ESH AL 2018 | Targeted vs. broader agents for maintenance in AML

Charles Craddock

Charles Craddock, CBE, FRCP (UK), FRCPath, DPhil, of the University of Birmingham, Birmingham, UK, discusses the use of targeted vs. broader agents in acute myeloid leukemia (AML). This interview was recorded at the 2018 European School of Hematology (ESH) Clinical Updates on Acute Leukemias, held in Budapest, Hungary.

Transcript (edited for clarity):

Speaking to the question of whether you should use targeted therapies or agents with broader anti-leukemic specificity, of course, is actually what do we know about the biology of disease relapse? Well, there’s some emerging data. Firstly, we’re now getting better at identifying risk factors for early relapse, so patients with the FLT3 mutation have a much higher risk of early than late relapse. There are a number of transplant factors that seem to protect against early relapse, with the choice of the use of an unrelated donor. And secondly, next-generation sequencing data, which shows that quite commonly at relapse there is loss of mutations, putative driver mutations, that were present at diagnosis, and again that steers you a little bit more towards using, as a maintenance strategy, drugs with a broader anti-leukemic specificity. And then finally, I think in this setting of maintenance we need to be thoughtful about the use of donor lymphocytes, the challenge with AML is if it relapses it relaxes quickly and to get DLI in the first 6 months post-transplant is challenging so there’s a meaningful dose. And also there’s emerging interest now of course about using CAR T-cells post-transplant and that’s an area I’m sure there’s gonna be a lot of research in.

So, broadly there’s a number of options, there’s very little randomized data to inform our practice, and what is vital and encouraging to see now is the growth of prospective randomized trials answering many of these pivotal questions, without which we’re unlikely to be able to significantly improve the outcomes after an allograft, but with which I think we’re going to firstly have a better understanding about the biology of relapse, because prospective trials drive collection of high-quality biological material, and secondly there’s every reason to believe that there are strategies out there that are going to have the potential to improve outcome.

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