Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy Improves Survival in Older Patients With Acute Myeloid Leukemia
Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy Improves Survival in Older Patients With Acute Myeloid Leukemia
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DOI：
10.1200/jco.2012.42.2964
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发表时间：
2012-11-10
影响因子：
45.3
通讯作者：
Milligan, Donald
中科院分区：
文献类型：
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作者：
Burnett, Alan K.;Russell, Nigel H.;Milligan, Donald
目的在过去的二十年中，老年急性髓系白血病(AML)患者的生存期几乎没有改善。改善诱导治疗可提高缓解率和缓解率，从而提高存活率。在我们之前的试验中，在较年轻的患者中，我们发现在诱导化疗中加入健择单抗(GO)可以提高大多数患者的生存率。患者和方法未治疗的AML或高危骨髓增生异常综合征患者(中位年龄67岁，范围51至84岁)被随机分配到接受诱导化疗的患者中，在第一个疗程的第一天，接受柔红霉素/阿糖胞苷或柔红霉素/氯法拉滨的诱导化疗，有(n=559)或没有(n=556)gO 3 mg/m(2)。结果总有效率为69%，其中完全缓解(CR)60%，CR伴不完全恢复(CRI)9%，GO组(70%)与未GO组(68%)无差异。30天或60天的死亡率没有差别，GO的毒性也没有显著增加。中位随访30个月(5.5~54.6个月)，GO组3年累积复发率显著降低(68%比76%；危险比0.78；95%CI，0.66~0.93；P=0.007)，3年生存率显著提高(25%比20%；HR，0.87；95%CI，0.76~1.00；P=0.05)。这一好处在不同的小组中都很明显。没有与其他治疗干预措施相互作用。对英国国家癌症研究所两个试验中的2228名患者进行的荟萃分析表明，在复发(HR，0.82；95%CI，0.72至0.93；P=.002)和OS(HR，0.88；95%CI，0.79至0.98；P=.02)方面有显著改善。结论在诱导化疗中加入GO(3 mg/m(2))可降低复发风险，提高存活率，且毒性几乎没有增加。J Clin Oncol30：3924-3931。(C)2012年美国临床肿瘤学会
PurposeThere has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved survival for the majority of patients when adding gemtuzumab ozogamicin (GO) to induction chemotherapy.Patients and MethodsUntreated patients with AML or high-risk myelodysplastic syndrome (median age, 67 years; range, 51 to 84 years) were randomly assigned to receive induction chemotherapy with either daunorubicin/ara-C or daunorubicin/clofarabine, with (n = 559) or without (n = 556) GO 3 mg/m(2) on day 1 of course one of therapy. The primary end point was overall survival (OS).ResultsThe overall response rate was 69% (complete remission [CR], 60%; CR with incomplete recovery [CRi], 9%), with no difference between GO (70%) and no GO (68%) arms. There was no difference in 30- or 60-day mortality and no major increase in toxicity with GO. With median follow-up of 30 months (range, 5.5 to 54.6 months), 3-year cumulative incidence of relapse was significantly lower with GO (68% v 76%; hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .007), and 3-year survival was significantly better (25% v 20%; HR, 0.87; 95% CI, 0.76 to 1.00; P = .05). The benefit was apparent across subgroups. There was no interaction with other treatment interventions. A meta-analysis of 2,228 patients in two United Kingdom National Cancer Research Institute trials showed significant improvements in relapse (HR, 0.82; 95% CI, 0.72 to 0.93; P = .002) and OS (HR, 0.88; 95% CI, 0.79 to 0.98; P = .02).ConclusionAdding GO (3 mg/m(2)) to induction chemotherapy reduces relapse risk and improves survival with little increase in toxicity. J Clin Oncol 30:3924-3931. (C) 2012 by American Society of Clinical Oncology