添加吉妥珠单抗奥佐米星到新诊断的急性髓系白血病诱导化疗中的效果：前瞻性随机 III 期试验的荟萃分析。
Effect of adding gemtuzumab ozogamicin to induction chemotherapy for newly diagnosed acute myeloid leukemia: a meta-analysis of prospective randomized phase III trials.
机构信息
Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing, China.
出版信息
Ann Oncol. 2014 Feb;25(2):455-61. doi: 10.1093/annonc/mdt566.
BACKGROUND
Gemtuzumab ozogamicin (GO) is a targeted antineoplastic agent comprised of a recombinant anti-CD33 humanized antibody linked to calicheamicin. Previous trials have showed conflicting results concerning the efficacy and toxicity of adding GO to induction chemotherapy for newly diagnosed acute myeloid leukemia (AML). A systematic review and meta-analysis was conducted to resolve this controversial issue.
PATIENTS AND METHODS
Summary data from five randomized phase III trials compared adding GO to induction chemotherapy with induction chemotherapy alone for newly diagnosed AML were meta-analyzed. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and relapse-free survival (RFS), and pooled odds ratios (ORs) and 95% CIs for complete remission (CR) rate, incidences of resistance disease, relapse and toxicity were calculated.
RESULTS
Data of 3596 patients (1798 GO and 1798 controls) from five randomized phase III trials were analyzed. Compared with induction chemotherapy alone, adding GO significantly prolonged OS (HR 0.93, 95% CI 0.86-1.00, P=0.05) and RFS (HR 0.87, 95% CI 0.79-0.95, P=0.003), decreased the incidences of resistant disease (OR 0.71, 95% CI 0.55-0.93, P=0.01) and relapse (OR 0.75, 95% CI 0.63-0.90, P=0.002), but had no effect on CR rate (OR 1.15, 95% CI 0.91-1.46, P=0.24). Sensitivity analysis yielded similar results. Subgroup analysis identified that cytogenetics might be an influencing factor for the effect of adding GO. In addition, the risks of grade 3-4 nausea/vomiting, diarrhea and liver aspartate transaminase (AST) elevation were increased in GO arm.
CONCLUSIONS
Adding GO to induction chemotherapy for newly diagnosed AML can significantly prolong OS and RFS, decrease incidences of resistant disease and relapse, but may increase risks of grade 3-4 nausea/vomiting, diarrhea and liver AST elevation.
背景
吉妥珠单抗奥佐米星（GO）是一种靶向抗肿瘤药物，由重组抗 CD33 人源化抗体与加利车霉素连接而成。先前的试验对新诊断的急性髓系白血病（AML）患者诱导化疗中添加 GO 的疗效和毒性存在相互矛盾的结果。进行了系统评价和荟萃分析以解决这一争议问题。
患者和方法
对五项随机 III 期试验的汇总数据进行了荟萃分析，比较了新诊断的 AML 患者诱导化疗中添加 GO 与单独诱导化疗的疗效。计算了总生存期（OS）和无复发生存期（RFS）的合并风险比（HR）和 95%置信区间（CI），完全缓解（CR）率、耐药疾病发生率、复发和毒性的合并优势比（OR）和 95%CI。
结果
对五项随机 III 期试验的 3596 例患者（GO 组 1798 例，对照组 1798 例）的数据进行了分析。与单独诱导化疗相比，添加 GO 可显著延长 OS（HR 0.93，95%CI 0.86-1.00，P=0.05）和 RFS（HR 0.87，95%CI 0.79-0.95，P=0.003），降低耐药疾病（OR 0.71，95%CI 0.55-0.93，P=0.01）和复发（OR 0.75，95%CI 0.63-0.90，P=0.002）的发生率，但对 CR 率无影响（OR 1.15，95%CI 0.91-1.46，P=0.24）。敏感性分析得出了相似的结果。亚组分析表明，细胞遗传学可能是添加 GO 效果的影响因素。此外，GO 组 3-4 级恶心/呕吐、腹泻和肝天冬氨酸转氨酶（AST）升高的风险增加。
结论
新诊断的 AML 患者诱导化疗中添加 GO 可显著延长 OS 和 RFS，降低耐药疾病和复发的发生率，但可能增加 3-4 级恶心/呕吐、腹泻和肝 AST 升高的风险。
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