What is maintenance therapy? What drugs are used for maintenance therapy and how effective are they at preventing relapse?

What is maintenance therapy? I think of maintenance therapy as the therapy that one gets after someone has completed their intensive chemotherapy for their acute myeloid leukemia. That is intensive induction and intensive consolidation. And maintenance is usually a low intensity treatment. By low intensity I mean a treatment that is easy to take, doesn't cause significant side effects and the purpose of maintenance therapy is to maintain the remission. That is to keep the patient from relapsing. We have one FDA approved drug for maintenance therapy in patients who have gotten intensive chemotherapy and then not had a transplant. So let's say you get your intensive induction chemotherapy and then you either get consolidation for whatever reason. There is a maintenance therapy called CC486, the trade name is ONUREG, which is an oral hypomethylating agent that patients take daily continuously, actually it is 14 days on and 14 days off. That they take and the goal of that therapy is to maintain the remission. There are other therapies that we think about using after an allogeneic stem cell transplant. So there are FLIT3 inhibitors that we often use in patients who have had a stem cell transplant with a FLIT3 mutation and after the transplant we give them FLIT3 inhibitors to maintain the remission and there are certain settings that even if you don't have a transplant we might give a FLIT3 inhibitor as a maintenance treatment. What drugs are used for maintenance therapy and how effective are they at preventing relapse? There are now some maintenance therapies that have been shown to be particularly effective in AML patients. So I think there are sort of two different settings. There are the patients that have just had chemotherapy and have not had a bone marrow transplant and in those patients there are these drugs called hypomethylating agents. One of them is called azacytidine and there's both an oral formulation of it and it can be given IV and for patients that haven't had a bone marrow transplant it has been shown that patients that get azacytidine or the oral formulation as a maintenance therapy can actually keep people in remission longer. It is a treatment that has some side effects for sure and can cause lower blood counts in particular. I think the mechanism of it is actually not that well understood and there probably is some immune modulation that happens that might explain partially why it's effective. And so that's really the primary maintenance therapy that's available for patients that haven't had a bone marrow transplant. The targeted therapies such as the FLIP3 inhibitors like mitastorin have also been used in that setting. I think there's a little bit of question, a little bit of doubt about exactly for patients that haven't had a bone marrow transplant exactly how effective they are as a maintenance therapy. They're certainly helpful in getting patients, more patients into remission initially but it's not totally clear that once you're done with the chemotherapy continuing to take that medicine is beneficial. And then there's what we do for maintenance therapy in patients that have had a bone marrow transplant and there we actually don't have any randomized controlled trials yet that show that a maintenance therapy, a targeted maintenance therapy like a FLIP3 inhibitor such as mitastorin or guilt-arritinib is beneficial. There has been a large randomized trial that has just recently finished and so we're hopeful that soon we'll know definitively an answer. Is it helpful to be on maintenance therapy after a bone marrow transplant with a targeted agent? For patients that don't have one of those targetable mutations and again it's about a third of AML patients will have a FLIP3 mutation that's targetable and 15 to 20 percent have an IDH1 or IDH2 mutation which means that about half of AML patients don't have what we would conventionally currently think of as being a targetable gene mutation. For that patient population right now there is no maintenance therapy that's been shown after a bone marrow transplant that's been shown to be beneficial. There's been a lot of interest in using those same drugs in the non-transplant setting so azacytidine in the post-transplant setting so using that after someone's had a transplant as a maintenance therapy it has not at this point in a number of randomized trials been shown to clearly be beneficial and so sometimes people still consider doing it.