Effect of adding gemtuzumab ozogamicin to induction chemotherapy for newly diagnosed acute myeloid leukemia: a meta-analysis of prospective randomized phase III trials

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.

Keywords: acute myeloid leukemia; gemtuzumab ozogamicin; induction chemotherapy; meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aminoglycosides / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Gemtuzumab
  • Humans
  • Induction Chemotherapy
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Proportional Hazards Models
  • Treatment Outcome


  • Aminoglycosides
  • Antibodies, Monoclonal, Humanized
  • Gemtuzumab