2011 ASH Annual Meeting, December 10-13, San Diego, USA
Genomic study of acute myeloid leukaemia
Professor Gail Roboz – Weill Cornell Medical College, New York, USA
At this ASH meeting I presented the education session on AML or acute myeloid leukaemia and it was a session in which the first two talks focussed on genomics in AML which has really been the major story at most major meetings in haematology/oncology for the last couple of years. So the story in AML has been less, unfortunately, novel successful therapeutics and more about genomics and identification of molecular mutations and abnormalities which characterise the disease. And actually what was presented in my session was that we may be nearing the end of the discovery phase of mutations in AML. Cytogenetically normal AML has been extensively characterised and is a very heterogeneous disease and what we’re starting to learn is how to put together the multiple mutations to come up with prognostic systems that are relevant for patients but also to come up with targeted treatment programmes that are now selecting specific subgroups of patients on the basis of their abnormalities.
So that was an interesting part of the session and then my piece was on novel therapeutic strategies. I focussed a little bit on trying to reorganise our approach to clinical trials because there has been no consistent paradigm in AML on which we’re building so that novel therapies aren’t always being added to the same type of backbone. And it makes it difficult to interpret the results. For example, the plenary session this year showed the addition of gemtuzumab ozogamicin to a reasonably standard induction and consolidation paradigm but there are two major problems. The first is that the world doesn’t do induction and consolidation the same way, so we don’t really know what the impact of the addition of the antibody will be, and secondly it’s no longer available, it was taken off the market in the United States. So that’s one of the controversies that we were discussing a little bit – that you have small movements forward in therapeutics in AML but either people don’t do things the same way so you can’t fully assess the impact or, in this case, the drug isn’t even available so it’s a little bit disconcerting to have a new standard of care in AML presented when you can’t even get the drug.
So I think the major story in AML outside of, again, further classification of mutations and how they’re going to affect prognosis and treatment strategies, is also the role of leukaemia stem cells. This is an area that’s very big at this meeting and in the last several years. That we all understand in acute myeloid leukaemia that patients go into remission but the bad guys are still there, there is residual disease that comes back for, unfortunately, the majority of patients. And the question is now that we’re understanding a little bit better the behaviour of some of the cells that are left over after chemotherapy, how to target those, how to capitalise on new data and new understanding of signalling pathways and also new understanding about the behaviour of leukemic stem cells to incorporate targeted therapies or novel therapies, both into induction and consolidation strategies, but perhaps even more importantly to incorporate them for patients already in remission where we know that the residual disease is still there but typically current treatment strategies are completely ineffective in targeting those populations.
In CML the news remains good, there are follow-up data on the TKIs suggesting that long-term durable responses are seen. There are follow-up studies on erlotinib which were presented at the meeting suggesting again that the data looked good for patients remaining in complete response. I think the issue with the TKI story in CML is… there are two major areas. Number one, there are patients who fail to respond and there is on-going drug development for agents that capture the patients who are failing to respond to the currently available ones, but also still looking at CML stem cells. So again the leukaemia stem cell story comes back and the question is with the TKIs is the disease eradicated or is it just quiescent, is it being taken down to a level that it’s no longer apparent clinically but the stem cells are still there? There are again data presented at the meeting concerning residual stem cells in CML, how they might be targeted and also where novel therapeutics might be of help there.
Take home message for ASH for patients, if you’re a CML patient you’re in good shape. If you have acute promyelocytic leukaemia, you’re in very good shape because data were presented that late relapses are extremely uncommon and actually very easily treated. If you’re an acute myeloid leukaemia patient, I still think that we have much more to do for you as a patient and although there are standard therapies that can certainly get above 50% of patients into remission, we’re still not doing a good enough job in keeping patients who attain remission in a long term remission. The message for patients is a consistent one of participation in clinical trials, it’s how you get access to a novel therapy and it’s how you get yourself away from those terrible survival curves in AML that unfortunately are still present today.