Myeloproliferative Neoplasms - Episode 3

What to Know About Polycythemia Vera and Treatment Options

Angela Fleischman, MD, PhD, and Stephen Oh, MD, PhD, discuss polycythemia vera (PV) and the possible therapies that can be used to treat patients.

Ruben Mesa, MD: Pivoting back with earlier disease, Angela, why don’t you walk us through the diagnosis and kind of initial assessment of polycythemia vera [PV]?

Angela Fleischman, MD, PhD: Many times, someone or a hematologist will be referred somebody for an evaluation of erythrocytosis and elevated hemoglobin hematocrit. In my practice that’s probably the most common referral that I get. The first thing to decide is whether this is primary polycythemia vera or secondary. Does the person have a reason that they would have a secondary erythrocytosis? First, check EPO [erythropoietin] and ask the patient do they smoke, or do they have sleep apnea? Do they take testosterone? Honestly, probably these days with JAK2 [Janus kinase 2] V617F testing being widely available, that probably is the first step. It probably is ordered at the same time as an EPO level probably before the person even sees the patient, just order the JAK2 V617F.

Many times, PV patients will have elevated white count and platelets as well. The vast majority of PV patients do have a JAK2 V617F mutation. A small fraction has a JAK2 exon 12 mutation. So if a patient is labeled as PV patient yet does not have any JAK2 mutation that may be a little bit of a dubious diagnosis there because the vast majority will have a JAK2 mutation for diagnosis and it is helpful to have a bone marrow biopsy. It is important to help determine whether the person truly has PV or may have some fibrosis in their marrow. It is also important to measure spleen size, those sorts of things.

Ruben Mesa, MD: Very helpful. Stephen, why don’t you walk us through the treatment options with PV, first in whom are you going to treat and how are you going to manage them?

Stephen Oh, MD, PhD: Sure. I think in terms of treatment thinking about what [are] the goals of treatment. There are several that can be considered or prioritized in different ways. I think classically the primary goal of treatment has been to reduce risk of thrombosis. To do so for patients with PV, generally the focus has been to reduce the hematocrit to below 45 and that target was validated by the CYTO-PV study, conducted in Italy, as confirming that that number is really the threshold that we should be aiming to achieve, keeping the hematocrit below 45. That doesn’t establish or determine the specific method of treatment to achieve that so there are a variety of approaches that can [be] and are considered, including simply phlebotomy to reduce that hematocrit and keep it below 45. However, frequency is necessary. Then, for certain patients, cytoreductive therapy, such as hydroxyurea, and in certain patients, pegylated interferon or the recently approved ropeginterferon.

The choice of those specific treatments is based on a number of factors, classically primarily based on 2 factors: age greater than 60 and or a history of a thrombosis. For those patients, generally speaking, cytoreductive therapies, such as hydroxyurea, would be considered an acceptable approach. With increasing I think use and enthusiasm of interferon, that I think brings another option to the table and not necessarily just for patients who are considered high-risk as already discussed a bit and particularly younger patients who are of childbearing age. Then also it points to another goal of therapy which is, ideally, to not just keep the hematocrit below 45 but establish a true remission, potentially a molecular response and interferon is a drug that has shown some capacity to do that.

I think for that reason there has been a resurgence of interest in interferon and again with ropeginterferon just recently being approved for PV. It gives us another option with an even longer acting form of interferon. I’ll just make sure not to forget to mention that as a backbone, unless there’s a contraindication, all patients with PV should be treated with aspirin. So aspirin for every patient unless there’s a contraindication and some method of keeping the hematocrit below 45 with the additional considerations that I mentioned.

Ruben Mesa, MD: I have to share that I was quite excited to see the approval of ropeginterferon. The interferons as a class is something that we have been studying as a field now for many years. There are really legends in our field like Dick Silver [MD, Myeloproliferative Neoplasms (MPN) Center] and Harriet Gilbert, MD [President and Director of the MPD Research Center], great colleagues from Europe like Jean-Jacques Kiladjian [MD, PhD] or Hans Hasselbalch [MD], that have been strong advocates for interferon. Indeed, particularly in PV that Dr Silver continued to update their experience from Weill Cornell Medicine showing that it may really have an impact on the disease for the long term. So, a new therapy, its indication is fairly broad.

For those that have not had a chance to use interferons, this is a little different experience than those that just used interferon in the distant past. I’m mindful. I interacted with many oncologists that they have bad memories of using high-dose interferon for chronic myeloid leukemia or even for solid tumors, really high doses lots of toxicity. This is something completely different. This is very low-dose, very long acting. There can be side effects. You need to monitor for liver function, test depression, but it’s a dramatically different story. It can really have an impact.

This transcript has been edited for clarity.