Consider Risk Levels When Treating Polycythemia Vera Before and After Fibrotic Transformation


Risk stratification for survival should not dictate treatment, but stratification for thrombosis risk should play an important role in treatment decisions.

Diagnosing and treating polycythemia vera (PV) can vary before and after fibrotic transformation and considering various risk factors is essential for choosing the best treatment, according to a session at the Society of Hematologic Oncology 2021 Virtual Meeting.

In the session, presenter and Mayo Clinic professor of medicine Ayalew Tefferi, MD, discussed how he approaches patients with PV. Firstly, Tefferi reviewed the diagnostic algorithm he uses for these patients.

Whenever PV is suspected in patients with a Janus kinase 2 (JAK2) mutation and a subnormal serum erythropoietin (sEpo), Tefferi said a confirmed diagnosis is likely. Similarly, patients with a JAK2 mutation and normal sEpo but who have a JAK2 allele burden of 1% or greater are also likely to have a PV diagnosis.

Once a diagnosis is confirmed, Tefferi said the next step is to risk-stratify the patient. Notably, risk stratification for survival should not dictate treatment, but stratification for thrombosis risk should play an important role in treatment decisions. For survival risk stratification, he said the most important risk factors are advanced age and leukocytosis, although clinicians can also consider abnormal karyotypes and SRSF2 mutations.

The current treatment approach for all patients is scheduled phlebotomy to keep hematocrit above 45%, in addition to once-daily low-dose aspirin. In addition to these steps, patients with low-risk disease (defined as those younger than 60 years of age and with no history of thrombosis) could be considered for twice-daily aspirin if they have cardiovascular risk factors, leukocytosis, or persistent microvascular symptoms. Clinicians can also consider pegylated IFN-α if the patient has frequent phlebotomy requirements, protracted pruritus, symptomatic splenomegaly, or persistent microvascular symptoms.

For those with high-risk disease, Tefferi said clinicians should consider hydroxyurea with a 500 mg twice-daily starting dose. If they then have a history of arterial thrombosis, consider twice-daily aspirin, or systemic anticoagulation if the patient has a history of venous thrombosis.

For high-risk patients who are hydroxyurea intolerant or resistant, clinicians can use pegylated IFN-α or busulfan ruxolitinib. Tefferi said ruxolitinib is preferred in the presence of symptoms reminiscent of post-PV myelofibrosis, and busulfan is preferred in older patients.

In addition to these treatment options, Tefferi said there are several new drugs for the treatment of PV, including ropeginterferon, PTG-300, givinostat, or idasanutlin. Although these are all options, Tefferi said he would probably choose pegylated interferon instead of PTG-300 in many cases, because it had a dubious role in high-risk disease and an uncertain role in low-risk disease.

Patients whose disease transforms into myelofibrosis can have the same approach and treatment justification as those with primary myelofibrosis, Tefferi said. There are 2 main options for patients with post-PV myelofibrosis: allogeneic hematopoietic cell transplant for a potentially curative approach, or palliative care. Palliative care options include observation alone or treatments for anemia, symptomatic splenomegaly, constitutional symptoms, as well as involved field radiotherapy for extra-medullary hematopoiesis or experimental therapy.

Finally, Tefferi reviewed available JAK2 inhibitors. Ruxolitinib and fedratinib are both FDA-approved, whereas pacritinib and momelotinib are pending approval. All of these options work well, Tefferi said, although he emphasized that some studies are showing stifled responses to COVID-19 vaccines among patients on JAK2 inhibitors.


Tefferi A. Treating PV Before and After Fibrotic Transformation. Presented at: Society of Hematologic Oncology 2021 Virtual Meeting. Presented September 9, 2021. Accessed September 28, 2021.

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