How I Treat: a 29-Year-Old Patient With Polycythemia Vera

Firas El Chaer, MD, University of Virginia Cancer Center, Charlottesville, Virginia, provides a case history and explains the course of treatment he chose for a patient with polycythemia vera (PV).

In this case, the patient is a 29-year-old with past medical issues of endometriosis and anxiety, who was previously treated with hydroxyurea. Dr El Chaer chose the treatment of ropeginterferon alfa-2b for this patient. 

Transcript:

Hello, my name is Firas El Chaer. I'm a medical oncologist and hematologist at the University of Virginia. Today we'll be discussing a patient case revolving around polycythemia vera. This patient is a 29-year-old female with past medical issues of endometriosis and anxiety. She originally presented with erythromelagia, bone pain, joint pain, fatigue, and right lower extremity swelling. Upon further investigation, her labs showed a hemoglobin of 18 grams per deciliter. Her white panel was normal with a normal differential, and her platelet count were normal at 357,000.

Further testing showed that her erythropoietin level was 1.2, which was low or suppressed, and she subsequently underwent a bone marrow biopsy. It was hypercellular with sprouting erythropoiesis. There was no increase in blasts. However, there were increased atypical megacaryocyte and the reticulin stain showed no increase in fibrosis. Chromosomal analysis was normal and next gen sequencing showed a JAK2 V617F mutation, which was detected at the variant elite frequency of 46%.

Because of that constellation of symptoms and diagnostic workup, the patient was diagnosed with polycythemia vera. And her right lower extremity, subsequent ultrasound showed a deep vein thrombosis, so she was started on anticoagulation and the referring provider started her on hydroxyurea as a form of cytoreduction. A few months later, the patient started developing recurrent unexplained fevers and she had an extensive infectious workup, which was negative. Hydroxyurea thought to be the culprit. It was stopped and the fever resolved. However, the referring oncologist did restart hydroxyurea and fever reoccurred. The patient was counseled to switch therapy and interferon therapy was offered, but the patient was concerned about the side effects. So she was referred to me for further evaluation. When I saw her in my clinic, her counts were pretty much controlled. Her hemoglobin was 12 (g/dL) and her white count was normal and her platelets were normal. At that point we sat down and we discussed a few options for her.

For our patient case, we had 4 options. The first one was to continue hydroxyurea, and in this particular patient case, I would not do that because the patient showed intolerance because of the recurrent fever. The other option was ropeginterferon, which we went with, and I'll explain shortly the data behind that. The third option was ruxolitinib. This is  a reasonable option as well. At the time, we did not have the results of the MAJIC-PV trial. The fourth option was switch to anagrelide. While this is an option, it's not my preferred regimen, especially with the data that we have much more robust data about ropeginterferon and ruxolitinib in this particular setting.

We chose ropeginterferon based on the PROUD-PV and the CONTINUATION-PV trials, which actually compared ropeginterferon, which is a novel monopegylated interferon, to hydroxyurea to treat patients with polycythemia vera. These trials focus on patients with early stage PV defined by event the WHO 2008 criteria, and patients who either had no prior cytoreductive treatment or less than 3 years of previous hydroxyurea use. It's important to know that approximately 35% of patients in the ropeginterferon group in the PROUD-PV trial and 32% of the CONTINUATION-PV trial were pretreated with hydroxyurea. In the PROUD-PV trial, the primary endpoint was achieving a complete methodologic response with a normal spleen size reduction at normal spleen size at 12 months. In that trial, the PROUD-PV, 21% of patients in the ropeginterferon group achieved this endpoint compared to 28% in the hydroxyurea group.

In the CONTINUATION-PV trial at 36 months, we saw a significant improvement in complete hematologic response with improved disease burden. 53% of patients in the ropeginterferon group met this primary endpoint versus 38% of the hydroxyurea group with a significant statistical significance. One of the unique aspects of interferon therapy is association with molecular responses in PV. While the long-term clinical significance of these molecular remissions, particularly in terms of thrombotic risk and mortality, it's still being evaluated. It is a promising feature.

Now, additionally, ropeginterferon offers a more favorable toxicity profile compared to conventional interferons, and it's a prolonged activity enables less frequent dosing, which can be significant advantage for the patients. And the safety data is reassuring. Serious treatment-related adverse events were low in those trials. occurring in about 2% of patients on ropeginterferon and then 4% on hydroxyurea. The adverse events in the ropeginterferon arm were primarily related to liver enzymes elevations. While those in the hydroxyurea group were basically cytopenias.

As we discussed as well, ruxolitinib is an option for this patient. This is based on the MAJIC-PV trial, which was a randomized phase 2 trial comparing RUX or ruxolitinib to the best available therapy in patients with polycythemia vera who were resistant or intolerant to hydroxyurea. Ruxolitinib showed significantly higher complete remission rates. It was 3% versus 26% in the best available therapy R, and it showed longer duration of complete remission compared to the best available therapy. Symptom improvements were much more durable with ruxolitinib, and event-free survival was superior in patient achieving CR. Those treated with ruxolitinib, importantly molecular responsive, including reductions in JAK2 V617F lead burden were more frequent with ruxolitinib and correlated with improved PFS, EFS and overall survival. That trial, the MAJIC-PV trial, established ruxolitinib as an effective treatment for PV patients whose disease is resistant or intolerant to hydroxyurea, highlighting for the first time the connection between molecular response and clinical outcomes and the safety profile of ruxolitinib was consistent with previous findings. There was no new safety concerns. 

In this case, the patient was switched to ropeginterferon. She's now about a year and a half on treatment. She's doing excellent. She self-injects at home. Her counts have been controlled. She remains on anti-coagulation for her history of the DVT. She did not develop any side effects from ropeg, and now she's actually on the once monthly dosing and continues to do well.

Learn More About This Case Here:

How I Treat: Polycythemia Vera