ASH 2024 | Strategies to optimize maintenance therapy for patients with AML

So in terms of maintenance strategy, since the oral azacitidine has come on board, becoming standard of care in many countries, there has been a lot of momentum to try to look at maintenance strategies in AML. Broadly speaking, I think of them in two sort of contexts. One is for those who are not fit for an allogeneic stem cell transplant, and then obviously there is the post-transplant maintenance strategy which is a totally different kettle of fish. Focusing on those patients who have had intensive chemotherapy and then looking at a potential maintenance option because they’re not going to go for a stem cell transplant, as mentioned oral azacitidine is the current standard of care. But we know that although that did improve survival for a subset of patients, long-term outcomes are still not fantastic. So a lot of work is being done right now to look at possible maintenance strategies. I think there are two big arms in terms of how we optimize maintenance strategies. Firstly, obviously, is the efficacy. Obviously, it has to be efficacious and often we look at targetable therapies like FLT3 inhibitors, potentially menin inhibitors, potentially IDH inhibitors. Although I must say that data right now don’t seem to give us a lot of clarity around whether they actually work or not, so I think that’s something that as a whole field we need to work on: is it worthwhile putting patients on these therapies long term, is it efficacious, is it cost-effective? And I think a lot of work is looking at whether we can add drug x or y or z like venetoclax on the oral azacitidine or any other brand new combinations. One of the things that we are doing in Australia and New Zealand is we are looking at adding a dendritic cell vaccine, a vididencel onto oral azacitidine as a randomized comparison. That’s part of our again our ALLG AMLM22 study and we’re looking at that really closely. We also have a venetoclax maintenance trial that we are conducting right now again to look at is it worthwhile doing a venetoclax-based maintenance strategy. Another important aspect of maintenance is toxicity because these patients are in remission. You want them to have a good quality of life, so I think these studies really need to look at patient-reported outcomes, quality of life data, the toxicities in terms of adverse events, because even low-grade adverse events can impact on patients quite significantly. If someone’s having diarrhea, going to the toilet 20 times a day, even though it’s low grade, it could significantly impact on their life and their quality of life as well. The cost-effectiveness has to be taken into account because ultimately we want these drugs to be applicable to people around the globe and not just in countries who can afford these high-cost medications. So I think overall, I think maintenance strategies are the way to go, but we just need more robust data to show that it works, it works well, it is safe, and that it really benefits patients longer term and that it doesn’t actually cause evolution of new leukemia coming through. I think that’s one of the concerns or curiosity that we have is if we keep giving people drugs, are we causing clonal selection or clonal adaptation over time? That question has not been answered, so that will be an interesting aspect to explore especially with these studies now all ongoing.

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