ASH 2013 - New Orleans, LA, US
Gemtuzumab improves event free survival for paediatric acute myeloid leukaemia (AML)
Dr Alan Gamis - University of Missouri-Kansas City School of Medicine, USA
Acute myeloid leukaemia has seen some gradual improvement over the past several decades through intensifying traditional chemotherapy as well as by adding allogeneic transplant to the up-front therapy. We’ve also seen some improvements through better supportive care as well. However, we continue to see a very high toxic mortality during treatment, between 10% and even as high as 19% during treatment. We also see an increased risk of cardiac swelling in these children of greater than 7-8% because of their exposure to anthracyclines. In the end we still are only seeing event free survival of between 45-60% so we have a long way to go still.
The design of our trial was to take the best of the standard chemotherapy regimens and then in a randomised fashion assign half of our population to either receive gemtuzumab or not to receive gemtuzumab in addition to their standard chemotherapy. Those who were randomised to the agent received it two times, once during induction and once during intensification 2, which was the fourth of five courses of chemotherapy. Our primary objective of the trial was to see whether or not this would improve the event free survival from the time of study entry and indeed we did see that it did improve that significantly. We did not, however, see that improvement in the overall survival.
What about risk of relapse?
We did see that this benefit that equated to the event free survival improvement derived from the reduction in relapse for those patients who had entered remission. This was seen in all the risk groups, certainly this reproduced what the adults had seen in the low risk group and certainly indicates that this agent would be beneficial for that group of patients. What we did see that was somewhat unique was that because of the design of our trial that assigned all patients with high risk leukaemia to this regimen plus stem cell transplant while they were in first remission, we were in the unique opportunity to see if this would benefit those particular patients with that approach. Indeed we saw that our high risk patients also derived a benefit from gemtuzumab when combined with stem cell transplant by reducing their relapse risk quite a bit.
Are we going to see more tailored approaches to patient treatment?
Clearly AML is a very heterogeneous disease and our prior label of saying everybody with AML is the same is no longer correct. Therefore, tailoring that treatment is going to be very important. This is one important addition to the armamentarium to treat AML.
How should doctors in the real world be treating AML?
Continuing on with intensive standard chemotherapy is very important and really the first step into achieving the chance for long term survival. For now we have other agents to which we can target this therapy, target the AML. So what we hope to see is that this is the first of many targeted agents in addition to chemotherapy.
