Case Studies in Myeloproliferative Neoplasms - Episode 3

Case 1: Risk Assessment in P. Vera

Dr. Ruben Mesa and panel discuss the importance of and methods for risk assessment in patients with polycythemia vera.

Ruben Mesa, MD: You brought up the issue of risk and prognosis. As I like to share with folks, for us to come up with a treatment plan—and we’re getting there—we first have to be sure that we’ve made an accurate diagnosis. We’ve walked through that part. Next, I like to assess the disease burden. How is it bothering the patient? Do they have thrombosis? Do they have symptoms? Then there’s the issue of risk and prognosis. In many diseases, the issue of risk may be related to how long an individual is going to live. In PV [polycythemia vera], it can include both the issue of risk of a vascular event as well as prognosis in terms of how long an individual might live. Prithviraj, why don’t you walk us through that concept? What is risk and what is prognostic in PV?

Prithviraj Bose, MD: Absolutely, Ruben. As you pointed out, there are 2 things here. Risk for thrombosis is what really guides our management strategy. That is still fairly simple. Officially, it’s still just the age and history of a clot. Having neither of those risk factors makes you low risk. Having 1 or both makes you high risk. That said, most of us would pay attention to the white blood cell count as well because that has also been implicated in thrombotic risk in some studies. That would be as far as stratifying them for thrombotic risk. Moving over to prognosis, which is obviously not the same discussion as it is in MF [myelofibrosis], where you’re trying to decide whether somebody should be transplanted. Obviously, that’s not the question here because PV thankfully has quite a favorable survival. But the factors there have evolved as well. Age is very important, and leukocytosis uniformly seems to correlate with a worse survival. And although less frequently found, karyotypic abnormalities and, more recently, splicing mutations—SRSF2, to be to be exact—have a bearing on prognosis and potent and inferior prognosis. It’s really those things. Thrombosis history comes into that as well. There are now classifications for a model. Like for MF, we now have MIPSS-PV [Mutation-Enhanced International Prognostic Systems for PV], which incorporates these factors.

Ruben Mesa, MD: Stephen, we have this concept of risk. You’re also a molecular biologist who is doing research on the mutations that perhaps will give us further clues and help tease apart the prognosis in PV. Considering some of the recent data that Dr Brady Stein presented at ASH [American Society of Hematology Annual Meeting], we must keep in mind that not everyone who has PV does well. Overall, it’s a group that does reasonably close to survival with age-matched controls, but certainly not everybody. It’s a heterogeneous group. How does risk impact our treatment choices? Does how we manage patients impact the risk of thrombosis? Does life expectancy impact our treatment choices?

Stephen Oh, MD, PhD: That’s a really important question. As you outlined, there are different types of risk. When we talk about thrombotic risk, it absolutely impacts our treatment choices. As Prithviraj outlined, we use the traditional low risk vs high risk based on age and history of thrombosis. The recommendation to include cytoreductive therapy for those in the high-risk group has been the convention for many years. There certainly are nuances within that as to when and which agents you might use, but focusing on thrombotic risk, without question, has a significant impact on our treatment recommendations.

When you get into risk as it pertains to overall survival, that’s where it gets murkier. It is certainly being more well established that there are specific risk factors associated with inferior long-term prognosis or increased risk of transformation to myelofibrosis or to acute leukemia over time. Fortunately, in most cases, we expect patients with polycythemia vera to live for a very long time before those are going to be issues. I want to have all the available data with these patients—for instance, NGS [next-generation sequencing] testing for high-risk mutations—but the reality is that we’re not going to do a whole lot with that information for a patient with polycythemia vera in the shorter term as far as treatment. In the case of myelofibrosis, we have a much stronger justification for utilizing these kinds of extended genetic testing panels for practical use. In PV, it has a little less of an impact, in some respects in a good way, because we know that most patients are going to do well—at least for a certain period of time.

This transcript has been edited for clarity.