# Primary myelofibrosis

Source: https://onco.cc/cancers/primary-myelofibrosis/  
OnCo record `primary-myelofibrosis` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Primary myelofibrosis is a blood cancer in which the marrow scars over, the spleen swells and patients become anaemic and exhausted. JAK inhibitors, ruxolitinib first (COMFORT) and then fedratinib, pacritinib and momelotinib (MOMENTUM), shrink the spleen and relieve symptoms; only a donor stem cell transplant can cure it.

## Summary

Primary myelofibrosis arises from a haematopoietic stem cell carrying JAK2 V617F (about 60 percent), CALR (about 25 percent) or MPL (5 to 8 percent), or none of the three (triple negative, the worst group), with additional high-risk mutations in ASXL1, SRSF2, EZH2, IDH1/2 and U2AF1. The clone drives cytokine release and megakaryocyte abnormalities that scar the marrow; blood production moves to the spleen and liver, which enlarge, and patients develop anaemia, constitutional symptoms, early satiety and bone pain. A prefibrotic phase resembles essential thrombocythaemia. Risk scores (IPSS, DIPSS-plus, MIPSS70 and MIPSS70-plus v2 with mutations and cytogenetics) predict survival and steer the transplant decision; about one in five progress to blast phase, for which no treatment reliably works.

JAK inhibitors treat the disease's consequences. Ruxolitinib, the first, shrank the spleen by 35 percent or more in 41.9 percent of patients against 0.7 percent on placebo at 24 weeks in COMFORT-I (2012), and beat best available therapy in COMFORT-II, with symptom scores halving in nearly half; approval came in 2011 and a survival advantage emerged in pooled long-term data. Fedratinib (JAKARTA, 2019 approval) works after ruxolitinib failure but carries a warning for Wernicke encephalopathy; pacritinib (PERSIST-2, approved 2022) is the option when platelets fall below 50 x 10^9/L; and momelotinib, which also blocks ACVR1 and so raises haemoglobin, was approved in 2023 after MOMENTUM, in which 25 percent of anaemic, previously treated patients had their symptom score halve against 9 percent on danazol, with more becoming transfusion independent. None of them clears the clone.

Allogeneic transplant is the only cure and is offered to fit patients with higher-risk disease (MIPSS70 high, typically under 70), with a JAK inhibitor to shrink the spleen beforehand; transplant-related mortality is substantial, and timing is the central clinical judgement. Anaemia is managed with momelotinib, erythropoietin, danazol, transfusion and, in trials, luspatercept (INDEPENDENCE). Combinations of ruxolitinib with navitoclax (TRANSFORM-1) or the BET inhibitor pelabresib (MANIFEST-2) roughly doubled spleen responses in phase 3 but have not yet reached approval, imetelstat is being tested against survival itself in IMpactMF, and interferon, selinexor and anti-fibrotic approaches are in trials; whether any drug changes the disease's course rather than its symptoms is the field's central question.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: PMF; Myelofibrosis; Chronic idiopathic myelofibrosis; Agnogenic myeloid metaplasia; Post-PV and post-ET myelofibrosis (secondary myelofibrosis)
- Tags: subtype-page
- Group: haematologic
- Burden: The rarest and most serious of the classic myeloproliferative neoplasms, about one new case per 100,000 people a year, mostly over 60; median survival is around six years but ranges from under two to more than fifteen depending on risk score.
- Subtypes: Prefibrotic primary myelofibrosis; Overt primary myelofibrosis, lower risk (DIPSS low or intermediate-1, MIPSS70 low); Overt primary myelofibrosis, higher risk (DIPSS intermediate-2 or high, MIPSS70 high; transplant candidates); Myelofibrosis with anaemia (momelotinib, luspatercept trials); Myelofibrosis with severe thrombocytopenia (pacritinib); Post-polycythaemia vera and post-essential thrombocythaemia myelofibrosis; Accelerated or blast phase myelofibrosis (MPN blast phase)
- Biomarkers: JAK2 V617F, CALR and MPL driver mutations (or triple negative); High-molecular-risk mutations: ASXL1, SRSF2, EZH2, IDH1/2, U2AF1; DIPSS-plus and MIPSS70-plus v2 scores; Marrow fibrosis grade; Spleen volume by imaging; Haemoglobin, platelet count and transfusion dependence; Blast percentage; Symptom score (MPN-SAF TSS)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/primary-myelofibrosis/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/primary-myelofibrosis/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/primary-myelofibrosis/#what-it-is [7 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/primary-myelofibrosis/#finding-it [8 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/primary-myelofibrosis/#treating-it [5 settings, 5 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/primary-myelofibrosis/#evidence [14 trials, 3 key papers, 8 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/primary-myelofibrosis/#science [8 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/primary-myelofibrosis/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/primary-myelofibrosis/#living-with-it [22 questions, 5 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/primary-myelofibrosis/coming/ [15 medicines, 14 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/primary-myelofibrosis/data/ [69 connected records]

