Department of Internal Medicine, Centre of Integrated Oncology Cologne Bonn, University of Cologne, Germany.
Lancet Oncol. 2011 Dec;12(13):1204-13. doi: 10.1016/S1470-2045(11)70242-X. Epub 2011 Oct 10.
BACKGROUND: Chronic lymphocytic leukaemia (CLL) is an incurable and chronic disorder, with worsening prognosis for patients as their disease progresses. We compared the efficacy and safety of the combination of fludarabine and alemtuzumab with fludarabine monotherapy in previously treated patients with relapsed or refractory CLL. METHODS: Patients (aged ≥ 18 years) with CLL Binet stage A, B, or C or Rai stages I-IV were randomly assigned in a 1:1 ratio according to a computer-generated allocation schedule to open-label combination treatment (fludarabine 30 mg/m(2) per day and alemtuzumab 30 mg per day on days 1-3) or monotherapy (fludarabine 25 mg/m(2) on days 1-5) by use of an interactive voice response system. Both regimens were given intravenously for a maximum of six 28-day cycles. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00086580. FINDINGS: Fludarabine plus alemtuzumab (n=168) resulted in better PFS than did fludarabine monotherapy (n=167; median 23·7 months [95% CI 19·2-28·4] vs 16·5 months [12·5-21·2]; hazard ratio 0·61 [95% CI 0·47-0·80]; p=0·0003) and overall survival (median not reached vs 52·9 months [40·9-not reached]; 0·65 [0·45-0·94]; p=0·021) compared with fludarabine alone. All-cause adverse events occurred in 161 (98%) of 164 patients in the combination treatment group and 149 (90%) of 165 in the fludarabine alone group. Patients in the fludarabine plus alemtuzumab group had more cytomegalovirus events (23 [14%] vs one [<1%]) and grade 1 or 2 potentially alemtuzumab infusion-related adverse reactions (102 [62%] vs 22 [13%]). Grade 3 or 4 toxicities in the combination treatment and monotherapy groups were leucopenia (121 [74%] of 164 vs 55 [34%] of 164), lymphopenia (149 [94%] of 158 vs 53 [33%] of 161), neutropenia (93 [59%] of 157 vs 110 [68%] of 161), thrombocytopenia (18 [11%] of 164 vs 27 [17%] of 163), and anaemia (14 [9%] of 163 vs 28 [17%] of 164). The incidence of serious adverse events was higher in the combination treatment group (54 [33%] of 164 vs 41 [25%] of 165); deaths due to adverse events were similar between the two groups (ten [6%] vs 12 [7%]). INTERPRETATION: The combination of fludarabine and alemtuzumab is another treatment option for patients with previously treated CLL. FUNDING: Genzyme.
背景：慢性淋巴细胞白血病（CLL）是一种无法治愈的慢性疾病，随着疾病的进展，患者的预后会越来越差。我们比较了氟达拉滨联合阿仑单抗与氟达拉滨单药治疗复发或难治性 CLL 患者的疗效和安全性。
方法：年龄≥18 岁的 CLL Binet 分期 A、B 或 C 期或 Rai 分期 I-IV 期患者，按计算机生成的分配方案，以 1:1 的比例随机分配至开放标签联合治疗组（氟达拉滨 30mg/m²，每天一次，阿仑单抗 30mg，每天一次，第 1-3 天）或单药治疗组（氟达拉滨 25mg/m²，第 1-5 天），采用交互式语音应答系统。两种方案均连续 6 个 28 天周期静脉输注。主要终点是无进展生存期（PFS）。分析采用意向治疗。本试验在 ClinicalTrials.gov 注册，编号为 NCT00086580。
结果：氟达拉滨联合阿仑单抗（n=168）与氟达拉滨单药治疗（n=167）相比，PFS 更好（中位数 23.7 个月[95%CI 19.2-28.4]比 16.5 个月[12.5-21.2]；风险比 0.61[95%CI 0.47-0.80]；p=0.0003）和总生存期（未达到中位生存期比 52.9 个月[40.9-未达到]；0.65[0.45-0.94]；p=0.021）。与氟达拉滨单药治疗相比，联合治疗组 164 例患者中有 161 例（98%）和氟达拉滨单药组 165 例患者中有 149 例（90%）发生全因不良事件。氟达拉滨联合阿仑单抗组发生更严重的巨细胞病毒事件（23 例[14%]比 1 例[＜1%]）和 1 级或 2 级潜在阿仑单抗输注相关不良反应（102 例[62%]比 22 例[13%]）。联合治疗组和单药治疗组的 3 级或 4 级毒性分别为白细胞减少（121 例[74%]比 55 例[34%]）、淋巴细胞减少（149 例[94%]比 53 例[33%]）、中性粒细胞减少（93 例[59%]比 110 例[68%]）、血小板减少（18 例[11%]比 27 例[17%]）和贫血（14 例[9%]比 28 例[17%]）。联合治疗组严重不良事件发生率较高（54 例[33%]比 41 例[25%]）；两组因不良事件导致的死亡人数相似（10 例[6%]比 12 例[7%]）。
结论：氟达拉滨联合阿仑单抗是治疗既往治疗的 CLL 患者的另一种治疗选择。
资金来源：健赞公司。
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