That was the key question posed by Gail Roboz during her improvised talk at the recent Greenspan Chemotherapy Foundation meeting in New York. She was standing in for Janice Gabrilove who was unfortunately sick, but managed to put together 16 mins of incredible thoughts for where things could head next in the near future with this disease.
The ideas Dr Roboz expressed gave me a lot of food for thought, so I thought I would try and summarise a brief synopsis. If you want to hear the presentation and see the slides yourself, I would highly recommend checking out the Chemotherapy Foundation website in the link above.
If we take a look at the response rates in younger AML patients, we see some very high complete responses (CR) or remissions in the 70-80% range, yet 5 year survival is only in the 30% range:
A similar trend exists in the elderly AML group, although the corresponding numbers are a dispiriting 40-50% and 10-20% for complete response and 5 year overall survival respectively.
The answer, according to Dr Roboz, lies in understanding the role of the leukemia stem cells, which are largely quiescent and not killed by conventional chemotherapy. They persist after treatment and probably most likely to be responsible for or involved in relapse.
Currently, there are no standard post remission therapies in AML. Options include chemotherapy consolidation and allogeneic stem cell transplantation (SCT). However, what is surprising is that minimal residual disease (MRD) evaluation and maintenance strategies showing a survival benefit are standard in ALL, but not AML.
Given the poor results seen with maintenance chemotherapy in AML, Dr Roboz suggested it was time for a change in approach. She noted that many targeted drugs with good science but do not work alone in active AML could be considered for maintenance therapies in CR, via clinical trials to determine their effectiveness. These agents include the following:
In conclusion, her recommendations to try new ideas and novel approaches to the treatment of AML looks at ways of keeping the patients who achieve a complete response in remission for longer, thereby impacting the overall survival. The suggestions for personalised treatment of AML included the following:
Given that this was an impromptu presentation at very short notice, it was very well thought through and delivered. In fact, I would go so far as to say it was the one presentation that had the most vivid impact on me from the meeting, and there were many good ones over the course of four days.
Sometimes, we learn more and perhaps can see a better vision or approach when when someone articulates the issues and focuses on some new areas for consideration. I wish more researchers thought strategically like this!
I'm looking forward to seeing some Pharma companies consider the idea of targeted therapies taken as maintenance therapies in patient with AML who have achieved complete remission. If we can impact the 5 year survival rate for the better, that would be a wonderful thing indeed.