What Important Breakthroughs Are Needed in AML Treatment? [Video]

In a roundtable discussion at the 2024 American Society of Clinical Oncology Annual Meeting, Eric Winer, MD, of the Dana-Farber Cancer Institute; Naval Daver, MD, of the University of Texas MD Anderson Cancer Center; and Yasmin Abaza, MD, of Northwestern University, shared their thoughts on what the next major breakthrough is in acute myeloid leukemia (AML) treatment.

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Dr. Winer: What do you see as the next breakthrough or global accomplishment that’s going to happen in AML in the upcoming five to 10 years?

Dr. Abaza: One of the major things that hopefully will happen in the coming years is perfecting how we use triplets with hypomethylating agents and venetoclax, and how to use more than one novel compound, like a novel-novel combination, especially once we have menin inhibitors. They’re still in trials, but if the outcomes are as good as we believe and they make it to approval, we will then talk about combining those with other novel targeted therapies.
It’s a good problem to have, having all these agents and learning how to combine and sequence them. That’s a good problem to have, and we’re going to be dealing with it in the very near future.

Dr. Daver: I think that’s absolutely true. We have a lot of tools that we can use optimally to really improve survival. There’s always a little bit of difference in where drugs get approved—showing a single agent improves complete response (CR), CR with partial hematologic recovery, and median overall survival by a few months—which is good, because you have another option. But really, we want to use these drugs to cure more patients, right?
The median survival going from five months to nine months is okay, but that’s not what our patients are looking for. Optimizing the upfront use of those drugs where we can maybe cure 10%, 20%, 30%, more like what they’re doing in multiple myeloma (MM) and other diseases. That’s one breakthrough.
The second breakthrough we really need is an effective immunotherapy. This is where we’re behind all the other hematologic malignancies—lymphoma recently, acute lymphocytic leukemia for a long time already, MM—whether it’s better antibody-drug conjugates, cellular therapies, chimeric antigen receptor T cells, or natural killer cells.
I think these are coming because a lot of the investigators and experts and the pharmaceutical industry are very cognizant that AML does not have an immune therapy. I think we will see measurable residual disease (MRD)-directed immunotherapies emerging in the future, and I think that will really push the survival up because we know we can debug, we can achieve CR, CR with incomplete count recovery in 80% to 90% to even 100% using good triplets, optimal regimens, intensive chemotherapy, whatever it may be. It’s really durability and MRD that we need to get at. In the next five to eight years, immunotherapy has to come in to really push us to the next level.

Dr. Winer: You led right into my thought, which is that the concept of MRD is extraordinarily important. As we get better at determining what true MRD is, the question then becomes who needs further therapy and who doesn’t need further therapy?
We have learned from standard MRD testing that oftentimes patients with NPM1 mutations don’t need transplant. That’s a huge step when you think about how many people, 15 years ago, we were taking to transplant without knowing MRD.
There were also patients we weren’t taking to transplant who maybe should have gone to transplant, and I think differentiating who needs to be a transplant candidate, let alone if they are a transplant candidate, is important.
If they don’t need to be a transplant candidate, we don’t need to think about that. We don’t need to think about all the things that we talked about and all the advances that we talked about in terms of what the benefits are for transplant and how great our colleagues have done, because they may not need it. That’s a very important concept that we need to try to determine for further steps and further manipulation of treatments.