Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL
Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL
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DOI：
10.1038/leu.2017.96
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发表时间：
2017-11-01
期刊：
影响因子：
11.4
通讯作者：
Hillmen, P.
中科院分区：
文献类型：
--
作者：
Howard, D. R.;Munir, T.;Hillmen, P.
ARCTIC 是一项针对既往未经治疗的慢性淋巴细胞白血病 (CLL) 的多中心、随机对照、开放、IIB 期非劣效性试验。健康患者的常规一线治疗是氟达拉滨、环磷酰胺和利妥昔单抗 (FCR)。该试验假设米托蒽醌与低剂量利妥昔单抗 (FCM-miniR) 联合使用不会劣于 FCR。总共招募了 200 名患者，根据 IWCLL 标准评估完全缓解 (CR) 率的主要终点。次要终点是无进展生存期（PFS）、总生存期（OS）、总缓解率、微小残留病（MRD）阴性、安全性和成本效益。该试验在预先计划的中期分析后结束。最终分析显示，CR 率为 76 FCR 与 55% FCM-miniR（调整后优势比：0.37；95% 置信区间：0.19-0.73）。 MRD 阴性率为 54% FCR，而 FCM-miniR 为 44%。与 FCR (41%) 相比，更多参与者在使用 FCM-miniR (49%) 时出现严重不良反应。治疗组之间的 PFS 和 OS 没有显着差异。 FCM-miniR 预计在整个生命周期内不会具有成本效益。总之，FCM-miniR 的耐受性不如 FCR，反应较差，MRD 阴性率较低，毒性增加，因此不会进入验证性试验。该试验表明，与静脉化疗的历史系列相比，口服 FCR 具有较高的缓解率。
ARCTIC was a multicenter, randomized-controlled, open, phase IIB non-inferiority trial in previously untreated chronic lymphocytic leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab (FCM-miniR) would be non-inferior to FCR. A total of 200 patients were recruited to assess the primary end point of complete remission (CR) rates according to IWCLL criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity, safety and cost-effectiveness. The trial closed following a pre-planned interim analysis. At final analysis, CR rates were 76 FCR vs 55% FCM-miniR (adjusted odds ratio: 0.37; 95% confidence interval: 0.19-0.73). MRD-negativity rates were 54 FCR vs 44% FCM-miniR. More participants experienced serious adverse reactions with FCM-miniR (49%) compared to FCR (41%). There are no significant differences between the treatment groups for PFS and OS. FCM-miniR is not expected to be cost-effective over a lifetime horizon. In summary, FCM-miniR is less well tolerated than FCR with an inferior response and MRD-negativity rate and increased toxicity, and will not be taken forward into a confirmatory trial. The trial demonstrated that oral FCR yields high response rates compared to historical series with intravenous chemotherapy.