COSTEM 2021 | Post-transplant maintenance strategies in AML

You can always do individual decision making and you can use other TKIs, midostaurin or gilteritinib for example, because they are available, they are approved in AML and other indications – gilteritinib for refractory AML, midostaurin for induction therapy – but if you look at the actual data, then they are not supporting a clear maintenance strategy at this point. For example, in the midostaurin trials that used midostaurin for actual maintenance treatment after allogeneic stem cell transplantation was published by Maziarz recently in Bone Marrow Transplantation, I think. That was a randomized trial with a comparator arm was best available therapy. And they clearly showed in the 60 patients that they included there, there was no difference in relapse-free survivor.

And we have the big study, the RATIFY trial for first line treatment, where also patients could be transplanted within this trial, but after transplant they could not receive maintenance treatment. But those patients that only received chemotherapy were eligible for a maintenance phase for one year with midostaurin. And the subgroup analysis of this study suggests that the drug may not be as potent in the maintenance phase as in the combination therapy phase upfront. So, that’s why in the US, it’s for example, not approved as a maintenance drug, the midostaurin in Europe, it is approved, but the data are potentially not, or suggest that the drug is not as very very potent in this maintenance phase.

And yeah, and for the gilteritinib that we have the data for, the relapse/refractory patients. And in this study that was published two years ago in the New England journal by Alexander Perl and they showed that there’s a clear benefit for the patients that received gilteritinib compared to chemotherapy. And some of them also underwent then transplantation in remission. But the group of patients that then was successfully transplanted and then received gilteritinib subsequently is very small and does not really allow to draw conclusions as of the potential of gilteritinib as a maintenance drug.

And there we have the MORPHO trial ongoing, which is currently- I’m not sure if they’re still recruiting or if they are in the post recruitment phase, observing their patients. I think the data will be available sometimes 2025. Yeah. And this is a clear cut maintenance study after transplant randomized placebo control. And with first-class evidence that we can expect there from this trial.

And of course there’s another inhibitor, which is quizartinib. There was a similar study as the Perl trial with gilteritinib. They also included refractory/relapsed AML patients with FLT3 ITD mutations. And also some of these patients that responded that were in the quizartinib arm were transplanted but the same, as I just said for the Perl trial, holds true for the quizartinib trial from Corte- there are two very low number of patients that can be evaluated and I think that does not allow to really conclude about the efficacy of quizartinib as a maintenance drug. And it is also seen there that the patients have real long standing cytopenia. So, that’s another issue after transplant. So, you really have to do a randomized trial when you want to draw conclusions. And so, we don’t have data for this.