The Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy in Acute Myeloid Leukaemia : An IndividualPatient Data Meta-analysis of Randomised Trials in Adults
By R. Hills, S. Castaigne, F. Appelbaum, J. Delaunay, S. Petersdorf, M. Othus, E. H. Md, H. Dombret, S. Chevret, N. Ifrah and 5 more. The Lancet Oncology, 2014
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Summary Background 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. Methods 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 Results 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. Interpretation 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. Role of funding source There was no funder for this meta-analysis.
Subfields: Hematology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/bac89a6c213075d10a84b8d4bd632b5c7a6a0de2
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Citations in the corpus
- Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. (2017, background): “An individual patient data meta-analysis of these four studies and a fifth published in abstract form reinforced these conclusions.(152) In”
- Antibody drug conjugate: the “biological missile” for targeted cancer therapy (2022, background): “Based on the overall positive outcomes achieved in above three investigator-led clinical trials, thus the Mylotarg was re-approved by the FDA in 2017.(149,151,152) Recently, a new indication of gemtuzumab ozogamicin was approved by the FDA for the treatment of newly-diagnosed CD33-positive AML to in”