Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL
Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL
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DOI：
10.1038/leu.2017.65
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发表时间：
2017-10-01
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：
Munir, T.;Howard, D. R.;Hillmen, P.
Admire是一项多中心、随机对照、开放的IIB期优势试验，用于以前未经治疗的慢性淋巴细胞白血病。FIT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)。来自非随机II期试验的初步证据表明，在FCR(FCM-R)中加入米托蒽醌(FCM-R)可以提高缓解率。招募了215名患者，根据国际慢性淋巴细胞白血病标准研讨会评估完全缓解(CR)率的主要终点。次要终点为无进展生存期(PFS)、总生存期(OS)、总有效率、最小残留病(MRD)阴性和安全性。经统计学处理，CR率为69.8FCRvs69.3%FCM-R(调整后优势比OR：0.97；95%可信区间：0.53~1.79，P=0.932)。MRD阴性率FCR为59.3%，FCM-R为50.5%(调整后OR：0.7；95%CI：(0.39~1.26)，P=0.231)。在治疗期间，60.0%(n=129)的参与者接受粒细胞集落刺激因子作为中性粒细胞减少症的二级预防，FCR组的比例低于FCM-R组(56.1vs63.9%)。两种方案的毒性均可接受。治疗组对PFS和OS的改善无显著差异。试验证明，在FCR中加入米托蒽醌并没有增加反应的深度。口服FCR耐受性良好，与既往静脉化疗相比，在CR率和MRD阴性方面产生了令人印象深刻的反应。
ADMIRE was a multicenter, randomized-controlled, open, phase IIB superiority trial in previously untreated chronic lymphocytic leukemia. Conventional front-line therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). Initial evidence from non-randomized phase II trials suggested that the addition of mitoxantrone to FCR (FCM-R) improved remission rates. Two hundred and fifteen patients were recruited to assess the primary end point of complete remission (CR) rates according to International Workshop on Chronic Lymphocytic Leukemia criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity and safety. At final analysis, CR rates were 69.8 FCR vs 69.3% FCM-R (adjusted odds ratio (OR): 0.97; 95% confidence interval (CI): (0.53-1.79), P = 0.932). MRD-negativity rates were 59.3 FCR vs 50.5% FCM-R (adjusted OR: 0.70; 95% CI: (0.39-1.26), P = 0.231). During treatment, 60.0% (n = 129) of participants received granulocyte colony-stimulating factor as secondary prophylaxis for neutropenia, a lower proportion on FCR compared with FCM-R (56.1 vs 63.9%). The toxicity of both regimens was acceptable. There are no significant differences between the treatment groups for PFS and OS. The trial demonstrated that the addition of mitoxantrone to FCR did not increase the depth of response. Oral FCR was well tolerated and resulted in impressive responses in terms of CR rates and MRD negativity compared with historical series with intravenous chemotherapy.