Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials.
Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials.
复制标题
急性髓样白血病患者中添加了gemtuzumab ozogamicin将其诱导化疗：从随机对照试验中对单个患者数据的荟萃分析。
DOI：
10.1016/s1470-2045(14)70281-5
复制
发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Burnett AK
中科院分区：
文献类型：
--
作者：
Hills RK;Castaigne S;Appelbaum FR;Delaunay J;Petersdorf S;Othus M;Estey EH;Dombret H;Chevret S;Ifrah N;Cahn JY;Récher C;Chilton L;Moorman AV;Burnett AK
吉妥珠单抗Ozogamicin（GO）是癌症中抗体导向化疗的第一个例子，并开发用于急性髓性白血病。它的作用一直不清楚。五项随机试验中，它与成人标准诱导化疗相结合，产生了不同的结果。为了阐明获益水平（如果有）以及哪些患者结局可能得到改善，对这5项试验进行了个体患者数据荟萃分析。确定了所有在成人（年龄>15岁）中进行的GO与AML（不包括APL）第一疗程强化诱导化疗联合给药的随机试验。在所涉及的组之间的合作中，于2013年5月要求提供关于人口统计学、治疗的源数据，并在3325例随机化患者（中位年龄58岁）中收集。所有试验均为集中随机化和开放标签试验，以生存期作为主要终点。通过标准技术进行分析，在标准化风险组内，缓解率没有增加，但通过显著降低复发风险，无论患者年龄如何，5年总生存率均得到改善（30.7% vs 34.6%; HR 0.90（95% CI 0.82-0.98），p=0.01）。在那些细胞遗传学良好的患者中，生存益处尤其明显（55.2% vs 76.3%; HR 0.47（0.31-0.73），p=0.0005），但也在中度风险患者中观察到（34.1% vs 39.4%; HR 0.84（0.75-0.95），p=0.007）具有不良核型的患者总体上或在任何试验中均未获益。3 mg/m2的剂量水平与较低的毒性和相等的疗效相关。GO可以安全地添加到常规诱导治疗中。对于没有不良细胞遗传学的患者，有显著的生存益处。这些数据表明，应重新评估GO的使用，并可能需要审查GO的许可证状态。本荟萃分析无资助者。
Gemtuzumab Ozogamicin (GO) was the first example of antibody directed chemotherapy in cancer and developed for Acute Myeloid Leukaemia. Its role has been unclear. Five randomised trials where it was combined with standard induction chemotherapy in adults have produced different results. In an effort to clarify the level of benefit, if any, and in which patients outcomes might be improved, an individual patient data meta-analysis of these 5 trials has been undertaken. All randomised trials of GO in adults (age >15), given in conjunction with the first course of intensive induction chemotherapy for AML (excluding APL) were identified. In a collaboration between the groups involved, source data concerning demographics, treatment was requested in May 2013 and collected in 3325 randomised patients (median age 58). All trials were centrally randomised and open-label, with survival as primary endpoint. Analyses are presented by standard techniques, and within standardised risk groups Remission rates were not increased, but by significantly reducing the risk of relapse overall survival at 5 years was improved irrespective of patient age (30.7% vs 34.6%; HR 0.90 (95% CI 0.82-0.98), p=0.01). The survival benefit was particularly clear in those with favourable cytogenetics (55.2% vs 76.3%; HR0.47 (0.31-0.73), p=0.0005), but also observed in intermediate risk patients (34.1% vs 39.4%; HR 0.84 (0.75-0.95), p=0.007) Patients with adverse karyotype did not benefit overall or within any trial. Dose levels of 3mg/m2 were associated with less toxicity and equal efficacy. GO can be safely added to conventional induction therapy. For patients who do not have adverse cytogenetics there is a significant survival benefit. These data suggest that the use of GO should be re-evaluated and the license status of GO may need to be reviewed. There was no funder for this meta-analysis.