Gemtuzumab has never been approved in the EU; the CHMP refused marketing authorisation in 2008 due to insufficient evidence to establish its effectiveness in the treatment of acute myeloid leukaemia (AML). It was intended for use as a re-induction treatment of patients with CD33-positive AML in first relapse who are not candidates for other intensive re-induction chemotherapy regimens.
It was approved for use in the US, but later withdrawn after results of a study conducted to justify its original accelerated approval. This study was terminated early because of a significant excess of early mortality in the group given gentamicin. The authors of the meta-analysis comment however that early mortality was exceptionally low in the control group of this study, and the mortality associated with gemtuzumab was similar to what would be expected from conventional treatments. They therefore consider the question of whether gemtuzumab provides an overall benefit with acceptable early mortality to remain unanswered.
The results of this meta-analysis of individual patient data from 5 RCTs suggest that the addition of gemtuzumab to standard induction chemotherapy for AML did not improve remission rates, but reduced the risk of relapse and improved overall survival in patients with favourable-risk of intermediate-risk cytogenetic characteristics. The studies analysed used different doses and schedules of gemtuzumab so the optimum remains unknown; the results do however suggest that 3mg/m2 provides a similar survival benefit to that seen with 6mg/m2, while avoiding excessive early mortality. Further research is required on fractionated schedules, and whether this provides significant advantages over a single dose given on day 1.
The researchers and the authors of a related Comment article say that the findings of this research support consideration of the revision of its regulatory status.