Loke J, Khan J N, Wilson J S, Craddock C, Wheatley K
Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK.
Ann Hematol. 2015 Mar;94(3):361-73. doi: 10.1007/s00277-014-2218-6. Epub 2014 Oct 5.
Conventional chemotherapy is ineffective in the majority of patients with acute myeloid leukaemia (AML), and monoclonal antibodies recognising CD33 expressed on myeloid progenitors (e.g. gemtuzumab ozogamicin (GO)) have been reported to improve outcome in patients with AML. Reports of excess toxicity have resulted in GO's licence being withdrawn. As a result, the role of these agents remains unclear. A systematic review and meta-analysis included studies of patients with AML who had entered a randomised control trial (RCT), where one arm included anti-CD33 antibody therapy. Fixed effect meta-analysis was used, involving calculation of observed minus expected number of events, and variance for each endpoint in each trial, with the overall treatment effect expressed as Peto's odds ratio with 95 % confidence interval. Meta-analysis of 11 RCTs with 13 randomisations involving GO was undertaken. Although GO increased induction deaths (p = 0.02), it led to a reduction in resistant disease (p = 0.0009); hence, there was no improvement in complete remission. Whilst GO improved relapse-free survival (hazard ratio (HR) = 0.90, 95 % confidence interval (CI) = 0.84-0.98, p = 0.01), there was no overall benefit of GO in overall survival (OS) (HR = 0.96, 95 % CI = 0.90-1.02, p = 0.2). GO improved OS in patients with favourable cytogenetics, with no evidence of benefit in patients with intermediate or adverse cytogenetics (test for heterogeneity between subtotals p = 0.01). GO has a potent clinically detectable anti-leukaemic effect. Further trials to investigate its optimum delivery and identification of patient populations who may benefit are needed.
传统化疗对大多数急性髓系白血病（AML）患者无效，据报道，识别髓系祖细胞上表达的CD33的单克隆抗体（如吉妥珠单抗奥唑米星（GO））可改善AML患者的预后。关于毒性过大的报道导致GO的许可被撤回。因此，这些药物的作用仍不明确。一项系统评价和荟萃分析纳入了参加随机对照试验（RCT）的AML患者的研究，其中一组接受抗CD33抗体治疗。采用固定效应荟萃分析，计算观察到的事件数减去预期事件数，以及每个试验中每个终点的方差，总体治疗效果以Peto比值比及其95%置信区间表示。对11项RCT进行了荟萃分析，其中13次随机分组涉及GO。虽然GO增加了诱导死亡（p = 0.02），但它导致耐药疾病减少（p = 0.0009）；因此，完全缓解率没有提高。虽然GO改善了无复发生存期（风险比（HR）= 0.90，95%置信区间（CI）= 0.84 - 0.98，p = 0.01），但GO对总生存期（OS）没有总体益处（HR = 0.96，95% CI = 0.90 - 1.02，p = 0.2）。GO改善了细胞遗传学良好的患者的OS，没有证据表明对细胞遗传学中等或不良的患者有益（亚组间异质性检验p = 0.01）。GO具有强大的临床可检测的抗白血病作用。需要进一步的试验来研究其最佳给药方式，并确定可能受益的患者群体。
