Polycythemia Vera: Treatment Goals & Risk Stratification

Prithviraj Bose, MD:The risk stratification in polycythemia vera [PV] has really not changed in a long, long time. So the formal risk stratification still uses only age and history of thrombosis. So if you look at our case here, the lady is 58 years old and has never had a clot. Because of that, she would be considered low risk, according to the conventional way of risk stratifying patients.

Traditionally, low-risk patients with PV have been managed with phlebotomy and aspirin, and that remains the standard. Not everyone with PV needs cytoreductive therapy; however, for those who do, there are several options available. In the United States, hydroxyurea tends to be predominantly the drug of choice in the frontline setting. However, one could also use pegylated interferon. We now know from a large randomized trial that there is really no difference in any outcome between these 2 drugs. So interferon would also be a reasonable frontline alternative. Consensus guidelines have suggested the use of interferon in young patients with a long life expectancy because of the continued controversy, although completely unproven over the leukemogenicity of hydroxyurea.

So again, this has never been shown, but there is some fear that persists, and therefore consensus guidelines have suggested the use of interferon instead in young patients. And as I just said, randomized trials have shown that there really is no difference between pegylated interferon and hydroxyurea in the frontline setting. Now, it’s very rare to need a splenectomy in PV. I have not encountered this. Rarely I’ve had to do it in myelofibrosis, where generally the spleen is more of a problem. But one could envision a role for it if the spleen were really troublesome to the patient. However, again, this would be a very unusual situation, especially now that we have ruxolitinib approved in PV, which is a particularly good drug for splenomegaly.

Regarding the dosing of hydroxyurea, there is really no right answer. One usually starts based on experience and based on one’s assessment of how proliferative the disease is. So I really don’t want to quote a number. However, guidelines do say that the maximum is 2 grams a day. I never exceed that. I will point out that it’s not common for patients to be able to tolerate 2 grams a day in my experience. And some real-world studies have shown that very few patients get up to that dose. But if a patient tolerates it well, I will go up to that dose to control their blood counts, eliminate the need for phlebotomy, shrink the spleen if it’s enlarged, etc.

Transcript edited for clarity.

Case: 58-Year-Old Woman Diagnosed With Polycythemia Vera

November 2018

• A 58-year old woman presents to PCP complaining of abdominal pain, dizziness and headaches
• PE: BP 140/85; Splenomegaly ~6 cm below left costal margin
• PMH: No prior history of thrombosis
• Lab values:
  • HGB: 17.1 g/dL
  • Hct: .50 L/L
  • RBC: 71 x 10¹²/L
  • WBC: 13.2 x 10⁹/L
  • Serum EPO: 4.1 mU/mL
• Bone Marrow Biopsy: Erythroid hyperplasia
• Cytogenetics: JAK-V617Fmutation