Primary myelofibrosis
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.
Overview
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, which is close to untreatable.
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.
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.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Check before combiningFood and drink: Selinexor
Nausea and anorexia are near-universal: prophylactic 5-HT3 antagonist plus olanzapine or dexamethasone.
- Check before combiningKidneys: Ruxolitinib
Reduce dose for CrCl below 60 with platelets under 150; dialysis dosing after each session.
- Good to knowAnaemia
A shortage of red blood cells or haemoglobin, causing tiredness and breathlessness. In cancer it comes from the disease itself (marrow infiltration, bleeding, inflammation), from chemotherapy suppressing the marrow, and from some targeted drugs.
- Good to knowAquagenic pruritus
Intense itching, prickling or burning of the skin within minutes of contact with water, typically after a shower. It affects a large minority of people with polycythaemia vera and can be the most disabling symptom.
- Good to knowErythromelalgia
Burning pain, redness and heat in the hands or feet, brought on by warmth. In polycythaemia vera and essential thrombocythaemia it comes from platelets clumping in tiny vessels and often disappears with low-dose aspirin.
See all on the product pages:AspirinImetelstatLuspaterceptRopeginterferon alfa-2bRuxolitinibSelinexor·Printable cards in the navigator
Anatomy and lymph node drainage
- Bone marrow (leukaemia, MDS, MPN, myeloma)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- Nodes: cervical
- Nodes: axillary
- Nodes: mediastinal
- Nodes: para-aortic and mesenteric
- Nodes: inguinal
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
- Bone marrow (leukaemia, MDS, MPN, myeloma)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)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- cervical
- axillary
- mediastinal
- para-aortic and mesenteric
- inguinal
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase
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.
- 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.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Observation; aspirin for thrombosis risk where platelets are high; hydroxyurea or interferon for proliferative features.
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.
Momelotinib (MOMENTUM), erythropoiesis-stimulating agents where erythropoietin is low, danazol, transfusion with iron chelation; luspatercept in trials (INDEPENDENCE).
Allogeneic stem cell transplant, usually under 70 and at MIPSS70 high or DIPSS intermediate-2 or higher, after JAK inhibitor to reduce spleen size.
Switch JAK inhibitor; combination trials of ruxolitinib with navitoclax, pelabresib, selinexor or imetelstat; imetelstat versus best available therapy in IMpactMF.
Subtypes & biomarkers
top- 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)
- 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)
How often this target appears
- 1879Heuck describes myelofibrosis
- 2005JAK2 V617F discovered in most polycythaemia vera and half of myelofibrosis
- 2011Ruxolitinib approved: the first JAK inhibitor, after COMFORT-I and II
- 2013CALR mutations found in most JAK2-negative myelofibrosis
- 2018MIPSS70 adds mutations to risk scoring for transplant decisions
- 2019Fedratinib approved after JAKARTA
- 2022Pacritinib approved for severe thrombocytopenia after PERSIST-2
- 2023Momelotinib approved for anaemic myelofibrosis after MOMENTUM
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 16 changes by month →- 2026-09-17This recordPrimary myelofibrosisFacts on this page last checked
When this page itself was last checked or edited.
- 2024ApprovalMomelotinibMomelotinib approved in EU
Myelofibrosis with moderate-to-severe anaemia
- 2023ApprovalMomelotinibMomelotinib approved in US
Intermediate/high-risk myelofibrosis with anaemia
- 2023MilestoneMomelotinibMomelotinib approved for anaemic myelofibrosis after MOMENTUM
A milestone in how this cancer is treated.
- 2022ApprovalPacritinibPacritinib approved in US
Intermediate/high-risk myelofibrosis with platelets <50×10⁹/L
- 2022MilestonePacritinibPacritinib approved for severe thrombocytopenia after PERSIST-2
A milestone in how this cancer is treated.
