Expert Perspectives on Current and Emerging Therapies for AML - Episode 13

Role of Stem Cell Transplant in Acute Myeloid Leukemia

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Before closing out their discussion on first-line treatment options for patients with AML, expert oncologists reflect on the role of stem cell transplant in AML.

Transcript:
Jorge E. Cortes, MD:
Before we move to the salvage setting, Brian, we talked about transplant, and we’re not going to specifically talk about transplant, but what about some of these targeted agents in the context of post-transplant therapy? There has been a lot of interest, in the old days with azacitidine, but now more with FLT3 inhibitors, IDH inhibitors, and maybe soon, the Menin inhibitors. What do you think the role is, would we use them for everybody? Would we do it based on PCR [polymerase chain reaction]? How do you see that evolving?

Brian Andrew Jonas, MD, PhD: That’s a broad topic, so let me see if I can whittle it down to some subtypes. The one piece of data we have, I know it’s not popular, would be the SORMAIN trial, which showed an EFS [event-free survival] benefit for sorafenib maintenance after transplant. I think they got it for 2 years, if I’m remembering correctly, and that trial was not perfect. It was terminated prematurely, I think due to accrual issues. But that’s one piece of randomized evidence we have, and it illustrates the importance of maintenance post-transplant in people with FLT3 mutations in particular. I think everyone is excited about how gilteritinib is shaping up as a post-transplant maintenance agent in FLT3-mutated AML [acute myeloid leukemia] because sorafenib is not particularly easy to give, patients have a hard time tolerating it. Midostaurin after transplant also has some potential issues with toxicity. There is a BMT CTN trial with gilteritinib, a randomized trial. It will be interesting to see how that one pans out.

There is definitely excitement with some of these newer agents of the three. Of course with the quizartinib data that [Harry] Erba, [MD, PhD,] presented, there is maintenance after transplant, and that’s built into that study, so there’ll be some evidence that comes out of that. Then looking at other subsets, and I just scratched the surface on FLT3, so I’ll let my other colleagues chime in if there are additional things they want to say. But in terms of the other subsets, there seems to be some benefit potentially to using IDH inhibitors in the post-transplant setting, at least in nonrandomized small studies at this point. One area that begs for post-transplant maintenance is TP53-mutated AML. As we’ve highlighted before, this is a terrible prognosis population, even with transplant, although that still represents the best thing we have. I think doing something effective in maintenance, maybe a magrolimab-based therapy, or APR-246-based therapy, is appealing for that subset. As you pointed out, Menin inhibitors may have a role post-transplant, and there have been plenty of reports that suggest there is a role for azacitidine maintenance, as you said already, Jorge, in some patients post-transplant. I know that was a high-level view on everything, but I’d be curious to see if my colleagues can fill in any gaps I might have left out.

Jorge E. Cortes, MD: Certainly, this is work in progress, and I think they’ll find a role. We need those studies to continue and find the right setting. It’ll be interesting to continue that story.

Transcript edited for clarity.