What Are The Biggest Breakthroughs in AML Treatment?

Eric Winer, MD, of the Dana-Farber Cancer Institute held a roundtable discussion on acute myeloid leukemia (AML) with Navel Daver, MD, of the University of Texas MD Anderson Cancer Center, and Yasmin Abaza, MD, of Northwestern University, at the American Society of Clinical Oncology 2024 Annual Meeting in Chicago, Illinois.
This segment of the discussion focuses on the most influential developments in the treatment of AML.
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Dr. Winer: Since all of us have been doing this for some time, just to look back and reflect, in the past 10 years or so, what would you say is the biggest breakthrough in AML treatment or AML management?
Dr. Daver: I think it’s two things. It’s venetoclax and targeted therapy. If I had to say today the change in outcomes in AML, whether it’s for older patients-well, more for younger patients-but even for older patients, it’s been FLIT3 inhibitors. In younger patients, if we look at data from 2002 and 2003 with FLIT3-ITD mutated frontline patients. With intensive chemo, many groups showed 20% to 25% was the five-year survival.
Today, in the recent studies, if you look at QuANTUM-First and other data sets, we’re looking at 60% and potentially higher in the 60 years of age and younger, fit patient population. That may even get better with the use of more transplant and maintenance and molecular measurable residual disease to guide who may need maintenance and who doesn’t. I think that’s been a big step in the younger patients and in those who are older venetoclax undoubtedly has had the most impact.
We have to be careful, because even though hypomethylating agent (HMA) plus venetoclax is good, sometimes it becomes a crutch where people believe it’s better than it really is. It’s good, no doubt-we went from 8% long-term, three-year survival to 24%, but it’s not really where we want to be in the end.
It’s a good backbone, and it’s brought a lot of optimism. A lot of companies that were afraid of going in to older AML are now interested. I think we will see more and more momentum, and that’s because of the incorporation of HMA-venetoclax. Of course there are other things, maintenance, gemtuzumab, pegcrisantaspase that have contributed, but I think targeted therapies and venetoclax and the combinations of those so far have really impacted the field.
Dr. Abaza: I agree, and now the incorporation of next-generation sequencing (NGS) from a diagnostic perspective and getting NGS quickly-at our institution, we can get NGS within five to seven days. We don’t treat anymore until we have full information. I think that’s a major change from previously when everyone just got the same seven plus three, regardless of what mutations they had.
That has drastically changed in recent years, and that’s what made the development of these targeted therapies feasible. It helped us to guide therapies moving forward.
Dr. Winer: You guys brought up the top two that I was thinking about as well, which is both the targeted therapies and the way that we can better diagnose the disease. I had to come up with a third one just because I knew you two were going first.
The one thing that has made change, especially in the past 10 to 15 years, is that the supportive care we provide now is much improved.
For example, the antifungals that we have now, compared with just being able to use amphotericin when we first started out, provide a tremendous improvement. It also shows how important it is for people who have AML to be seen at a center that excels and specializes in AML, because it’s not just the AML specialists, it’s also the specialists in infectious disease, oral medicine, and dermatology.
You really need these things and that level of expertise from a total tertiary care center. That really helps enhance outcomes for the patients.
Dr. Daver: I’ll make one more point, we don’t think about it as much because we treat leukemia and we don’t do the transplant, but I think there’s been a lot of progress in transplant and outcomes. Ten or even five years ago, most people would say we won’t transplant above 65, selective 65 to 70.
Today, I think routinely 70 is kind of totally acceptable. Even 70 to 75, many are being considered, and I think a lot of that is because they have better graft-versus-host disease medicine. They have better antifungals, better antivirals, better immunosuppression. There’s a lot of progress there, which is impacting a lot of our survival curves as well. We have to give some credit to the transplant field as well.
Dr. Abaza: Especially with haploidentical transplants now.
Dr. Daver: And the use of haplo-transplants, yeah.

[@clarkbennett2312]

I have AML and am 68. Will be going in next month for a clinical trial induction, and then the transplant. Wish me luck😊

[@amira2736]

good luck!