Myeloproliferative neoplasms (PV, ET, myelofibrosis)

aka MPN, Polycythaemia vera, Essential thrombocythaemia, Primary 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.

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.

State of the art today

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.

Who it affects

Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

Combined incidence around 2-3 per 100,000 per year; PV and ET are chronic diseases lived with for decades, myelofibrosis has a median survival of about six years.

Group

haematologic

Where the cases are

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Low-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)

Hydroxyurea (hydroxycarbamide)Ropeginterferon alfa-2bRuxolitinibRusfertide

Risk-adapted (IPSET-thrombosis): observation or aspirin in low risk; hydroxyurea or interferon in high risk; anagrelide second line.

NCCN Guidelines: MPN

Hydroxyurea (hydroxycarbamide)Ropeginterferon alfa-2b

Myelofibrosis, intermediate-2/high risk

JAK 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 (p…

RuxolitinibFedratinibPacritinibMomelotinibAllogeneic stem cell transplantation

Anaemia of myelofibrosis

Momelotinib, luspatercept (INDEPENDENCE), ESA, danazol, transfusion.

MomelotinibLuspatercept

Subtypes & biomarkers

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Subtypes

Polycythaemia vera (PV)
Essential thrombocythaemia (ET)
Prefibrotic and overt primary myelofibrosis (PMF)
Post-PV / post-ET myelofibrosis
MPN in blast phase
Triple-negative MPN

Biomarkers clinicians test

JAK2 V617F and exon 12
CALR type 1/2
MPL W515
High-molecular-risk mutations (ASXL1, EZH2, SRSF2, IDH1/2, U2AF1)
DIPSS-plus / MIPSS70+ v2.0
Haematocrit target <45% (CYTO-PV)
Platelet count (pacritinib eligibility)

Target prevalence in this cancer

Target / alteration	Prevalence	Measure	Source
JAK2	60-95%	JAK2 V617F by subtype	doi.org

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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1951Dameshek groups the MPNs
Proposes that PV, ET, CML and myelofibrosis are related myeloproliferative disorders.
2005JAK2 V617F discovered
Four groups report the mutation in most PV and half of ET/PMF; the first molecular marker for BCR-ABL1-negative MPN.
JAK2
2011Ruxolitinib approved
COMFORT-I/II: spleen and symptom benefit in myelofibrosis; the first JAK inhibitor.
Ruxolitinib
2013CALR mutations
Klampfl and Nangalia find CALR exon 9 mutations in most JAK2-negative ET/PMF.
2013Haematocrit target proven
CYTO-PV: keeping haematocrit <45% cuts cardiovascular death and major thrombosis in PV.
2019Fedratinib approved
JAKARTA; the second JAK inhibitor after an eight-year gap.
Fedratinib
2021Ropeginterferon alfa-2b approved for PV
PROUD/CONTINUATION-PV: superior long-term haematologic and molecular response versus hydroxyurea.
Ropeginterferon alfa-2b
2022Pacritinib for severe thrombocytopenia
Pacritinib
2023Momelotinib for anaemic myelofibrosis
MOMENTUM: symptom, spleen and transfusion-independence benefit versus danazol.
Momelotinib
2026Rusfertide approved for PV
VERIFY: hepcidin mimetic controls erythrocytosis without phlebotomy; FDA approval August 2026.
Rusfertide

Pipeline

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Not mapped hereHepcidin mimetic peptide

Rusfertide · Mimrylo

Not mapped hereSmall-molecule JAK1/JAK2/ACVR1 inhibitor

Momelotinib · Ojjaara / Omjjara

Not mapped hereErythroid maturation agent (activin receptor IIB ligand trap, Fc fusion)

Luspatercept · Reblozyl

Allogeneic stem cell transplantation

Open problems

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.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov

Myeloproliferative neoplasms (PV, ET, myelofibrosis)

condition: Myeloproliferative neoplasms

Open on ClinicalTrials.gov →

within

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Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Mays Cancer Center at UT Health San AntonioSan Antonio, TX, USNCI clinical
via this cancer, Ruxolitinib
Fred & Pamela Buffett Cancer CenterOmaha, NE, USNCI clinical
via Allogeneic stem cell transplantation
Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensive
via Allogeneic stem cell transplantation
Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CA
via Allogeneic stem cell transplantation
Masonic Cancer Center, University of MinnesotaMinneapolis, MN, USNCI comprehensive
via Allogeneic stem cell transplantation
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensive
via Allogeneic stem cell transplantation

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Myeloproliferative neoplasms

Generated from this cancer's standard of care, biomarkers, and pipeline · 17 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example JAK2 V617F and exon 12, CALR type 1/2, MPL W515, High-molecular-risk mutations, DIPSS-plus / MIPSS70+ v2.0), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include Polycythaemia vera, Essential thrombocythaemia, Prefibrotic and overt primary myelofibrosis.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

PV

For my situation (pv), which of the standard options do you recommend and why?
Why: Guideline options include: Low-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).
Am I a candidate for Hydroxyurea (hydroxycarbamide), Ropeginterferon alfa-2b, Ruxolitinib or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

ET

For my situation (et), which of the standard options do you recommend and why?
Why: Guideline options include: Risk-adapted (IPSET-thrombosis): observation or aspirin in low risk; hydroxyurea or interferon in high risk; anagrelide second line.
Am I a candidate for Hydroxyurea (hydroxycarbamide), Ropeginterferon alfa-2b, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Myelofibrosis, intermediate-2/high risk

For my situation (myelofibrosis, intermediate-2/high risk), which of the standard options do you recommend and why?
Why: Guideline options include: JAK 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).
Am I a candidate for Ruxolitinib, Fedratinib, Pacritinib or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Anaemia of myelofibrosis

For my situation (anaemia of myelofibrosis), which of the standard options do you recommend and why?
Why: Guideline options include: Momelotinib, luspatercept (INDEPENDENCE), ESA, danazol, transfusion.
Am I a candidate for Momelotinib, Luspatercept, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

Are there clinical trials I could join, for example of Rusfertide, Momelotinib, Luspatercept, Allogeneic stem cell transplantation?
Why: Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?
Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
Why: Supportive care improves quality of life and helps patients complete treatment.
I read that “No disease-modifying therapy in myelofibrosis short of transplant”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “MPN in blast phase: outcomes as poor as secondary AML”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.

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Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

Key papers

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rctThe Lancet 2023changed practice

MOMENTUM: momelotinib versus danazol for myelofibrosis patients with anaemia after a prior JAK inhibitor

MOMENTUM addressed the biggest gap left by ruxolitinib: patients whose anaemia makes standard JAK inhibition hard to give. Momelotinib is now the preferred option for anaemic, previously treated myelofibrosis and is being adopted in first line for anaemic patients. The absolute symptom benefit is modest and durable disease modification has not been shown.

rctNew England Journal of Medicine 2012changed practice

COMFORT-I: ruxolitinib, the first JAK inhibitor, versus placebo for myelofibrosis

COMFORT-I turned the 2005 discovery of the JAK2 V617F mutation into the first effective medicine for myelofibrosis, transforming symptom control for a disease with no prior standard. Ruxolitinib is still the reference first-line therapy, with fedratinib, pacritinib and momelotinib as alternatives for cytopenic patients. It does not eliminate the malignant clone or reverse fibrosis in most patients.