Final results of EFC6663: a multicenter, international, phase 2 study of alvocidib for patients with fludarabine-refractory chronic lymphocytic leukemia.
Final results of EFC6663: a multicenter, international, phase 2 study of alvocidib for patients with fludarabine-refractory chronic lymphocytic leukemia.
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EFC6663的最终结果：一项多中心，国际，第2阶段研究的Alvocidib研究，针对氟达拉滨 - 难治性慢性淋巴细胞性白血病患者。
DOI：
10.1016/j.leukres.2015.02.001
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发表时间：
2015-05
影响因子：
2.7
通讯作者：
Grever MR
中科院分区：
文献类型：
--
作者：
Lanasa MC;Andritsos L;Brown JR;Gabrilove J;Caligaris-Cappio F;Ghia P;Larson RA;Kipps TJ;Leblond V;Milligan DW;Janssens A;Johnson AJ;Heerema NA;Bühler A;Stilgenbauer S;Devin J;Hallek M;Byrd JC;Grever MR
对基于氟达拉滨的疗法难治的慢性淋巴细胞白血病（CLL）患者使用目前可用的疗法具有较差的结果。阿伏西地的早期研究显示了在复发性CLL中的活性，包括具有高风险基因组特征的患者和对氟达拉滨难治的患者。进行了阿伏西地在氟达拉滨难治性CLL中的多中心、国际、II期研究以验证这些早期结果。患有氟达拉滨难治性CLL或由CLL引起的幼淋巴细胞白血病的患者用单药阿伏西地治疗。主要结局指标为总体缓解率，次要结局指标包括生存率、毒性反应和缓解持续时间。在34家临床试验机构入组了165例患者，159例患者接受了治疗。中位年龄为61岁，既往治疗的中位次数为4次，96%的患者为氟达拉滨难治性。评估者评估的总体缓解率为25%;大多数缓解为部分缓解。del（17 p）患者的缓解率较低（14%），但del（11 q）或巨大淋巴结病患者的缓解率相当。中位无进展生存期和总生存期分别为7.6和14.6个月。39例患者（25%）发生肿瘤溶解，13例接受血液透析。腹泻、疲劳和血液学毒性是常见的。阿伏西地在晚期氟达拉滨难治性CLL患者中具有临床活性。在具有高风险临床和基因组特征的患者中观察到临床应答。通过仔细监测，阿伏西地具有可管理的安全性。未来的研究应集中在发现临床反应和肿瘤溶解的生物标志物，并加强支持治疗措施。
Chronic lymphocytic leukemia (CLL) patients refractory to fludarabine based therapies have poor outcomes with currently available therapies. Early phase studies of alvocidib showed activity in relapsed CLL including patients with high risk genomic features and those refractory to fludarabine. A multi-center, international, phase II study of alvocidib in fludarabine refractory CLL was undertaken to validate these early results. Patients with fludarabine refractory CLL or prolymphocytic leukemia arising from CLL were treated with single agent alvocidib. The primary outcome measure was overall response rate, with secondary outcomes including survival, toxicity, and response duration. One hundred and sixty five patients were enrolled at 34 centers, and 159 patients were treated. The median age was 61 years, the median number of prior therapies was 4, and 96% of patients were fludarabine refractory. The investigator-assessed overall response rate was 25%; the majority of responses were partial. Response rates were lower among patients with del(17p) (14%), but equivalent in patients with del(11q) or bulky lymphadenopathy. Median progression free and overall survival were 7.6 and 14.6 months respectively. Tumor lysis occurred in 39 patients (25%), and 13 received hemodialysis. Diarrhea, fatigue, and hematologic toxicities were common. Alvocidib has clinical activity in patients with advanced, fludarabine refractory CLL. Clinical responses were observed in patients with high risk clinical and genomic features. With careful monitoring, alvocidib has a manageable safety profile. Future studies should focus on discovery of biomarkers of clinical response and tumor lysis, and enhanced supportive care measures.