The Future of Polycythemia Vera Treatment

Prithviraj Bose, MD:I think the obvious unmet need, the one that comes first to mind with regard to PV [polycythemia vera] is that we really don’t have a drug that can prevent progression to myelofibrosis or progression to AML [acute myeloid leukemia]. The latter is a dreadful diagnosis. It’s frankly a catastrophic event for the patient. Survival is very poor when MPNs [myeloproliferative neoplasms] transform to AML. So that is clearly the biggest unmet need, in my opinion. In terms of strategies that have been pursued, there is now interest in MDM2 inhibition as a new therapeutic approach in PV. We have data on, like, 11 patients from ASH 2017 [the American Society of Hematology Annual Meeting & Exposition], so a very small number of patients at this point. But there are companies that are pursuing MDM2 inhibitors in PV.

There are not a whole lot of new agents being pursued in PV, but there are a few. HDAC inhibitors have been studied in PV for a long time, and there is 1 called givinostat, which I believe is still being developed for PV. There is a new long-acting interferon formulation called ropeginterferon-alfa-2b, which predominantly has been trialed in Europe and recently got a positive opinion from the EMA [European Medicines Agency] there. This has been developed in the frontline setting, actually, in a trial versus hydroxyurea, to which it was noninferior. So again, that’s an interferon approach. MDM2 inhibitors and small molecules have been studied. The clinical data we have so far are fairly limited, just about, I think it was about 10 or 11 patients at ASH 2017, but multiple companies are pursuing MDM2 inhibitors. A very new kid on the block is what’s called a hepcidin mimetic. That is another class of agents that’s being developed. So there are a few things on the horizon for PV beyond JAK inhibition.

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