Polycythemia vera: aspects of its current diagnosis and initial treatment

ABSTRACT

Introduction

Significant advances have been made in the diagnosis and management of patients with polycythemia vera (PV) over the past two decades, but a few important issues remain, either overlooked or controversial.

Areas covered

We discuss making an accurate diagnosis of PV with careful interpretation of hematocrit values, red cell count, and red cell mass when available, and bone marrow histomorphology to distinguish PV from other JAK2^V617F myeloproliferative neoplasms (MPNs). We cover aspects of initial PV treatment with phlebotomy (PHL), its drawbacks in the long term, and alternative strategies. We comprehensively discuss cytoreductive therapy using interferon-alpha or hydroxyurea, with emphasis on patient selection, treatment goals, clinical endpoints, biomarkers and, most importantly, event-free and overall survival.

Expert opinion

A bone marrow biopsy in PV is essential for diagnosis and baseline histomorphology. Both hematocrit and red cell counts should be controlled with both phlebotomy (PHL) and cytoreductive agents. PHL alone is often inadequate in the long term, and cytoreduction is needed for most. Interferon is our preferred first-line agent due to improved survival outcomes. Short-term biomarkers predictive of long-term outcomes are needed to guide optimal therapy and development of new treatments.

KEYWORDS:

• Chronic inflammation
• Hydroxyurea
• Interferon
• Iron deficiency
• Myeloproliferative neoplasm
• Phlebotomy
• Polycythemia vera
• Splenomegaly

Article highlights

• Bone marrow histomorphology is essential for the diagnosis of polycythemia vera (PV) and its distinction from JAK2^V617F essential thrombocythemia and primary myelofibrosis.

• Management of PV is focused on thrombosis risk reduction but must also target prevention of disease progression to myelofibrosis and/or acute leukemia. Clinical and molecular biomarkers for such outcomes are required.

• Phlebotomy alone is inadequate in the long-term management of PV and is associated with additional symptoms of chronic iron deficiency. It does not optimally control disease symptoms and thrombosis risk; it is associated with increased risk of myelofibrosis progression compared to cytoreductive agents.

• Interferon, in the form of peginterferon alpha-2a or ropeginterferon alpha-2b, is our preferred cytoreductive agent based on research by us and others showing high rates and durability of hematologic and molecular responses, as well as myelofibrosis-free and overall survival.

• Randomized trials show the superiority of ropeginterferon alpha-2b overphlebotomy in ELN-defined low-risk disease with respect to complete hematologic response and progression at 2 years, and its superiority to HU in ELN-defined high-risk disease at 6 years with respect to CHR and molecular response.

Acknowledgments

Supported by the David L. Johns Family Fund of the Cancer Research and Treatment Fund (CR&T), New York, NY, USA. We thank Ms. Mara Sanderson for her assistance in the preparation of this manuscript.

Declaration of interest

RT Silver is the Chair of the Data Safety Monitoring Board, SURPASS Study, PharmaEssentia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers of this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by the David L. Johns Family Fund of the Cancer Research & Treatment Fund (CR&T).