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The symptom burden, complications and prognosis of polycythaemia vera

What is polycythaemia vera?

Myeloproliferative neoplasms (MPNs) are a group of myeloid malignancies, including:1

  • polycythaemia vera (PV)
  • essential thrombocythaemia (ET)
  • primary myelofibrosis (PMF)

PV is the most common of these three MPNs, with an annual incidence of 0.7 to 2.6 per 100,000 in Europe.2

These MPNs are associated with mutations to the JAK2, CALR and MPL genes and are characterised by stem-cell-derived myeloproliferation.1 Most patients with PV have a mutation in the JAK2 gene.1

Mutation: JAK2-V617F JAK2 exon 12 CALR MPL
PV (% of patients) 96% 3% rare rare
ET (% of patients) 55% rare 15%-24% 4%
PMF (% of patients) 65% rare 25%-35% 8%

Criteria for diagnosis5,6

JAK2-mutation positive PV diagnosis requires both criteria

1

Evidence of erythrocytosis

  • HCT >52% for men; >48% for women, or
  • Red cell mass >25% above mean normal predicted value
2

Presence of JAK2 mutation

JAK2-mutation negative PV diagnosis requires all major criteria + one ‘A’ minor criterion or two ‘B’ minor criteria

Major

1

Evidence of erythrocytosis

  • HCT ≥60% for men; ≥56% for women, or
  • Red cell mass >25% above mean normal predicted value
2

Absence of JAK2 mutation

3

No cause of secondary erythrocytosis

4

Bone marrow histology consistent with PV

Minor A

A1

Palpable splenomegaly

A2

Presence of an acquired genetic abnormality in the haematopoietic cells (excluding BCR-ABL1)

Minor B

B1

Thrombocytosis (platelet count >450 x 109/L)

B2

Neutrophil leukocytosis (neutrophil count >10 x 109/L in non-smokers, ≥12.5 x 109/L in smokers)

B3

Radiological evidence of splenomegaly

B4

Low serum erythropoietin

PV diagnosis requires all three major criteria, or the first two major criteria + the minor criterion

Major Minor

1

Evidence of erythrocytosis

  • Hb >16.5 g/dL for men; >16.0 g/dL for women, or
  • HCT >49% for men; >48% for women, or
  • Red cell mass >25% above mean normal predicted value
2

Hypercellularity with trilineage proliferation

  • Bone marrow biopsy showing hypercellularity for age including prominent erythroid, granulocytic and megakaryocytic proliferation with pleomorphic, mature megakaryocytes

3

Presence of JAK2 or JAK2 exon 12 mutation

1

Subnormal serum erythropoietin level

Anya, 51, was diagnosed with PV as a result of abnormal blood counts found during a routine test.

  • With evidence of raised haemoglobin, haematocrit or red blood cell mass being major diagnostic criteria,5 most cases of PV are discovered by chance7
  • Approximately 30% of cases are diagnoses following a thrombotic complication7
  • Diagnosis due to presentation with PV-associated symptoms is less common7

The median age at diagnosis is 50-60 years.7

Anya

Anya is a fictional patient.

What is the prognosis?

Although a relatively indolent disease, PV does decrease life expectancy versus the general population8,9

Median overall
survival8

14.1

years

n=337 (44% followed to death)

Median survival in high‑risk patients8

8.3

years

n=155 (risk based on a prognostic scoring model involving age, leukocyte count and venous thrombosis)

Prognostic factors associated with increased risk of mortality8,10,11

  • Advanced age (defined by BSH as ≥65 years)6
  • Male sex
  • Leukocytosis
  • Venous thrombosis
  • Haematocrit >45%
  • Resistance to hydroxyurea therapy
What are common symptoms of PV? 

BCR-ABL: breakpoint cluster region-Abelson fusion gene; BSH: British Society for Haematology; CALR: calreticulin; HCT: haematocrit; JAK2: Janus kinase-2; JAK/STAT: Janus kinase/ signal transducer and activator of transcription; MPL: myeloproliferative leukaemia protein; WHO: World Health Organization

JAKAVI® (ruxolitinib) is indicated for adult patients with PV who are resistant to or intolerant of hydroxyurea (also referred to as hydroxycarbamide in the UK).12

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis online through the pharmacovigilance intake (PVI) tool at www.novartis.com/report or alternatively email medinfo.uk@novartis.com or call 01276 698370.

References
  1. Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk-stratification and management. Am J Hematol 2020;95(12):1599-1613
  2. Moulard O, Mehta J et al. Epidemiology of myelofibrosis, essential thrombocythemia, and polycythemia vera in the European Union. Eur J Haematol 2014;92(4):289-297
  3. de Freitas R M, da Costa Maranduba C M. Myeloproliferative neoplasms and the JAK/STAT signaling pathway: an overview. Rev Bras Hematol Hemoter 2015;37(5):348-353
  4. Fox S, Griffin L, Robinson Harris D. Polycythemia vera: rapid evidence review. Am Fam Physician 2021;103(11):680-687
  5. Barbui T, Thiele J et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J 2018;8(2):15
  6. McMullin M F, Harrison C N et al. A guideline for the diagnosis and management of polycythaemia vera. A British Society for Haematology Guideline. Br J Haematol 2019;184(2):176-191
  7. Passamonti F. How I treat polycythemia vera. Blood 2012;120(2):275-284
  8. Tefferi A, Rumi E et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia 2013;27(9):1874-1881
  9. Tefferi A, Vannucchi A M, Barbui T. Polycythemia vera: historical oversights, diagnostic details, and therapeutic views. Leukemia 2021;35(12):3339-3351
  10. Alvarez-Larran A, Pereira A et al. Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood 2012;119(6):1363-1369
  11. Marchioli R, Finazzi G et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 2013;368(1):22-33
  12. JAKAVI® Summary of Product Characteristics. Available at: www.medicines.org.uk (for GB) or www.emcmedicines.com (for NI). Accessed November 2024