What is in development for Primary myelofibrosis, drawn from the whole corpus: 8 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Drugs in phase 3 · 2
Technologies being tested · 1
Trials under way · 5
- 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 · phase 3 · AbbVie
- An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomi · phase 3 · Celgene
- A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment · phase 3 · Geron Corporation
- Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis · phase 3 · Karyopharm Therapeutics Inc
- Extended Access of Momelotinib in Adults With Myelofibrosis · phase 2 · GlaxoSmithKline
Open problems and what is being done
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.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Indianapolis, IN · cancer center | United States | 0 | 159 | 4,238 | - | ||
Hamilton, ON · cancer center | Canada | none recorded | 0 | 103 | 1,158 | - | |
Baltimore, MD · cancer center | United States | 0 | 101 | 2,306 | - | ||
Omaha, NE · cancer center | United States | 0 | 37 | 4,159 | - | ||
Minneapolis, MN · cancer center | United States | 0 | not matched | - | - | ||
San Antonio, TX · cancer center | United States | 0 | not matched | - | none recorded | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Primary myelofibrosis but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Primary myelofibrosis
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, CALR and MPL driver mutations, High-molecular-risk mutations: ASXL1, SRSF2, EZH2, IDH1/2, U2AF1, DIPSS-plus and MIPSS70-plus v2 scores, Marrow fibrosis grade, Spleen volume by imaging), 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 Prefibrotic primary myelofibrosis, Overt primary myelofibrosis, lower risk, Overt primary myelofibrosis, higher risk.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Lower-risk, asymptomatic
- For my situation (lower-risk, asymptomatic), which of the standard options do you recommend and why?Why: Guideline options include: Observation; aspirin for thrombosis risk where platelets are high; hydroxyurea or interferon for proliferative features.
- Am I a candidate for Aspirin, Hydroxyurea (hydroxycarbamide), Ropeginterferon alfa-2b or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Symptomatic splenomegaly or constitutional symptoms
- For my situation (symptomatic splenomegaly or constitutional symptoms), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- 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 (MOMENTUM), erythropoiesis-stimulating agents where erythropoietin is low, danazol, transfusion with iron chelation; luspatercept in trials (INDEPENDENCE).
- Am I a candidate for Momelotinib, Epoetin alfa, Luspatercept, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomi and Study of DISC-0974 (RALLY-MF) in Participants With Myelofibrosis or Myelodysplastic Syndrome and Anemia apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Higher-risk, fit for transplant
- For my situation (higher-risk, fit for transplant), which of the standard options do you recommend and why?Why: Guideline options include: Allogeneic stem cell transplant, usually under 70 and at MIPSS70 high or DIPSS intermediate-2 or higher, after JAK inhibitor to reduce spleen size.
- Am I a candidate for Ruxolitinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Ruxolitinib failure and trials
- For my situation (ruxolitinib failure and trials), which of the standard options do you recommend and why?Why: Guideline options include: Switch JAK inhibitor; combination trials of ruxolitinib with navitoclax, pelabresib, selinexor or imetelstat; imetelstat versus best available therapy in IMpactMF.
- Am I a candidate for Navitoclax, Pelabresib, Selinexor or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of 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 and Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Momelotinib, Pacritinib, Navitoclax, Pelabresib?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 drug has been shown to change the course of the disease rather than its symptoms”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Transplant timing: too early risks a fatal procedure in someone with years to live, too late loses the window”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Primary myelofibrosis, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
6targets
4drugs
14companies
11terms
5trials
6key papers
2MOMENTUM 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.
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.
Latest papers
topQuery for this cancer: (TITLE:"Primary myelofibrosis" OR ABSTRACT:"Primary myelofibrosis" OR TITLE:"PMF" OR ABSTRACT:"PMF" OR TITLE:"Myelofibrosis" OR ABSTRACT:"Myelofibrosis" OR TITLE:"Chronic idiopathic myelofibrosis" OR ABSTRACT:"Chronic idiopathic myelofibrosis" OR TITLE:"Agnogenic myeloid metaplasia" OR ABSTRACT:"Agnogenic myeloid metaplasia" OR TITLE:"Post-PV and post-ET myelofibrosis secondary myelofibrosis" OR ABSTRACT:"Post-PV and post-ET myelofibrosis secondary myelofibrosis") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Primary myelofibrosis, not a curated reading list.
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