SOHO 2021 | Why maintenance therapy in AML is unnecessary

I guess I would start out by saying that I don’t feel that maintenance therapy is not necessary. And my assignment in the debate was to argue, I think really against the generalized widespread use of maintenance therapy. So I’ll make the disclaimer that I think it has a role, although right now it’s a limited role. Part of the problem with maintenance therapy is that we’re still a little bit in the dark as to exactly how it is driving potential benefit. I think we have a poor understanding of the effect of maintenance therapy on overall clonal burden, which can potentially increase the duration of therapy to something that’s very long-term for patients receiving it.

I think that we need to recognize that maintenance therapy is not without risks or side effects. And considering the fact that remissions are generally short lived in AML, that it’s quite possible, if not probable, that the duration of maintenance therapy may approach the duration of the remission itself, potentially impacting quality of life for patients who are in remission by being on a chronic therapy. So we have a lot to learn about how to fine tune maintenance therapy to the point where we understand when it’s necessary and when it can be stopped. I think to that point, we also have really a lack of information as to how well it pertains to patients who achieved an MRD negative state. Some of the studies that I have referred to in my talk suggests that the MRD negative patients may not benefit as much from maintenance therapy, which kind of makes sense. And whether newer therapies that are intended to induce MRD negativity might somehow abrogate the need for maintenance therapy.

Another important consideration I think is that there really have been fairly few randomized studies that have truly addressed the question of maintenance therapy and only one truly positive study. And that being the QUAZAR 001 study that demonstrated the utility of oral azacitidine as maintenance therapy. But keeping in mind that the overall population of patients that was treated on that trial may not be representative of the overall AML population in general.

So I think that in its current state, maintenance therapy still has a minimal impact on AML as a whole. I believe that there’s movement in the right direction. And we have a better understanding about the importance of various clones in the propagation of relapse, and that we may be able to target our therapy more precisely. We have a better understanding of MRD. We have the ability to target MRD in a more sensitive level. So I think that maintenance therapy will evolve, but at this point in time, I don’t believe that it benefits or it has a major impact on the disease as a whole. And that’s really the point of my debate argument.