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PV FAQ 2023
Best Practices for Polycythemia Vera: Expert Answers to Frequently Asked Questions From the Community

Released: September 19, 2023

Douglas Tremblay
Douglas Tremblay, MD
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Key Takeaways
  • Performing bone marrow biopsy is beneficial for all patients with polycythemia vera (PV) to provide a baseline against which to measure future development of fibrosis or other pathology.
  • Interferon may be a more appropriate initial cytoreductive treatment for younger patients who may wish to have children, due to risk of birth defects associated with hydroxyurea. 
  • Ruxolitinib is more effective than hydroxyurea for control of symptoms associated with PV, but most patients experience weight gain with ruxolitinib treatment.

In this commentary, Douglas Tremblay, MD, answers audience questions from a live webinar series titled, “A Community Practitioner’s Guide to Contemporary Management of Polycythemia Vera: Data Review and Case Challenges Illustrating Current Best Practice.”

Should bone marrow biopsy be performed in all patients with polycythemia vera (PV)?
Dr Tremblay: I perform a bone marrow biopsy in all patients with PV, but that is not universal practice among myeloproliferative neoplasm (MPN) specialists. From a purely diagnostic perspective, a patient with very high hematocrit, low serum erythropoietin, and JAK2 mutation does not require a bone marrow biopsy to meet criteria for a PV diagnosis. However, there are 3 major reasons to biopsy all patients diagnosed with PV. First, patients with bone marrow fibrosis of ≥1 are at higher risk of progressing to myelofibrosis, so it is important to identify these patients for more frequent and vigilant monitoring. Second, bone marrow biopsy may identify additional pathologies requiring treatment, such as chronic lymphocytic leukemia or multiple myeloma. Third and most important, performing bone marrow biopsy at the time of diagnosis provides a baseline for future comparison. For example, when evaluating fibrosis in a patient with a 5-year history of PV and current signs of myelofibrotic progression (eg, spleen enlargement, loss of phlebotomy dependence), it is helpful to have a previous bone marrow sample to determine the developmental timeline of the fibrosis. That said, many patients prefer not to undergo the biopsy procedure. For a patient with high hematocrit who has experienced an unprovoked deep vein thrombosis, I presume that the bone marrow would show some evidence of MPN and treat them with cytoreductive therapy. Whether the bone marrow reveals PV, essential thrombocythemia, or prefibrotic myelofibrosis, there is convincing evidence that patients with a history of blood clots are at risk for additional clots and that cytoreductive therapy can reduce that risk.  

What factors impact your initial choice between interferon and hydroxyurea treatment?
Dr Tremblay: Some data suggest patients with early-stage PV experience greater benefit with interferon than with hydroxyurea, but the level of confidence is not high enough to make a strong recommendation. I prefer to treat younger patients with interferon simply because of the association of hydroxyurea with higher risk of birth defects, both for women and for men. It’s worth noting that patients at high risk of thrombosis need to continue cytoreductive treatment throughout pregnancy, so the recommendation is to treat patients who may become pregnant with interferon. If a patient treated with hydroxyurea wants to conceive, I switch them to interferon 2 to 3 months beforehand.

Can you provide any guidance on when a patient should be switched from hydroxyurea to ruxolitinib treatment?
Dr Tremblay: The European LeukemiaNet recommendations provide specific definitions for hydroxyurea resistance and intolerance, but the essential factor is that the patient is not doing well on hydroxyurea, which usually means uncontrolled symptoms of the disease. Ruxolitinib is a more effective treatment than hydroxyurea for symptom control, particularly itching, splenomegaly and night sweats. In terms of hematologic benefit, hydroxyurea can be increased to 2 g/day (administered as 1000 mg twice daily), which is then considered treatment failure if hematologic control is not achieved at that dose. It is possible to continue increasing the dose, but hydroxyurea resistance itself is a high-risk marker which would suggest a treatment switch.

What is your experience with weight gain on ruxolitinib?
Dr Tremblay: A real-world analysis of patients treated with ruxolitinib at our center found that weight gain is nearly universal; approximately 85% of patients will gain some weight. The degree of weight gain is variable; many patients will only gain a few pounds, but some may gain as much as 20 or 30 pounds. The mechanisms underlying this are unclear. Some studies suggest that ruxolitinib affects leptin signaling and causes hyperphagia (overeating), while others report effects on metabolism and peripheral fat. My center recently published a case report showing reduced metabolism over time in 2 patients treated with ruxolitinib. Of interest, we have found that fedratinib does not cause weight gain, so this quality of ruxolitinib may be unique among the JAK inhibitors. It is also unclear how best to manage this. I discuss the potential for weight gain with all patients when starting ruxolitinib and provide diet and exercise counseling as the main tool, but sometimes dose reduction is necessary.   

I recall learning in the past that PV should be managed by monitoring ferritin as well as hematocrit. Is ferritin no longer considered?
Dr Tremblay: Before publication of the CYTO-PV study in 2013, many hematologists would target ferritin, which was a familiar marker because of its use to determine phlebotomy need in patients with hemochromatosis. Now data are available showing that hematocrit <45% is the only metric demonstrated to reduce the risk of thrombosis in PV, so the recommendation is to target hematocrit without regard to ferritin level. If the hematocrit is 45.2%, I phlebotomize and if it is 44.5% I do not—the target should be considered that exact. In practice, I have found that patients’ ferritin may fall below 20 µg/L, which indicates very severe iron deficiency. Phlebotomy largely exerts its effects by inducing iron deficiency rather than by removing red blood cells; newer ferritin-modulating and hepcidin-modulating agents capitalize on this by acting to trick the bone marrow into thinking it is iron deficient.

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