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Timely management of polycythaemia vera: considerations and pitfalls

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).1

HU is the most commonly used myelosuppressive therapy for PV2,3

Hydroxyurea (HU) is established as a first-line cytoreductive therapy for patients with polycythaemia vera (PV):2-5

Study of 1,309 patients with polycythaemia vera (PV) in the US3

  • Approx 80% of patients using HU (n=1,080) achieved either a complete (37.1%) or partial (41.6%) response* with HU
  • 56.1% of patients (N=1,080) with available data had haematocrit (HCT) <45%

Retrospective study of 217 patients with PV in Sweden, Denmark and France4

  • The rate of vascular complications was 16% lower for patients receiving HU (11%, n=139) versus phlebotomy alone (27%, n=55); p=0.013

*As per ELN criteria.3

Side effects with HU tend to be infrequent and usually occur at higher doses. However, up to 24% of patients develop intolerance or resistance.7

1 in 8 patients have intolerance to HU
1 in 8 patients have intolerance to HU

Higher rates of HU resistance and intolerance have been observed in some real-world settings. See the data ›

In retrospective studies, patients with intolerance or resistance to HU were found to have an increased risk of mortality, disease progression and complications.7-9

How to recognise HU intolerance and resistance

Modified ELN criteria:11

HU intolerance

  • Haematologic toxicities
    • Absolute neutrophil count <1.0 × 109/L
    • Platelet count <100 × 109/L
    • Haemoglobin <10 g/dL
  • Non-haematological toxicities
    • Fever
    • Manifestations of the mucous membrane
    • Gastrointestinal symptoms
    • Pneumonitis
    • Leg ulcers

HU resistance

  • Thrombosis or bleeding
  • Unacceptable number of phlebotomies to keep HCT <45%†
  • Persisting disease-related symptoms
  • Platelet count >400 x 109/L and/or white blood cell count >10 x 109/L†
  • No reduction of splenomegaly or a reduction <50%

†After at least 3 months with at least 2 g/day of HU or the maximum tolerated dose.11

Mei has been receiving HU for 12 months

Mei
  • She has reported gastric pain and diarrhoea, fatigue, erythema and pruritus, and now has a leg ulcer
  • Her HU dose has been decreased from 1,500 mg per day to 500 mg per day
  • Her HCT is within target (<45%)
  • Her platelet count is higher than target (>400 x 109/L)

HU-related toxicity can prevent effective dosing.12-14

Refer to the HU Summary of Product Characteristics for full details on dosing.

Cutaneous toxicity ›

Maurice has been receiving HU for 2 years

Mei
  • His HCT remains higher than target (>45%)
  • He suffers from symptoms including fatigue and spells of dizziness and confusion
  • His spleen was found to be enlarged at his last examination

Persistent burdensome symptoms and high HCT despite tolerated treatment are indicative of poor response due to HU resistance.3,11

Response criteria ›

The are [real/fictitous] patient cases.
Individual responses may vary. Please refer to the individual SmPCs before prescribing.

What are the risks of uncontrolled PV? 

ELN: European LeukemiaNet

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. JAKAVI® Summary of Product Characteristics. Available at: medicines.org.uk.
  2. Alvarez-Larran A, Perez-Encinas M et al. Risk of thrombosis according to need of phlebotomies in patients with polycythemia vera treated with hydroxyurea. Haematologica 2017;102(1):103-109.
  3. Parasuraman S, DiBonaventura M et al. Patterns of hydroxyurea use and clinical outcomes among patients with polycythemia vera in real-world clinical practice: a chart review. Exp Hematol Oncol 2015;5:3.
  4. Barbui T, Tefferi A et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia 2018;32(5):1057-1069.
  5. Tefferi A, Vannucchi A M, Barbui T. Polycythemia vera: historical oversights, diagnostic details, and therapeutic views. Leukemia 2021;35(12):3339-3351.
  6. Enblom-Larsson A, Girodon F et al. A retrospective analysis of the impact of treatments and blood counts on survival and the risk of vascular events during the course of polycythaemia vera. Br J Haematol 2017;177(5):800-805.
  7. 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.
  8. Marchioli R, Finazzi G et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 2013;368(1):22-33.
  9. 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.
  10. Jentsch-Ullrich K, Eberhardt J et al. Characteristics and treatment of polycythemia vera patients in clinical practice: a multicenter chart review on 1476 individuals in Germany. J Cancer Res Clin Oncol 2016;142(9):2041-2049.
  11. McMullin M F, Wilkins B S, Harrison C N. Management of polycythaemia vera: a critical review of current data. Br J Haematol 2016;172(3):337‑349.
  12. Grunwald M R, Kuter D J et al. Treatment patterns and blood counts in patients with polycythemia vera treated with hydroxyurea in the United States: an analysis from the REVEAL study. Clin Lymphoma Myeloma Leuk 2020;20(4):219-225.
  13. Najean Y, Rain J D. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood 1997;90(9):3370-3377.
  14. Palandri F, Bartoletti D et al. Differential treatment strategy in polycythemia vera patients with stable suboptimal response to hydroxyurea: clinical correlations and impact on survival. Blood 2020;Supplement 1:17.
  15. Stegelmann F, Wille K et al. Significant association of cutaneous adverse events with hydroxyurea: results from a prospective non-interventional study in BCR-ABL1-negative myeloproliferative neoplasms (MPN) - on behalf of the German Study Group-MPN. Leukemia 2021;35(2):628-631.
  16. Barosi G, Mesa R et al. Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project. Blood 2013;121(23):4778-4781.