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Teaching pack: Myeloproliferative neoplasms (PV, ET, myelofibrosis)

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  1. Teaching pack · Cancer · haematologic

    Myeloproliferative neoplasms (PV, ET, myelofibrosis)

    Slow-growing blood cancers in which the marrow makes too many red cells, platelets or scar tissue. Almost all carry a mutation in JAK2, CALR or MPL. Treatment aims at preventing clots, controlling symptoms and, in myelofibrosis, shrinking the spleen.

    Teaching pack: Myeloproliferative neoplasms (PV, ET, myelofibrosis) · OnCo, CC BY 4.0 · not medical advice1 / 8
  2. What it is

    In two paragraphs

    The classical BCR-ABL1-negative MPNs (polycythaemia vera, essential thrombocythaemia, primary myelofibrosis) are clonal diseases driven by JAK-STAT activation: JAK2 V617F in ~95% of PV and ~60% of ET/PMF, CALR in ~25% of ET/PMF, MPL in ~5%. Risk in PV/ET is thrombosis (managed with aspirin, phlebotomy, hydroxyurea or interferon); in myelofibrosis it is cytopenias, splenomegaly, constitutional symptoms and leukaemic transformation (about 10-20%), risk-scored by DIPSS-plus, MIPSS70 and MIPSS70+ v2.0.

    Ruxolitinib (COMFORT-I/II, 2011) was the first JAK inhibitor; fedratinib (2019), pacritinib (2022, for platelets <50) and momelotinib (2023, for anaemic patients) followed. None is disease-modifying: allogeneic transplant remains the only cure for myelofibrosis. Ropeginterferon alfa-2b (2021) is the first approved interferon for PV with evidence of molecular response, and rusfertide (2026), a hepcidin mimetic, is the first drug to control PV erythrocytosis without phlebotomy (VERIFY). CALR-directed antibodies and JAK2 V617F-selective inhibitors are the disease-modifying hope; pelabresib (BET inhibitor) plus ruxolitinib improved spleen response but not symptoms in MANIFEST-2.

    Teaching pack: Myeloproliferative neoplasms (PV, ET, myelofibrosis) · OnCo, CC BY 4.0 · not medical advice2 / 8
  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    PVLow-dose aspirin, phlebotomy to haematocrit <45%; cytoreduction (hydroxyurea or ropeginterferon alfa-2b) for high-risk; ruxolitinib after hydroxyurea failure (RESPONSE); rusfertide to eliminate phlebotomy need (VERIFY, 2026).NCCN Category 1 (ropeginterferon, hydroxyurea)
    ETRisk-adapted (IPSET-thrombosis): observation or aspirin in low risk; hydroxyurea or interferon in high risk; anagrelide second line.not mapped
    Myelofibrosis, intermediate-2/high riskJAK inhibitor for spleen and symptoms: ruxolitinib (COMFORT), fedratinib, pacritinib if platelets <50×10⁹/L, momelotinib if anaemic (MOMENTUM); allogeneic HSCT for eligible patients (the only cure).NCCN Category 1 (ruxolitinib, fedratinib); 2A (pacritinib, momelotinib)
    Anaemia of myelofibrosisMomelotinib, luspatercept (INDEPENDENCE), ESA, danazol, transfusion.not mapped
    Teaching pack: Myeloproliferative neoplasms (PV, ET, myelofibrosis) · OnCo, CC BY 4.0 · not medical advice3 / 8
  4. State of the art

    Where the field stands

    • Four approved JAK inhibitors cover spleen, symptoms, thrombocytopenia and anaemia, but none reverses fibrosis or clears the clone.
    • Interferon is the only drug with consistent molecular responses in PV/ET, and ropeginterferon made it practical.
    • Rusfertide (2026) is the first mechanistically new PV drug in a decade and removes the need for phlebotomy in most patients.
    • The next wave targets the clone itself: mutant-CALR antibodies (e.g. INCA033989), JAK2 V617F-selective inhibitors, and navitoclax/pelabresib combinations with mixed phase 3 results.
    Teaching pack: Myeloproliferative neoplasms (PV, ET, myelofibrosis) · OnCo, CC BY 4.0 · not medical advice4 / 8
  5. History

    How we got here

    1. 1951Dameshek groups the MPNs
    2. 2005JAK2 V617F discovered
    3. 2011Ruxolitinib approved
    4. 2013CALR mutations
    5. 2013Haematocrit target proven
    6. 2019Fedratinib approved
    7. 2021Ropeginterferon alfa-2b approved for PV
    8. 2022Pacritinib for severe thrombocytopenia
    9. 2023Momelotinib for anaemic myelofibrosis
    10. 2026Rusfertide approved for PV
    Teaching pack: Myeloproliferative neoplasms (PV, ET, myelofibrosis) · OnCo, CC BY 4.0 · not medical advice5 / 8
  6. Pipeline

    What is coming

    • Rusfertide (product)
    • Momelotinib (product)
    • Luspatercept (product)
    • Allogeneic stem cell transplantation (technology)
    Teaching pack: Myeloproliferative neoplasms (PV, ET, myelofibrosis) · OnCo, CC BY 4.0 · not medical advice6 / 8
  7. Open problems

    What nobody has solved

    • No disease-modifying therapy in myelofibrosis short of transplant.
    • MPN in blast phase: outcomes as poor as secondary AML.
    • Whether interferon-induced molecular response prevents progression.
    • Sequencing and combining JAK inhibitors with BET, BCL-XL or CALR-directed agents.
    Teaching pack: Myeloproliferative neoplasms (PV, ET, myelofibrosis) · OnCo, CC BY 4.0 · not medical advice7 / 8
  8. Sources

    Read the primary sources

    • NCCN Guidelines: MPN: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1477
    • NCI PDQ: chronic MPN: https://www.cancer.gov/types/myeloproliferative/patient/chronic-treatment-pdq
    • MPN Research Foundation: https://www.mpnresearchfoundation.org/
    • Wikipedia: https://en.wikipedia.org/wiki/Myeloproliferative_neoplasm
    • Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1477
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