Lanasa Mark C, Andritsos Leslie, Brown Jennifer R, Gabrilove Janice, Caligaris-Cappio Federico, Ghia Paolo, Larson Richard A, Kipps Thomas J, Leblond Veronique, Milligan Donald W, Janssens Ann, Johnson Amy J, Heerema Nyla A, Bühler Andreas, Stilgenbauer Stephan, Devin Jeanne, Hallek Michael, Byrd John C, Grever Michael R
Duke University Medical Center, Durham, NC, United States.
The Ohio State University, Columbus, OH, United States.
Leuk Res. 2015 May;39(5):495-500. doi: 10.1016/j.leukres.2015.02.001. Epub 2015 Feb 7.
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 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. Future studies should focus on discovery of biomarkers of clinical response and tumor lysis, and enhanced supportive care measures.
阿沃西地布的早期研究表明其对复发的慢性淋巴细胞白血病（CLL）有活性，包括具有高风险基因组特征的患者以及对氟达拉滨耐药的患者。开展了一项关于阿沃西地布治疗氟达拉滨耐药CLL的多中心、国际II期研究，以验证这些早期结果。患有氟达拉滨耐药CLL或由CLL引起的原淋巴细胞白血病的患者接受阿沃西地布单药治疗。主要结局指标是总缓解率，次要结局包括生存率、毒性和缓解持续时间。共纳入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%的患者对氟达拉滨耐药。研究者评估的总缓解率为25%；大多数缓解为部分缓解。del(17p)患者的缓解率较低（14%），但del(11q)或有巨大淋巴结病的患者缓解率相当。中位无进展生存期和总生存期分别为7.6个月和14.6个月。39例患者（25%）发生肿瘤溶解，13例接受了血液透析。腹泻、疲劳和血液学毒性很常见。阿沃西地布对晚期、氟达拉滨耐药的CLL患者具有临床活性。未来的研究应侧重于发现临床反应和肿瘤溶解的生物标志物，以及加强支持性护理措施。
