A trial comparing different chemotherapy drug combinations with or without Mylotarg for acute myeloid leukaemia (AML15)

The trial team found that adding gemtuzumab ozogamicin (GO) to chemotherapy can improve treatment for many younger people without really making treatment side effects worse.

Between 2002 and 2006, the trial recruited 1,113 people to test whether adding GO improved induction treatment for AML. Their average age was 49. They were put into treatment groups at random. Neither they nor their doctor could decide which group they were in. This is called randomisation. Half the people had GO with their induction chemotherapy, the other half did not.

Between 2002 and 2009, the trial recruited 948 people who had no signs of leukaemia after induction therapy to test GO as part of their consolidation therapy. Their average age was 46. Half these people had GO with their consolidation therapy, half did not.

When comparing people who had GO and chemotherapy with people who had chemotherapy alone (either at induction or consolidation), the researchers found there was no difference in

• The number of people who had a response to treatment
• The number of people whose leukaemia came back
• The average length of time people lived (overall survival)

But by looking closely at the chromosomes in leukaemia cells (cytogenetics ), they could see that GO helped some sub groups of people more than others.

Doctors classify AML cytogenetics as being ‘favourable’, ‘intermediate’ or ‘adverse’. The analysis the researchers did in this trial showed that for people with favourable cytogenetics, there was a significant benefit in having GO with chemotherapy. For people with adverse cytogenetics, there was no benefit to having GO with chemotherapy.

By combining a number of different risk factors the researchers created a risk score, which could identify about 70% of all patients as benefiting from GO. So the trial team concluded that adding GO to chemotherapy for AML could help a lot of younger people, without causing more side effects.

The trial also compared 3 different induction chemotherapy combinations without GO. The researchers found that there was no significant difference in the average length of time people lived (overall survival) whichever combination of drugs they had. People having FLAG-Ida had fewer courses of treatment on average, while still having similar survival rates. 

In September 2013, the researchers published more results from the part of the trial comparing different types of consolidation chemotherapy.

In this part of the trial, 1,440 people were randomised to have MACE/MidAC or high dose cytarabine. People having high dose cytarabine were also randomised to have 1 of 2 different doses.

The researchers found that there was no significant difference in the number of people whose leukaemia came back or in the average length of time people lived (overall survival) between the 2 groups. There was also no difference in overall survival between people having the different doses of cytarabine.

For people with adverse cytogenetics, overall survival was better in the group who had MACE/MidAC. But people having MACE/MidAC had more side effects and spent more time in hospital.

Of the 1,779 people who completed 4 cycles of consolidation treatment, 227 were randomised either to stop treatment, or to have a 5th cycle of chemotherapy. The researchers found there was no benefit in having a 5th course.

They concluded that FLAG-Ida works well as induction treatment and that high dose cytarabine is as good as MACE/MidAC consolidation, with less time spent in hospital, except for people with adverse cytogenetics where MACE/MidAC is better treatment.

We have based this summary on information from the team who ran the trial. The information they sent us has been reviewed by independent specialists (peer reviewed ) and published in a medical journal. The figures we quote above were provided by the trial team. We have not analysed the data ourselves.