Gemtuzumab Ozogamicin Boosts AML Overall Survival

Rejected immunoconjugate improves overall survival in acute myeloid leukaemia patients

medwireNews: Gemtuzumab ozogamicin, when given alongside intensive induction chemotherapy, has significant benefits for patients with acute myeloid leukaemia (AML), indicate the results of a meta-analysis.

Pooled findings from five randomised, open-label clinical trials with 3,325 patients aged 15 years or older showed that those given gemtuzumab ozogamicin plus chemotherapy were significantly less likely to experience disease relapse than those receiving chemotherapy alone (odds ratio [OR]=0.81) and consequently had significantly better 5-year overall survival (OR=0.90).

However, the immunoconjugate drug targeting the myeloid cell Receptor CD33 did not significantly increase the rate of complete remission or peripheral count recovery compared with chemotherapy alone.

Gemtuzumab ozogamicin was rejected by the European Medicines Agency in 2008 and then withdrawn from the US market in 2010 due to an increased risk of patient death.

Alan Burnett, from Cardiff University in the UK, and co-authors write in The Lancet Oncology that their data “provide strong evidence that consideration should be given to revision of its regulatory status with a view to making it available to patients.”

After 6 years of follow-up, patients with favourable cytogenetic characteristics, as assessed by the UK Medical Research Council classification, had a particularly high absolute survival benefit from gemtuzumab ozogamicin (20.7%, OR=0.47), with a smaller benefit found for patients with intermediate characteristics (5.7%, OR=0.84).

By contrast, patients with adverse cytogenetic characteristics derived no significant survival benefit from treatment with gemtuzumab ozogamicin (2.2%, OR=0.99), prompting the researchers to recommend that AML patients be assessed for cytogenetic features and treated accordingly.

The meta-analysis also indicated that patients given gemtuzumab ozogamicin at a 3 mg/m2 dose had a significantly lower 30-day mortality rate than those treated with 6 mg/m2 and that a fractionated schedule of treatment might be associated with a reduced risk of relapse compared with non-fractionated regimens.

In an accompanying comment, Mohamed Kharfan-Dabaja, from University of South Florida College of Medicine in Tampa, USA, says that while optimum dose and schedule “remain elusive,” a single 3 g/m2 dose or a fractionated regimen would be “reasonable recommendations for prescribing guidance” on use.

“The overall survival benefit in favourable-risk and intermediate-risk acute myeloid leukaemia is significant, and should not be ignored”, concludes Mohamed Kharfan-Dabaja, supporting a call to regulatory authorities to make the agent available again.


Hills R, Castaigne S, Appelbaum F, et al. 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.Lancet Oncol 2014; Early Online Publication 7 July. doi:10.1016/S1470-2045(14)70281-5

Kharfan-Dabaja M. A new danw for gemtuzumab ozogamicin? Lancet Oncol 2014; Early Online Publication 7 July. doi:10.1016/S1470-2045(14)70289-X

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