Medically reviewed by Dr. C.H. Weaver M.D. 8/2022
Myelofibrosis is a type of blood cancer known as a myeloproliferative neoplasm that is chronic and progressive in nature. It involves the abnormal development and function of bone marrow cells that produce blood cells and leads to the formation of scar tissue in the bone marrow. When the bone marrow becomes scarred it can’t make enough blood cells and this can cause anemia, enlargement of the spleen and liver, fatigue, and other problems. In some patients with myelofibrosis, the condition progresses to acute myeloid leukemia. Myelofibrosis is rare and affects ~ 18,000 people in the U. S. Although it can occur at any age it most commonly occurs in individuals over 65.
When myelofibrosis develops on its own (and not as the result of another bone marrow disease), it’s called primary myelofibrosis. Myelofibrosis can also result from a worsening of other bone marrow diseases, such as polycythemia vera and essential thrombocythemia.
The following is a general overview of the diagnosis and treatment of myelofibrosis. Recent advances in treatment have resulted in new treatment options that reduce symptoms and improve survival. Each person with myelofibrosis is different, and the specific characteristics of your condition will determine how it is managed. The information on this Web site is intended to help educate you about treatment options and to facilitate a shared decision-making process with your treating physician.1
Symptoms of Myelofibrosis
In its early stages, myelofibrosis may not cause any symptoms. As the disease progresses, patients may experience the following symptoms which are the result of an enlarged spleen, abnormal blood cell production, and the release of too many cytokines into the blood.1
Symptoms due to an enlarged spleen (spleenomegaly):
- Feeling pain or fullness below the ribs on the left side.
- Feeling full sooner than normal when eating.
- Pain under the left ribs.
Non-spleen related symptoms:
- Feeling very tired.
- Shortness of breath.
- Easy bruising or bleeding.
- Petechiae (flat, red, pinpoint spots under the skin that are caused by bleeding).
- Bone/muscle pain
- Night sweats.
- Weight loss.
These symptoms can have a profound impact on quality of life.
Diagnosis of Myelofibrosis
Individuals diagnosed with myelofibrosis often have no symptoms. An enlarged spleen or an abnormal blood count may be noticed at a routine check up. Once a diagnosis is suspected additional tests or procedures that may be used to diagnose primary myelofibrosis include blood tests and a bone marrow examination. People with primary myelofibrosis often have low red blood cell counts (anemia) in addition to other blood cell abnormalities.2
Roughly half of the people with primary myelofibrosis will test positive for a mutation in the Janus kinase 2 (JAK2) gene and the majority of individuals will have overactive JAK signaling even if the don’t have a JAK mutation. This abnormality can be measured by your doctor but doesn’t have to be present for a diagnosis. Increased production of JAK proteins causes the wrong number of blood cells and cytokines to be produced. An enlarged spleen may be detected on physical examination. Bone marrow examination typically reveals an increase in abnormal megakaryocytes (platelet-forming cells) and other abnormalities that are characteristic of myelofibrosis.
Slightly different criteria are used to diagnose myelofibrosis that develops after polycythemia vera or essential thrombocythemia.3
Treatment of Myelofibrosis
Several characteristics of the patient and the myelofibrosis are used to assess a patient’s prognosis and treatment needs.2 Risk factors associated with a worse prognosis include:
- Age over 65
- Night sweats, fever, unintended weight loss
- Higher than normal levels of white blood cells
- Higher than normal levels of immature (blast) blood cells
- Lower than normal levels of platelets
Commonly used scoring systems for primary myelofibrosis consider these and assign a patient to one of four risk groups: low risk, intermediate-1 risk, intermediate-2 risk, or high-risk. Patients with low-risk primary myelofibrosis have a median survival of more than 15-years, whereas median survival in the high-risk patients is less than two years.4
Depending on a patient’s individual situation, management of myelofibrosis may involve the following:
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Close observation: Patients who have a low or intermediate-1 risk status and no symptoms or complications from myelofibrosis may not require immediate treatment.
Drug treatment can help to manage the symptoms and complications of myelofibrosis. Three JAK inhibitors have been approved by the FDA: Jakafi (ruxolitinib), approved in November 2011; Inrebic(fedratinib), approved in August 2019; and Vonjo (pacritinib), granted accelerated approval in February 2022.1-6 Although these agents belong to the same medication class, they have distinguishing features that may help guide treatment selection.1-10
- Jakafi® (ruxolitinib) which has now been used for more than a decade, was the first treatment to receive FDA approval for patients with MF and has been demonstrated to improve long term survival, relieve the signs and symptoms of myelofibrosis, such as enlargement of the spleen, night sweats, itching, and bone or muscle pain, and improve quality of life.
Importantly, a recent study shows Jakafi® improves survival.