## Standard of care

- Lower-risk, asymptomatic: Observation; aspirin for thrombosis risk where platelets are high; hydroxyurea or interferon for proliferative features. ([Aspirin](https://onco.cc/drugs/aspirin/), [Hydroxyurea (hydroxycarbamide)](https://onco.cc/drugs/hydroxyurea/), [Ropeginterferon alfa-2b](https://onco.cc/drugs/ropeginterferon-alfa-2b/), [Peginterferon alfa-2b](https://onco.cc/drugs/peginterferon-alfa-2b/))
- Symptomatic splenomegaly or constitutional symptoms: Ruxolitinib (COMFORT-I and II) first; fedratinib after ruxolitinib failure or intolerance; pacritinib if platelets are below 50 x 10^9/L; momelotinib if anaemic. ([Ruxolitinib](https://onco.cc/drugs/ruxolitinib/), [Fedratinib](https://onco.cc/drugs/fedratinib/), [Pacritinib](https://onco.cc/drugs/pacritinib/), [Momelotinib](https://onco.cc/drugs/momelotinib/), [COMFORT-I](https://onco.cc/trials/comfort-i/), [COMFORT-II](https://onco.cc/trials/comfort-ii/))
- Anaemia of myelofibrosis: Momelotinib (MOMENTUM), erythropoiesis-stimulating agents where erythropoietin is low, danazol, transfusion with iron chelation; luspatercept in trials (INDEPENDENCE). ([Momelotinib](https://onco.cc/drugs/momelotinib/), [Epoetin alfa](https://onco.cc/drugs/epoetin-alfa/), [Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/), [Luspatercept](https://onco.cc/drugs/luspatercept/), [An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomi](https://onco.cc/trials/nct04717414/), [Study of DISC-0974 (RALLY-MF) in Participants With Myelofibrosis or Myelodysplastic Syndrome and Anemia](https://onco.cc/trials/nct05320198/))
- Higher-risk, fit for transplant: Allogeneic stem cell transplant, usually under 70 and at MIPSS70 high or DIPSS intermediate-2 or higher, after JAK inhibitor to reduce spleen size. ([Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Ruxolitinib](https://onco.cc/drugs/ruxolitinib/), [Conditioning regimen (myeloablative, reduced-intensity)](https://onco.cc/terms/conditioning-regimen/))
- Ruxolitinib failure and trials: Switch JAK inhibitor; combination trials of ruxolitinib with navitoclax, pelabresib, selinexor or imetelstat; imetelstat versus best available therapy in IMpactMF. ([Navitoclax](https://onco.cc/drugs/navitoclax/), [Pelabresib](https://onco.cc/drugs/pelabresib/), [Selinexor](https://onco.cc/drugs/selinexor/), [Imetelstat](https://onco.cc/drugs/imetelstat/), [Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet Versus Best Available Therapy to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis](https://onco.cc/trials/nct04468984/), [Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis](https://onco.cc/trials/nct04562389/), [IMpactMF](https://onco.cc/trials/impactmf/), [Extended Access of Momelotinib in Adults With Myelofibrosis](https://onco.cc/trials/nct03441113/))

## State of the art

- Four approved JAK inhibitors cover the main clinical problems: spleen and symptoms (ruxolitinib, fedratinib), low platelets (pacritinib) and anaemia (momelotinib).
- Allogeneic transplant remains the only cure and the hardest decision, with mutation-based scores now guiding who and when.
- Combination phase 3 trials doubled spleen responses but have not yet shown disease modification or survival gain.

## Open problems

- No drug has been shown to change the course of the disease rather than its symptoms.
- Transplant timing: too early risks a fatal procedure in someone with years to live, too late loses the window.
- Blast phase myelofibrosis has no effective treatment.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Primary_myelofibrosis
- Wikipedia: https://en.wikipedia.org/wiki/Primary_myelofibrosis
- NCCN Guidelines: Myeloproliferative Neoplasms: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1477

