Flowers Christopher R, Brown Jennifer R, Rosenthal Hilary, Stock Wendy, Katzen Harvey I, Cohen Jonathon B, Sinha Rajni, Lakhanpal Shailendra, Leis Jose F, Waller Edmund K, Jaye David L
Winship Cancer Institute, Emory University, Atlanta, GA.
Dana-Farber Cancer Institute, Boston, MA.
Clin Lymphoma Myeloma Leuk. 2015 Nov;15(11):694-8. doi: 10.1016/j.clml.2015.07.640. Epub 2015 Aug 5.
Alemtuzumab is effective in fludarabine-refractory patients with chronic lymphocytic leukemia. We performed a phase 2 study of alemtuzumab in combination with fludarabine in patients with relapsed disease.
Patients received alemtuzumab and fludarabine daily on days 1 to 5 of a 28-day cycle for up to 6 cycles with the primary objective of determining the rate of complete response. Of 60 enrolled patients, 51 had previously received fludarabine, and 60% had received 3 or more prior therapies.
Five patients experienced complete response (8.3%) and 12 experienced partial response, yielding an overall response rate of 28.3% for the intention-to-treat population. Among the 41 patients who completed at least 4 cycles of therapy, the complete response rate was 20%. Median progression-free survival was 211 days. Forty-seven percent of patients experienced cytomegalovirus viremia, including 4 patients with symptomatic cytomegalovirus disease. All patients responded to antiviral therapy.
Despite some evidence of efficacy in this setting, the primary end point for the study was not met. In the era of targeted agents that are well tolerated, the combination of fludarabine and alemtuzumab should be used rarely for a select group of fit patients who are refractory to standard therapies.
阿仑单抗对氟达拉滨难治的慢性淋巴细胞白血病患者有效。我们开展了一项阿仑单抗联合氟达拉滨治疗复发疾病患者的2期研究。
患者在28天周期的第1至5天每天接受阿仑单抗和氟达拉滨治疗，最多6个周期，主要目的是确定完全缓解率。在60例入组患者中，51例曾接受过氟达拉滨治疗，60%的患者曾接受过3种或更多的前期治疗。
5例患者获得完全缓解（8.3%），12例患者获得部分缓解，意向性治疗人群的总缓解率为28.3%。在41例完成至少4个周期治疗的患者中，完全缓解率为20%。无进展生存期的中位数为211天。47%的患者出现巨细胞病毒血症，其中4例患有症状性巨细胞病毒病。所有患者对抗病毒治疗均有反应。
尽管在此情况下有一些疗效证据，但该研究的主要终点未达到。在耐受性良好的靶向药物时代，氟达拉滨和阿仑单抗联合应用应很少用于对标准治疗难治的特定合适患者群体。
