ESH AL 2018 | Maintenance therapy strategies to reduce relapse in AML
Speaking from the 2018 European School of Hematology (ESH) Clinical Updates on Acute Leukemias, held in Budapest, Hungary, Charles Craddock, CBE, FRCP (UK), FRCPath, DPhil, of the University of Birmingham, Birmingham, UK, discusses novel therapies that can be given in acute myeloid leukemia (AML) post-transplant to reduce the risk of relapse.
Transcript (edited for clarity)
There’s the opportunity to deliver drugs post-transplant as maintenance therapy, that reduces the risk of disease recurrences. Two broad groups of agents that one can think of, disease-specific drugs, such as FLT2 inhibitors, and there’s promising retrospective data using sorafenib reported by the Massachusetts General Hospital, where they showed that patients who had, for whatever reason, received sorafenib post-transplant had a much lower relapse rate compared with historical controls, but a randomized prospective study is required – and that’s now launched and recruiting, looking at post-transplant gilteritinib maintenance, led by Mark Levis...
There’s the opportunity to deliver drugs post-transplant as maintenance therapy, that reduces the risk of disease recurrences. Two broad groups of agents that one can think of, disease-specific drugs, such as FLT2 inhibitors, and there’s promising retrospective data using sorafenib reported by the Massachusetts General Hospital, where they showed that patients who had, for whatever reason, received sorafenib post-transplant had a much lower relapse rate compared with historical controls, but a randomized prospective study is required – and that’s now launched and recruiting, looking at post-transplant gilteritinib maintenance, led by Mark Levis.
The other interesting observation recently reported in that setting, is that sorafenib in murine models seems to result in upregulated expression of IL-15, which accelerates donor T-cell reconstitution and may plausibly augment a graft-versus-leukemia effect. So, these putatively targeted therapies may actually be having pleotropic activities, which augment a graft-versus-tumor effect. And then the other broad group is epigenetic therapies and there’s an interesting Phase I/II data with Fand decitabine, showing not only does it upregulate a T-cell response to tumor antigens, which otherwise you normally don’t see post- transplant, but also that it’s well tolerated, and a randomized study comparing maintenance with an oral version of azacitadine, CC-486, is about to be launched.
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