What AML treatments in development are showing promise? Dr. Eric Winer, an AML expert and researcher, discusses emerging treatments and the importance of clinical trials, noting the shift toward more personalized, targeted therapies.   

Dr. Eric S. Winer is Assistant Professor of Medicine at Harvard Medical School and Clinical Director of Adult Leukemia at Dana-Farber Cancer Institute. Learn more about Dr. Winer.

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Transcript: 

Katherine Banwell:

What can you tell the audience about menin inhibitors for AML? 

Dr. Eric Winer:

Menin inhibitors are a very exciting, novel agent that’s come about in the next few years. The science of that actually stemmed from one of the laboratories at Dana-Farber, a physician named Scott Armstrong. Menin inhibitors are particular small molecule agents that are given orally that prevent the proliferation of leukemia cells. 

And really, initially, as of a little while ago, we thought that it was two particular mutations, something called NPM1 and something called KMT2A.  

But maybe we’re thinking that there may be other mutations that actually are also affected by these menin inhibitors. What’s important now is there are three different menin inhibitors in clinical trials in different stages that are very close to being approved, and so this is going to add just another agent in our armamentarium in order to treat AML and treat it specifically.  

I think one of the important aspects of this is that these medications, although not approved right now, are really showing a lot of clinical benefit in clinical trials. And so, it really highlights the importance of thinking about clinical trials when being treated with these diseases because the patients that are on these trials right now, and that are doing well with these medications, if they’re not in a center that has a trial, or they choose not to go on the clinical trial, then they don’t have the opportunity to have these drugs, and they don’t have the opportunity to get that improvement. 

Katherine Banwell:

Is there other research in AML that you’re excited about? 

Dr. Eric Winer:

Yeah, there is a lot of different research going on in AML constantly. One of the important aspects of AML is that we’ve changed the way we think about the disease over the past, say, 10 years or so. Ten years ago, we really only focused on a couple of different genetic mutations and focused on chromosomal abnormalities.  

What we’ve done now is we’ve been able to fine-tune things a little bit deeper, not just to look at chromosomes, but also to look at the genes that are involved. When we think 15 years ago, maybe we looked at two genes that were involved in these mutations and these mutational analyses. Now, we’re running panels that are between 50 and 90 gene mutations.  

We can determine if there is a particularly actionable gene that we can go after to gain benefit gain better responses, and gain remissions. Over these past 10 years, we’ve had a number of different drugs approved that are what we call small molecule inhibitors. There are a number of different small molecule inhibitors targeting different mutations. For example, there is a particular mutation called FLT3. There have been three drugs that have been approved over the past eight years to target that particular mutation, midostaurin (Rydapt), gilteritinib (Xospata), and quizartinib (Vanflyta).  

These actually are very specific to that mutation, and all three of them have shown significant improvement when patients are treated with those inhibitors. Similarly, there’s a mutation called IDH1 and IDH2. There have been small molecule inhibitors, ivosidenib (Tibsovo), enasidenib (Idhifa), and olutasidenib (Rezlidhia), which basically are targeting those particular mutations.  

In targeting those mutations, you’re gaining improvement. You’re gaining a better response, but more so by targeting these mutations, you oftentimes are having less side effects than what you would see with what I call old-school, conventional chemotherapy.  

The landscape of leukemia is dramatically changing right now, and it’s been dramatically under a transformation over the past, say, seven, eight years, where we went from looking at high doses of chemotherapy that was like a nuclear bomb exploding all over the marrow and wiping everything out, to really creating more of a targeted approach to how we treat patients. Almost thinking of it more as a personalized medicine in a way. 

A lot of people come in thinking about chemotherapy as the chemotherapy that their grandmother went through, or that their friend went through in the 1970s or ‘80s. And it really is a very different world. So, I think with these progressions that we’ve made, and with these advances that we’ve made, leukemia, although it still is a very frightening prospect, it’s something that we’re really making large strides in improving, and that I expect to continue to improve over the years.