## Connected records

- cancers: [Essential thrombocythaemia (ET)](https://onco.cc/cancers/essential-thrombocythaemia/), [Myeloproliferative neoplasms (PV, ET, myelofibrosis)](https://onco.cc/cancers/myeloproliferative-neoplasms/), [Polycythaemia vera (PV)](https://onco.cc/cancers/polycythaemia-vera/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/), [Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/)
- targets: [ACVR1 (ALK2)](https://onco.cc/targets/acvr1/), [BRD4](https://onco.cc/targets/brd4/), [CALR](https://onco.cc/targets/calr/), [JAK1](https://onco.cc/targets/jak1/), [JAK2](https://onco.cc/targets/jak2/)
- drugs: [Aspirin](https://onco.cc/drugs/aspirin/), [Danazol](https://onco.cc/drugs/danazol/), [Epoetin alfa](https://onco.cc/drugs/epoetin-alfa/), [Fedratinib](https://onco.cc/drugs/fedratinib/), [Hydroxyurea (hydroxycarbamide)](https://onco.cc/drugs/hydroxyurea/), [Imetelstat](https://onco.cc/drugs/imetelstat/), [Luspatercept](https://onco.cc/drugs/luspatercept/), [Momelotinib](https://onco.cc/drugs/momelotinib/), [Navitoclax](https://onco.cc/drugs/navitoclax/), [Pacritinib](https://onco.cc/drugs/pacritinib/), [Peginterferon alfa-2b](https://onco.cc/drugs/peginterferon-alfa-2b/), [Pelabresib](https://onco.cc/drugs/pelabresib/), [Ropeginterferon alfa-2b](https://onco.cc/drugs/ropeginterferon-alfa-2b/), [Ruxolitinib](https://onco.cc/drugs/ruxolitinib/), [Selinexor](https://onco.cc/drugs/selinexor/)
- terms: [Allogeneic stem cell transplant (allo-SCT)](https://onco.cc/terms/allogeneic-transplant/), [Anaemia](https://onco.cc/terms/anaemia/), [Conditioning regimen (myeloablative, reduced-intensity)](https://onco.cc/terms/conditioning-regimen/), [DIPSS, DIPSS-plus and MIPSS70 (myelofibrosis risk scores)](https://onco.cc/terms/dipss-mipss70/), [JAK2 V617F](https://onco.cc/terms/jak2-v617f/), [MPN driver mutations (JAK2 V617F, CALR, MPL) and allele burden](https://onco.cc/terms/mpn-driver-mutations/), [Post-PV myelofibrosis (spent phase)](https://onco.cc/terms/post-pv-myelofibrosis/)
- trials: [A Study of Low Dose Interferon Alpha Versus Hydroxyurea in Treatment of Chronic Myeloid Neoplasms](https://onco.cc/trials/nct01387763/), [A Study to Assess the Safety and Tolerability of BMS-986158 Alone and in Combination With Either Ruxolitinib or Fedratinib in Participants With Blood Cancer (Myelofibrosis)](https://onco.cc/trials/nct04817007/), [An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomi](https://onco.cc/trials/nct04717414/), [COMFORT-I](https://onco.cc/trials/comfort-i/), [COMFORT-II](https://onco.cc/trials/comfort-ii/), [Extended Access of Momelotinib in Adults With Myelofibrosis](https://onco.cc/trials/nct03441113/), [Fostamatinib as a Single Agent or in Combination With Ruxolitinib for Treatment of Patients With Myelofibrosis With Severe Thrombocytopenia](https://onco.cc/trials/nct04543279/), [IMpactMF](https://onco.cc/trials/impactmf/), [MANIFEST-2](https://onco.cc/trials/manifest-2/), [MOMENTUM](https://onco.cc/trials/momentum/), [P1101 in Treating Patients With Early PMF or Overt PMF at Low or Intermediate-1 Risk](https://onco.cc/trials/nct06468033/), [Study of DISC-0974 (RALLY-MF) in Participants With Myelofibrosis or Myelodysplastic Syndrome and Anemia](https://onco.cc/trials/nct05320198/), [Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet Versus Best Available Therapy to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis](https://onco.cc/trials/nct04468984/), [Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis](https://onco.cc/trials/nct04562389/)
- key papers: [COMFORT-I: ruxolitinib, the first JAK inhibitor, versus placebo for myelofibrosis](https://onco.cc/key-papers/paper-comfort-1-ruxolitinib-myelofibrosis-nejm-2012/), [COMFORT-II: JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis](https://onco.cc/key-papers/paper-comfort-ii-ruxolitinib-best-available-therapy-harrison-nejm-2012/), [MOMENTUM: momelotinib versus danazol for myelofibrosis patients with anaemia after a prior JAK inhibitor](https://onco.cc/key-papers/paper-momentum-momelotinib-lancet-2023/)
- people: [Raajit K. Rampal](https://onco.cc/people/raajit-rampal/), [Srdan Verstovsek](https://onco.cc/people/srdan-verstovsek/)

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JSON: https://onco.cc/api/v1/entities/primary-myelofibrosis.json