An overview of the treatment options for patients with polycythemia vera.
Rami Komrokji, MD: We establish the diagnosis and we think about the risk of those diseases. Can you walk us through the factors that make you initiate treatment? What are the treatment options for patients with PV [polycythemia vera]?
Jeanne Palmer, MD: Absolutely. When I see somebody and I’ve diagnosed them with PV, in many cases, a lot of the decisions on therapy can be a shared decision-making process. There are multiple options. It’s important to understand what’s important to the patient and the risks for different complications related to therapy.
In general, whenever somebody comes in and they’re diagnosed with polycythemia vera, absolutely try to begin aspirin as well as phlebotomy. I usually start phlebotomy, especially in somebody who has presented with a thrombotic event. I’ll do phlebotomy weekly to make sure I can lower their hematocrit. The hematocrit goal for patients is less than 45%. This 45% has been proven in a trial where they looked at keeping it less than 50% or less than 45% and 45% was superior with regard to cardiovascular events. This is important to do. Because women tend to have a lower hemoglobin and hematocrit than men, the goal is often 42%. I often try to keep women below that 42%. If they’re struggling with keeping below that and with iron deficiency, etc, then sometimes I’ll let them go a little higher.
When somebody is younger than 60 and doesn’t have any significant thrombotic events, phlebotomy and aspirin are sufficient. However, once the patient is older than 60 [years] or if they’ve had some type of thrombotic event, whether it be arterial or venous, it’s important to do cytoreductive therapy. When I approach cytoreductive therapy, this is where it becomes a shared decision-making process. The most commonly used therapy is hydroxyurea. It’s easy and quick and it’s a pill. This pill has been around for a number of years. As Ruben discussed with essential thrombocythemia, there can be toxicities, such as GI [gastrointestinal] and mucocutaneous toxicities. A lot of patients fear that it may increase the risk of leukemia, which has never been borne out in well-done studies. But hydroxyurea is a very good steadfast medication to use.
More recently, one of the exciting things that’s come out is the ropeginterferon or the novel pegylated interferon. For years, we’ve been talking about using pegylated interferon and use Pegasys, which is the commercially available one that has been present all along. However, ropeginterferon has the advantage of being an every-2-week injection vs a weekly injection.
The nice part about ropeginterferon is we have very good clinical data to support it. There’s the PROUD-PV [NCT01949805] and the CONTINUATION-PV [NCT01949805], which is a study that randomized patients to either ropeginterferon or hydroxyurea. These patients were monitored. PROUD-PV was the first year and CONTINUATION-PV was the long-term follow-up at 3 years. There are a few notable things about these patients. In the first year, blood cell counts were controlled equally. Patients were well controlled with either ropeginterferon or hydroxyurea. But within that first year and more so after the first year, we start to see that patients will have a decrease in JAK2 mutational allele burden at times. This isn’t for every patient, but there are a number of patients who will have it. Some of the patients will get less than 10%. Then a small fraction will go away.
This suggests, as does a lot of preclinical data, that the interferons in general may have a modifying effect on the disease or change the natural history of disease. There are preclinical data suggesting it suppresses the JAK2 clone, although there’s probably some advantage even in patients who don’t have the JAK2 mutation. But this medication can be beneficial. That’s where I talk to patients and say, “This is what we know about these 2 different treatments,” and oftentimes let them decide what they’re willing to try to do. Unfortunately, sometimes it comes down to what I can get paid for, because interferons can be quite costly. But interferons are a very good choice that I always discuss, even in low-risk patients who aren’t necessarily older than 60 or who haven’t had a thrombotic event.
The Low-PV study [NCT0300332] looked at using ropeginterferon in that setting, and that was also beneficial. I don’t think the use of cytoreductive agents necessarily needs to be limited to patients who are aged 60 years or older or high risk. The other setting where we’d use cytoreductive therapy in a patient who doesn’t necessarily fall into the high-risk category is in patients who have symptoms related to iron deficiency. Phlebotomy basically makes somebody iron deficient. Iron deficiency has a lot of symptoms. It can cause fatigue and restless leg syndrome. I’ve even found that mood can be impaired. Oftentimes, I’ll choose cytoreductive therapy so I can start to replace the iron very gently and control their hemoglobin and hematocrit through another mechanism.
One of the other agents that’s being used quite a bit in polycythemia vera is ruxolitinib. This was borne out in the RESPONSE and RESPONSE-2 studies [NCT01243944 and NCT02038036, respectively]. In this, they used patients who were on hydroxyurea and they were randomized to hydroxyurea or ruxolitinib. They found that they had very good blood cell count control using ruxolitinib. There’s also a decreased risk of thrombotic events and improvement in symptom burden. Ruxolitinib is definitely an option that I consider, especially in patients who don’t tolerate hydroxyurea or have a large spleen and a significant symptom burden.
Rami Komrokji, MD: Absolutely. With all those new therapies, we have to revisit how we assess risk. The classical [risk assessment] by age and presence of venothrombotic events is changing. There are other factors, like leukocytosis sometimes correlates with events more. Nowadays, integration of checking molecular profiling for those patients and identifying higher risk mutations is essential in the management. I’m excited about the ropeg potential alteration of the natural history of the disease, and I hope that there will be generalization of use of those drugs more. But I also agree with you [about using those drugs] even in younger patients who aren’t considered higher risk by the guidelines. Sometimes I discuss with them that there’s a treatment that could alter the natural history of the disease.
Transcript edited for clarity.