Polycythemia Vera: Prognosis and Risk for Progression to Myelofibrosis


Panel experts share insight regarding prognosis for patients with polycythemia vera and the associated risk for progression to myelofibrosis.


Pankit Vachhani, MD: The survival of patients with polycythemia vera [PV] is pretty decent compared with those with other myeloid malignancies. Nevertheless, it is slightly decreased compared with age and gender match populations from large database analyses. In one study, the median survival of patients with polycythemia vera was about 14.1 years. In another database analysis, it was about 12.4 years. Now keep in mind that the patients with polycythemia vera are diagnosed with their condition at the median age, which is in the mid- to late 60s and one may use, if they want, the MIPSS [mutation-enhanced international prognostic systems] PV risk stratification tool to estimate survival outcomes. So most survival factors that are important to note are items such as high-risk mutations and, in particular, SRSF2 mutation; a medium age of more than 67 years old; leukocytosis with a wide count of 15 or more; and also prior thrombotic history.

Aaron Gerds, MD: Patients with polycythemia vera can have a number of things happen over the course of the disease. Of course, we’re always mindful of thrombosis and progression to acute leukemias or blast phase MPN [myeloproliferative neoplasm] but some patients can progress to myelofibrosis where scar tissue builds up in the bone marrow over time, and this risk is somewhat nebulous. Some studies will say as low as 15% of patients over their lifetime will develop myelofibrosis, and some will say as high as 25%. So the truth is probably somewhere in that range.

And we’ve tried to look to identify risk factors for progression to myelofibrosis, and certainly, mutations can help predict which patients are likely to have progression. Patients with higher JAK2 allele burdens tend to have a higher risk of progression, as well as mutations that might be present in addition to the JAK2 mutation that could derive disease over time into myelofibrosis.

And other signs of that overt proliferation, such as high white blood cell counts, can also predict these things over time. But there is clearly a risk of progression in one’s lifetime with polycythemia vera for getting myelofibrosis. And there are some things that we can do to identify patients who may be at higher risk. The key next step in that story is to ask are there things that we can do to delay or reduce that risk of progression? And there is some suggestion that interferon might be able to do that, although those data are still developing.

Naveen Pemmaraju, MD: One of the emerging concepts in our field is trying to understand better the progression of disease from polycythemia vera and ET [essential thrombocythemia]. Both PV and ET are a progression to myelofibrosis, the so-called post PVMF or post ETMF. It’s very interesting. Almost always in all our clinical trials for patients, we have included all types of patients, those with de novo myelofibrosis or post PV, post ET. And now we’re trying to understand the biological basis, prognostic implications, biomarkers, and why this happens in the first place. I think when you look at PV, in particular, there is a certain percentage of patients whose disease will ultimately transform into myelofibrosis. Now that percentage varies. It’s based on certain risk factors, such as molecular mutations. We’ve learned recently that there are some higher-risk molecular mutations, maybe including splicing factor mutations, such as SRSF2 and others. And possibly there are clinical factors. We know that if you’re older than 60 years or you had a prior blood clot you have a higher chance for blood clots in general. So there are factors that we’ve seen before that can predict higher thrombotic events, progression of myelofibrosis, etc.

I think the other concept here for post-PV myelofibrosis is I believe that there’s a whole other area of research that can unfold and will over the next 5 to 10 years, trying to identify new biomarkers of progression. For example, progression of myelofibrosis to AML [acute myeloid leukemia]—we’ve uncovered that there is a series of molecular mutations that our patients will get outside of the JAK2, CALR, MPL, the 3-driver mutations. So the ASXL1 mutation, splicing factor mutations, the TP53, for example I think that’s another area that we will focus on.

And then finally, I think treatments of interest are the paradigm of treatment for the patient whose PV vs post-PV MF, myelofibrosis, has some similarities, but of course, some differences. And so, I think that’s important. And then prognostic stratification. There are scoring systems such as the MYSEC-PM, for example, that aim to specially focus on patients with post-ET and post-PV myelofibrosis. So essentially as a forward-looking situation here, I think we’re starting to understand this scenario, but I think there’s quite a bit that’s unknown, and I’m looking forward to working with all of our stakeholders around the world to better delineate this area.

Transcript edited for clarity.

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