomized open-label phase III trial (n=1,193) submitted by the manufacturer to NICE but whose results have yet to be published, rituximab maintenance after induction therapy was associated with a lower risk of disease progression compared with a watch-and-wait approach following induction therapy.
After a median of 25 months, the risk of disease progression was halved in the rituximab maintenance arm (hazard ratio [HR], 0.50; 95% CI, 0.39-0.64; P < .0001), compared with the watch-and-wait arm. Overall survival could not be established after 38 months because too few patients had died in either arm.
NICE also reviewed findings from a smaller open-label study submitted by the manufacturer (J. Clin. Oncol. 2010;28:2853-8) that enrolled 465 people with resistant or relapsed follicular NHL. In it, maintenance treatment with rituximab (following induction chemotherapy with rituximab and other agents) was also shown to prolong progression-free survival over watching and waiting (median 3.7 years compared with 1.3 years). However, 5-year overall survival was not significantly different (74% in the rituximab maintenance arm and 64% in the observation arm).
Rituximab is a humanized monoclonal antibody that works by targeting CD20 surface antigen of mature B-cell lymphocytes. It is delivered as an intravenous infusion. Maintenance therapy with rituximab is 375 mg/m2 body surface area, once every 2 months, following the final dose of induction therapy and continues until disease progression or up to 2 years.
Estimated incremental cost-effectiveness ratios for rituximab maintenance varied by scenario in NICE’s Dec. 3 draft guidance, but most hovered between £20,000 and £30,000 per quality-adjusted life year. NICE said that the treatment “may be within the range that is consistent with an appropriate use of NHS resources” but that more detailed assessments were needed. Two years of rituximab maintenance treatment costs approximately £14,669, NICE said.
Specifically, the reviewers said that they would need more cost-effectiveness data before rituximab could be formally recommended. They asked the manufacturer to perform breakout analyses on patients 60-65 years old at the start of treatment, as patients in the largest clinical trial tended to be younger. They also asked for better modeling on cost effectiveness related to overall survival, for a shorter duration of clinical benefit from rituximab maintenance than the manufacturer presented, and for “utility gains associated with delaying the need for chemotherapy.”
Comments on rituximab maintenance close on Jan. 7, and further guidance is expected in February.
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英格兰和威尔士的临床疗效评价机构(NICE)称其在接下来的几个月中极有可能推荐将利妥昔单抗用作滤泡性非霍奇金淋巴瘤(NHL)的维持治疗。
利妥昔单抗是一种人源化单克隆抗体，通过攻击成熟B淋巴细胞中的CD20表面抗原发挥作用，以静脉注射方式给药。在英国，继利妥昔单抗(美罗华，罗氏)联合化疗药物初始治疗后行利妥昔单抗维持治疗已成为病情缓解的滤泡性非霍奇金淋巴瘤(NHL)患者的标准一线治疗方案。
在利妥昔单抗生产厂家向英国国家卫生与临床优化研究所(NICE)提交的一项III期开放性随机临床试验(n=1,193) (试验结果尚未公布)中，与在诱导治疗后采取观望策略相比，采用利妥昔单抗维持治疗可降低疾病进展的风险。在25个月的中位治疗期后，与观望组相比，利妥昔单抗维持治疗组的疾病进展风险降低50%(风险比[HR], 0.50; 95% CI, 0.39~0.64; P<0.0001)。由于两组中的死亡人数极少，故无法确定38个月后的总生存率。另外，NICE还审查了一项由生产厂家提交的规模较小的开放性研究的结果(J. Clin. Oncol. 2010;28:2853-8)，其受试者为465例难治性滤泡性NHL或滤泡性NHL复发患者。其结果亦表明，相对于观望策略而言，在使用利妥昔单抗和其他药物进行诱导治疗之后采用利妥昔单抗维持治疗可延长无进展生存期(中位无进展生存期分别为3.7年和1.3年)，但两组在5年总生存率方面无显著差异(利妥昔单抗维持治疗组为74%，观望组为64%)。
尽管利妥昔单抗维持治疗可产生许多副作用，包括注射相关的感染和流感样症状，但较化疗的副作用更易于处理，在临床试验中接受利妥昔单抗维持治疗的患者“可以继续进行正常的日常生活”。
NICE于12月3日表示，利妥昔单抗维持治疗策略可延长适合行二线化疗前的无进展生存期，使医生大可不必采取当前对待疾病进展所采取的“观望”策略。其维持治疗量为375 mg/m2体表面积，在末次诱导治疗之后给药，每2个月给药1次，并持续至疾病进展或持续2年。根据指南草案，利妥昔单抗维持治疗的增量成本效益比估计值因具体情况而异，大多在20,000英镑~30,000英镑/质量调整生命年之间波动，可能符合英国国家医疗服务系统(NHS)医疗资源的统筹调配要求，但还需要更多详细的评估结果。利妥昔单抗维持治疗2年的成本接近14,669英镑。
关于利妥昔单抗维持治疗的评论截止到2011年1月7日，进一步的指南预计将于2011年2月出台。
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