Department of Hematology, Rigshospitalet, Copenhagen, Denmark;
Department of Hematology, Erasmus Medisch Centrum, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands;
Blood. 2014 May 22;123(21):3255-62. doi: 10.1182/blood-2014-01-547737. Epub 2014 Apr 15.
The randomized Haemato Oncology Foundation for Adults in The Netherlands 68 phase 3 trial compared front-line chemotherapy with chemotherapy plus the CD52 monoclonal antibody alemtuzumab for high-risk chronic lymphocytic leukemia, defined as at least 1 of the following: unmutated immunoglobulin heavy chain genes, deletion 17p or 11q, or trisomy 12. Fit patients were randomized to receive either 6 28-day cycles of oral FC chemotherapy (days 1 through 3: fludarabine 40 mg/m(2) per day and cyclophosphamide 250 mg/m(2) per day: n = 139) or FC plus subcutaneous alemtuzumab 30 mg day 1 (FCA, n = 133). FCA prolonged the primary end point, progression-free survival (3-year progression-free survival 53 vs 37%, P = .01), but not the secondary end point, overall survival (OS). However, a post hoc analysis showed that FCA increased OS in patients younger than 65 years (3-year OS 85% vs 76%, P = .035). FCA also increased the overall response rate (88 vs 78%, P = .036), and the bone marrow minimal residual disease-negative complete remission rate (64% vs 43%, P = .016). Opportunistic infections were more frequent following FCA, but without an increase in treatment related mortality (FCA: 3.8%, FC: 4.3%). FCA improves progression-free survival in high-risk chronic lymphocytic leukemia. As anticipated, FCA is more immunosuppressive than FC, but with due vigilance, does not lead to a higher treatment-related mortality. This study was registered at www.trialregister.nl as trial no. NTR529.
荷兰血液肿瘤成人研究基金会 68 期 3 期随机试验比较了一线化疗联合化疗加 CD52 单克隆抗体阿仑单抗治疗高危慢性淋巴细胞白血病，高危定义为以下至少 1 项：未突变的免疫球蛋白重链基因、缺失 17p 或 11q 或三体 12。符合条件的患者被随机分配接受 6 个 28 天周期的口服 FC 化疗（第 1 至 3 天：每天氟达拉滨 40mg/m2 和环磷酰胺 250mg/m2：n = 139）或 FC 加皮下阿仑单抗 30mg 第 1 天（FCA，n = 133）。FCA 延长了主要终点，无进展生存期（3 年无进展生存率 53%比 37%，P =.01），但不是次要终点，总生存期（OS）。然而，事后分析显示 FCA 增加了年龄小于 65 岁的患者的 OS（3 年 OS 为 85%比 76%，P =.035）。FCA 还增加了总缓解率（88%比 78%，P =.036）和骨髓微小残留疾病阴性完全缓解率（64%比 43%，P =.016）。FCA 后机会性感染更频繁，但治疗相关死亡率没有增加（FCA：3.8%，FC：4.3%）。FCA 改善高危慢性淋巴细胞白血病的无进展生存期。如预期的那样，FCA 比 FC 更具免疫抑制作用，但只要保持警惕，不会导致更高的治疗相关死亡率。该研究在 www.trialregister.nl 上注册为试验编号 NTR529。
