When envisioning the future treatment paradigms for myelodysplastic syndromes and acute myeloid leukemia, researchers predict that hypomethylating agents, immunotherapies, and multikinase and BCL-2 inhibitors are just a few examples of what the field can expect in the coming years.
Guillermo Garcia-Manero, MD
When envisioning the future treatment paradigms for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), researchers predict that hypomethylating agents, immunotherapies, and multikinase and BCL-2 inhibitors are just a few examples of what the field can expect in the coming years.
Guillermo Garcia-Manero, MD, lectured on current and likely future treatment strategies in MDS and AML during the 2016 OncLive State of the Science Summit on Treatment of Hematologic Malignancies.
“I’m excited to be here and there is a lot of progress that is happening in both MDS and AML,” explains Garcia-Manero. “Over the next few years, we are actually going to start making a major impact on the lives and outcomes of our patients. [I focused on] where the research is going, what are the most important clinical trials that we have for our patients, and some other interventions that are quite innovative for the care of patients with MDS and AML.”
In an interview with OncLive, Garcia-Manero, MD, professor of Medicine, chief, Section of Myelodysplastic Syndromes, in the Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discussed classification of MDS and AML, ongoing trials with the potential to impact management of these diseases, and ensuring research and treatment breakthroughs are translated to community practice.Garcia-Manero: I discussed how we classify patients with myelodysplastic syndromes and not from typical standard classifications, but from more functional type of models. We talked about this concept of potential prevention strategies for patients with therapy-related myeloid leukemia. There is a discovery where we can, in a way, predict who may or may not be at risk for developing leukemia after being treated for a solid tumor. This is a major discovery that I think is going to have quite a bit of implication for the future.
I went through different therapeutic strategies for patients with low-risk MDS and high-risk MDS. Particularly, we are very interested in these patients who have failed on a hypomethylating agent. This is a difficult subset of patients. They have a different natural history, and we’re trying to develop new treatments for these patients.
What are the ongoing clinical trials in this space?
What are some of the main challenges in MDS that you would like to see addressed?
There are also drugs that I see in common with MDS and AML. As I mentioned earlier, the use of BCL-2 inhibitors is going to be very important in combinations with second-generation hypomethylating agents, such as SGI-110 (guadecitabine) or CC-486 (oral azacitidine).First of all, we are talking about 2 different diseases—myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). I focused more on MDS because it’s my primary area of interest. We divide this disease into low-risk and high-risk categories, and then we have a number of clinical trials for both patients who present with either high- or low-risk de novo, and patients who have actually been treated with these hypomethylating agents.The main challenge is that, of course, it’s not a rare disease but it’s not the most common disease either. We have learned over the years that the disease at the molecular level is highly heterogeneous. The challenge is going to be how to basically get new drugs approved for small subsets of patients. The FDA is starting to think about treatments as not just for MDS in general, now that we are going into the times of targeted interventions and these types of approaches. What types of guidelines do we need to approve new compounds for our patients? The traditional dogma of a big survival-based randomized trial is not possible for some of these particular groups of patients.
In the next 5 to 10 years, what do you see on the horizon?
That’s very optimistic.
Therefore, we are going to have to think about innovative designs and ways that convince, not the administration, but the public, that whatever drug we have is safe and effective, and it can be used in our patients in the best possible way. People are thinking about this. Let’s say you have a very particular mutation that happens in 1% or 2% of the patients with this disease. However, the drug was very effective, and you’re not talking about a very common disease—not 1% of lung cancer or breast cancer. How do we get a drug like this approved when you can help that particular group of patients? That will be the main challenge for us.I think we’re going to cure most patients with this disease.What is going to happen over the next decade is that we put a lot of effort in understanding the different subsets of these patients. Then, people will say, “Why do we do this kind of analysis?” Well, now we understand that there are multiple different groups of patients. Now, we are starting to have the drugs that can affect the outcomes of those particular patients. Particularly with MDS, we would think about 1 disease and now probably we’re talking about 20 different entities. We would have a drug for each one, and I think we’re going to get there. By dividing and conquering, we will achieve this.
Maybe I was optimistic in saying we’re going to cure it, but I’m pretty sure that we’re going to start making or giving the opportunity to our patients to live significantly longer. We are lucky at The University of Texas MD Anderson Cancer Center that we have so many drugs and so many clinical trials, that you see patients living significantly longer than is expected or what studies show.
What do you hope that community oncologists will take away from your presentation today?
Why I’m having a problem translating this into the community is because not everybody can come to MD Anderson or to whatever the big hospital is in their community. That is what I like to see: how we translate to the public. Because a lot of these drugs are already on clinical trials, we are seeing some improvements in terms of outcomes in our patients. We are going to get there and it’s going to be by understanding that there’s more subsets, the benefits from this intervention, and so forth.At some point, I would think that most of these patients probably need to be referred to a center at least once where they can give you the right diagnosis, where they can have access to some type of molecular diagnostic tool that can really tell you, “OK, this is exactly what the patient has, this is the mutation that the patient has, etcetera.” Then, maybe you work with the community oncologist or hematologist, because if you are from 200 miles from Houston, it’s going to be difficult for you to be coming down here. I understand that.
However, we need to use our tools to really communicate from centers that see these kinds of patients back into the small communities where these people can be treated, but it’s a challenge. This is just going to get worse because the knowledge just keeps being larger and larger.
Now, we are using a lot of immune checkpoint inhibitors in our practice. This is a total new set of toxicities for me that I’m not familiar with, and you learn—but you learn with humans. You’re not a medical student anymore, so it’s challenging.
For these not-as-common entities, I suggest that patients seek a second opinion and have a true diagnostic approach.