The Use of Molecular Testing in MDS

Transcript:

Mikkael Sekeres, MD, MS: We keep circling back to molecular testing because that is, I think, the way things are going. There’s even a big discussion in 1 of the oral sessions at ASH [American Society of Hematology] about doing away with blast percentage altogether for distinguishing MDS [myelodysplastic syndrome] from leukemia. We should really be just relying on other factors like molecular testing. How do you incorporate molecular testing into your risk stratification?

Ellen K. Ritchie, MD: Certainly if there is something…. If I see what would be a low-risk MDS patient who has a p53, I put that patient in a totally different category. If they have p53-related disease, then they have a very poor prognosis. So, again, people don’t always play by the rules. Certainly, if I see 6 or 7 abnormalities that are molecular, even though if it’s a low-risk patient, I begin to worry that that patient is in a higher-risk category. If I see a simple DNMT3A or I see a TET2 as the only abnormality, that gives me some reassurance that that patient is probably not going to progress as quickly.

I do use that information in a lot of ways. I’m lucky enough that for some patients, we’re able to see progression of their molecular results. They may have come with a TET2, but when I do the next bone marrow 6 months later, they suddenly have acquired 2 more abnormalities. That’s really important, too, because it’s a dynamic way of determining that this patient may not do well. I find that it can be very helpful, and if they have a SF3B1, then I feel very reassured that that patient is going to have a more indolent course. I think it’s very helpful in that it allows us to have another tool with which to stratify patients. How this works out in the long run will be interesting as we gather more data looking at those patients who are getting while genome sequencing; seeing if we’re stratifying. If we stratify even more dramatically, are we going to be able to determine those patients who need to go to transplant right away or need a special therapy because of their genetic abnormality?

Rami Komrokji, MD: I think the importance also is that we are at the edge, or we are almost there, where we are using some of this information to tailor treatment accordingly. For patients that have a p53 mutation, we are sending them to clinical trials that look promising in those patients. For patients with SF3B1, they have certain options, too. Patients that have an IDH1 [isocitrate dehydrogenase 1] or IDH2 [isocitrate dehydrogenase 2] mutation may benefit from some treatment. We are starting to incorporate those in our decisions for management. One thing that we talked about—I think we are focusing mostly on disease-related factors. The prognosis on the outcome and risk stratification are always host-related factors.

So, we have to think of the comorbidities for the patient, their frailty. If you could look at patient numbers, they look perfect. You walk into the room and that patient cannot get from the chair to the table to be examined, and obviously we always have to keep those factors. There are several more things that try to incorporate comorbidity, frailty. There are studies that actually just look at the fatigue degree. It’s almost as predictive as IPSS [International Prognostic Scoring System] high or low in predicting the outcome for patients. We always have to keep the host-related factors, particularly if we are thinking of a transplant for the patients as well.

Jamile M. Shammo, MD: It’s so interesting because even like in the IPSS-revised, I think they thought age and performance status both mattered relative to survival but not for leukemia evolution which is they weren’t included. But they mattered, obviously. I think performance status definitely plays a big role. But back to the NGS [next-generation sequencing], the molecular sequencing, I think yes, it helps all of us for identifying targets—for prognostication, for transplant purposes. But it’s still at its infancy. Perhaps I find it more helpful therapeutically in the relapsed setting. This is because a lot of times patients may acquire certain mutations that they may not have had in the beginning that may be helpful therapeutically. So, there is more to come on that I’m sure.

Mikkael Sekeres, MD, MS: My general approach to mutations, and this isn’t perfect because we’re not at a perfect place with this either, if you’re doing a quick and dirty, I will upstage patients one category for poor-risk molecular abnormalities. That was actually shown by Rafael Bejar, MD, PhD, in a paper. For patients who had specific abnormalities—actually, Rami, you mentioned them earlier, things like p53, EZH2, ASXL1. If a patient you would have categorized as having low-risk disease, you move them up to intermediate-1. For a patient who was intermediate-1, you move up to intermediate-2. This is important for when to refer a patient to transplant for MDS. We tend to transplant patients who have higher-risk disease up front and patients who have lower-risk disease, we wait until their disease evolves. So, that does influence me nowadays to potentially refer somebody to transplantation.

Transcript Edited for Clarity