The Evolving Treatment Landscape of Polycythemia Vera


Ruben Mesa, MD:There are many exciting things ongoing with polycythemia vera. First, the development of the NCCN guidelines have helped to really highlight, for the treating physicians, the importance of control of all of the counts, not just the hematocrit, the importance of assessment of symptoms in splenomegaly, the prompt and appropriate use of cytoreductive therapy with hydroxyurea, but also recognizing the appropriateness and timing of changing that cytoreductive therapy to ruxolitinib when indicated.

Next, I’m excited about new therapies in the pipeline. Long-acting interferons, of which there’s at least 2—pegylated interferon and ropeginterferon alpha-2a—have been shown to be at least equivalent to hydroxyurea as upfront therapy. As I’ve shared with patients, ruxolitinib and interferons are good drugs for patients with polycythemia vera. It’s really likely that, in the future, we’ll probably see less use of hydroxyurea and more use of these other agents, which clearly are more active and more effective.

I’m excited about other drugs in the pipeline for more difficult cases. For cases that are longer and have unmet needs—everything ranging from nutlin analogs to histone deacetylase inhibitors—there’s potential of benefit of combinations with ruxolitinib and other approaches, including with interferon and other therapies.

Now our greatest unmet need probably still remains the unclear nature of why patients with polycythemia vera progress. We know that patients who respond well to ruxolitinib probably have a decreased likelihood of progression. We know individuals who have had a great response to interferon may have a decreased risk of progression. But at the moment, we can’t track that. We don’t know what the surrogate markers are for progression. We can’t measure that, nor can we yet design therapies specific to inhibiting progression. So, if we were to be able to solve the question as to why patients progress, we would be in a much better place. But all of that said, we have a much deeper bench of options for treating our patients with polycythemia vera in a deeper more holistic way, and I think we clearly are making important advances.

Transcript edited for clarity.

June 2016

  • A 49-year old male presents with headache, fatigue, and pain under his left ribs
  • PMH includes depression and newly diagnosed hypertension
  • Physical Exam: BP, 160/90; Abdominal exam reveals splenomegaly — spleen palpable 6 cm below costal margin
  • Laboratory values:
    • Hb=20.7 g/L
    • HCT= 59.4%
    • WBC=10.2x109/L
    • Platelets= 325 x109/L
  • Bone marrow biopsy:
    • MF-1 fibrosis and megakaryocytic hyperplasia with atypia
    • JAK2-positive
  • Patient was started on phlebotomy as needed and aspirin 81 mg

October 2016

  • Patient returns 4 months later with continued headache and dizziness
  • He has had 3 phlebotomies in the past 3 months
  • Patient was started on hydroxyurea 1000 mg/day

January 2017

  • Patient returns 3 months later with abdominal fullness, continued fatigue, difficulty concentrating, fever, and leg ulcer
  • Laboratory values:
    • Hb= 22.4 g/L
    • HCT= 65.3%
    • WBC=13.3x109/L
    • Platelets=153x109/L
  • Patient is started on ruxolitinib
Recent Videos
Related Content