Stephen Oh, MD, PhD: Similar to what you just described, Ruben, the initial prognostication when I see patients, in terms of decision-making, is largely related to the possibility or question of transplants. Of course, not every patient is eligible for transplants, but that is really the practical utility in my mind of using those prognostication schemes. The other important component, of course, is information in terms of what to expect as far as overall prognosis, and that can be, of course, very helpful for patients and their families to understand, in particular, at diagnosis. I tend not to sort of recalculate scores frequently for patients over time. I don’t find that that is particularly helpful because, again, aside from the transplant question it doesn’t really have a large impact on my recommendations for treatments. In that setting, at least with the currently available agents, the choice to start treatment is more so focused on symptoms, and in that sense, it has little bearing in terms of the risk status as to whether initiation of treatment is indicated. It’s more about their symptoms.

Ruben Mesa, MD: Jamile had mentioned that several of these newer scores certainly rely on various mutations in terms of factoring them in, which are the mutations in particular that seem to be prognostically adverse? Are you checking these panels once? Are you checking them in everyone? Are you following them? How do you use this in your practice?

Stephen Oh, MD, PhD: I think, ideally, I would obtain this kind of multi-gene panel testing in every patient with myelofibrosis that I diagnose or that I see for consultation, if they have not already had that kind of testing. And the genes in particular that I would be looking for, the so-called high-risk mutations or molecular high-risk signature, includes genes such as ASXL1, SRSF2, EZH2, IDH1 and IDH2. More recently, U2AF1 has been shown to be a higher-risk mutation. Those are the types of mutations I’m looking for.

If we’re able to obtain it, I would get it on every patient with myelofibrosis, at least initial consultation. Beyond that, or subsequently, I would not necessarily at least in terms of routine evaluation, resend that kind of testing on any particular frequency. If I am concerned that the patient may be progressing, absolutely, I would want to get it again to see if there are changes or emergence of these mutations that might not have been present before. I might also be considering the actual allele burdens to see if those are increasing over time. So those are things that I definitely would consider retesting again, if I see any hint or concern for progression. Otherwise, at this time, at least, I don’t routinely sort of screen on a yearly basis or anything like that for most of my patients with myelofibrosis. Only when, again, I’m concerned that there’s some signs of progression.

Ruben Mesa, MD: Understood. Angela, what about in your practice? In whom might you repeat the NGS [next-generation sequencing] panel? Do you do that routinely, or is there anything that you might see clinically that would suggest “boy, I better repeat this panel?”

Angela Fleischman, MD, PhD: I agree with Steve that like at the diagnosis or initial bone marrow biopsy, it is very helpful to have an NGS panel to help prognosticate. If, and again, I wouldn’t necessarily repeat a bone marrow biopsy unless there are some clinical red flags. So if there are clinical red flags, then I would like to do a sequencing panel. One, to give an explanation. If there are new mutations or something to sort of put the whole story together. If they’re clinically progressing, then maybe they’re developing a new clone, and maybe they didn’t have a high-risk mutation before and now they do. So, to put the whole picture together now, this is making sense that they really are moving in the wrong direction here.

I guess the question comes up, is in an older patient who really, from the beginning is in no way a transplant candidate, what is the role of having all of this information? That’s a good question and I always discuss it with the patient, that if they’re clearly not a transplant candidate, and to discuss with them the reality of what this new information may mean, and whether or not they think that information would be helpful for them. But clearly, if the person is a transplant candidate, and there are some red flags clinically, I think information about their mutational profile is very, very helpful in maybe sort of incentivizing a more aggressive push towards a transplant.

Ruben Mesa, MD: Very helpful. Now, Jamile, as we think about trying to determine which way we go with a patient with myelofibrosis. I tell them, there are really 3 doors, if you would. One is just observation. It’s in a minority, but it exists. Second on medical therapy, whatever that is. And third, allo [allogeneic stem cell] transplant. And obviously, all 3 of those are pretty different in terms of their intensity or impact. But in your mind, who kind of falls into each of those 3 groups at the current time?

Jamile Shammo, MD, FACP, FASCP: I think that perhaps evaluating the disease at baseline to understand [what you] are dealing with the proliferative MF and what type of constitutional symptoms that the patient has. Do they have symptomatic splenomegaly? What type of mutational analysis they have also is rather important. But to Angela’spoint, if you have someone who may be older and not a transplant candidate, a lot of comorbidities, then the goal here is to utilize a treatment that would address their symptoms and perhaps give them a better quality of life, right?

So that would be a patient that I may not necessarily be referring to transplant tomorrow. I guess you could argue could it be that maybe their symptoms are what’s driving their poor quality of life, etc. That is perhaps a subset of patients, but for the most part, it’s probably age-related. So that would be supportive care, perhaps erythropoietin to treat anemia if that’s the issue, or perhaps JAK [Janus kinase] inhibitors if the spleen is going to be an issue. We already discussed transplant. And then for those who we are watching, which I actually have a group of patients who have no symptoms, they basically had a bone marrow biopsy for mild anemia and then they have no symptoms. You simply observe and get the pace of the disease and you watch them every so often. It is something that needs to be evaluated for every patient individually.

This transcript has been edited for clarity.