Again, it's not a typical case, but say a patient was thought to be suitable for intensive induction chemotherapy and they got, say, 7 plus 3. That's one of our common regimens for AML. But then something happened during the treatment and they weren't able to get the stem cell transplant or they couldn't tolerate the consolidation. That's the ideal patient for a maintenance strategy. And actually in this Quasar AML study, this is a, not to use too much jargon, but this was a phase three, so a randomized study. One of the few randomized studies of maintenance that actually showed an overall survival benefit for patients who took the oral form of the azacytidine after receiving intensive induction, but without a stem cell transplant. So again, it's not usually our intent to give somebody intensive induction if they're not going to get a stem cell transplant, but if it happens, that's the ideal patient. Also high risk patients, again with the high risk being high risk of relapse, for those patients we would recommend the stem cell transplant after intensive induction. And even after the stem cell transplant, they still may remain at high risk. So these would be patients with TP53 mutations or complex karyotype, any of these adverse prognostic factors, flip 3 ITD mutations. Again, it hasn't been studied in the same phase three manner, but there are studies showing potential benefit to additional maintenance therapy after stem cell transplant for those high risk patients. So that could be azacytidine. There was a recent study published from MD Anderson, so it was a single center, and they were able to accumulate over many years enough patients to show that there was a slight benefit to giving the intravenous or injection azacytidine after stem cell transplant. But again, it wasn't a randomized study, and there's actually an ongoing study, international study, multi-center testing the oral form of azacytidine post-transplant maintenance. So we're all kind of waiting for that to come out. And if the poor risk factor was a flip 3 ITD mutation, mitosterin, which is a targeted agent targeting flip 3, is being studied for post-transplant maintenance or other forms of flip 3 inhibitors. So there's many of these trials. I actually encourage a lot of my patients to consider a clinical trial. Again, they have to weigh the pros or benefits for them, but in order to further the progress in this field, we need to study them in rigorous clinical trials. And so we need patients that are willing to do that, and it may actually end up benefiting them based on the early data we have. But the main point is we don't know at this point, so it's still something they need to weigh the risks and benefits for themselves. So at present, the patients who are best suited for maintenance therapy are those who are already in a complete remission and cannot move forward with a more definitive option such as allogeneic stem cell transplantation. In the post-transplant setting, where many maintenance therapies are being tested, usually in subtypes of acute leukemia that are more aggressive and they are less likely to have a cure, this is an area of exploration beyond the seraphineib which we discussed. Many, many targeted agents are being assessed in that arena, including the IDH inhibitors and the flip 3 inhibitors.