- Androgens: Drugs that contain male hormones such as testosterone may be used to treat anemia.
- Immunomodulators: drugs such as thalidomide or lenalidomide may also be used to treat anemia.
- Chemotherapy: drug such as hydroxyurea can reduce spleen size and help to relieve myelofibrosis symptoms.
- Corticosteroids: drugs such as prednisone can improve anemia in some patients.
Other drugs may also be used to manage symptoms and to reduce the occurrence or severity of complications from myelofibrosis.
- Vonjo (pacritinib) The FDA granted accelerated approval based on data from the phase 3 PERSIST-2 study which compared pacritinib with best available therapy (BAT) in patients with thrombocytopenia and primary or secondary MF. In patients with baseline platelet counts less than 50,000/ µL who received pacritinib 200 mg twice daily, 29% had at least 35% spleen volume reduction compared with 3% of patients receiving BAT.11
- Inrebic: Patients with myelofibrosis resistant or intolerant to Jakafi now have an alternative treatment option with a novel JAK2-selective inhibitor Inrebic (fedratinib).
Blood transfusions: Periodic blood transfusions may be necessary to manage anemia.
Splenectomy or radiation to the spleen: Surgical removal of the spleen (splenectomy) or radiation to the spleen may be necessary if drug treatment doesn’t adequately manage spleen size and blood counts.
Stem cell transplantation: For carefully selected patients with high- or intermediate-risk myelofibrosis, an allogeneic stem cell transplant (ASCT) may be an option. ASCT is the only potentially curative treatment for myelofibrosis, but can produce life-threatening side effects. The procedure involves high doses of chemotherapy or radiation to destroy the unhealthy bone marrow. Blood-forming stem cells from a healthy, matched donor are then infused into the patient. A reduced-intensity allogeneic stem cell transplant may also be an option for some patients. This procedure uses lower doses of chemotherapy or radiation.
Management of Myelofibrosis that Progresses to Acute Myeloid Leukemia
In some patients with myelofibrosis, the condition progresses to a type of leukemia known as acute myeloid leukemia (AML).
Information about the management of AML is available. Acute Myeloid Leukemia
Strategies to Improve Outcomes
The development of more effective treatment for myelofibrosis requires that new and innovative therapies be evaluated in MF patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Areas of active investigation aimed at improving the treatment of myelofibrosis include the following:
- Anemia Therapy Plus JAK Inhibition: A lack of anemia drugs is an unmet need within the field of myelofibrosis. Rebozyl (Luspatercept) may represent a potential solution and is being examined in combination with Jakafi.
- First-Line JAK Inhibitor Combinations: Several agents have shown promise in combination with Jakafi and are currently in clinical trials - the addition of navitoclax led to durable responses, at least 35% spleen volume reductions and significant reductions in symptoms but also was associated with significant improvements in hemoglobin levels and bone marrow fibrosis grade. In the phase 2 MANIFEST study investigators are examining the use of Pelabresib in combination with Jakafi.
- Novel Agents:
- Managing Very Low Platelet Counts
- National Cancer Institute: PDQ® Chronic Myeloproliferative Disorders Treatment. Bethesda, MD: National Cancer Institute. Date last modified 08/07/2013. Available here. Accessed 10/22/2013.
- Tefferi A. Primary myelofibrosis: 2013 update on diagnosis, risk-stratification, and management. American Journal of Hematology. 2013;88:142-150.
- Barosi G, Mesa RA, Thiele J et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: A consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia. 2008;22:437-438.
- Gangat N, Caramazza D, Vaidya R et al. DIPSS Plus: a refined dynamic international prognostic scoring system for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. Journal of Clinical Oncology. 2011;29:392-397.
- Mascarenhas J, Hoffman R. Ruxolitinib: the first FDA approved therapy for the treatment of myelofibrosis. Clin Cancer Res. 2012;18(11):30083014. doi:10.1158/1078-0432.CCR-11-3145
- FDA approves fedratinib for myelofibrosis. FDA. Updated August 16, 2019. Accessed March 28, 2022. bit.ly/3IFr1lK
- FDA approves drug for adults with rare form of bone marrow disorder. Updated March 1, 2022. Accessed March 28, 2022. bit.ly/3iFLQmq
- Jakafi. Prescribing information. Incyte; 2021. Accessed March 28, 2022. bit.ly/3uyiA6z
- Inrebic. Prescribing information. Celgene Corporation; 2021. Accessed March 28, 2022. bit.ly/35goXCW
- Vonjo. Prescribing information. CTI BioPharma Corp; 2022. Accessed March 28, 2022. bit.ly/3iGbEyG
- CTI BioPharma announces FDA accelerated approval of Vonjo (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. News release. CTI BioPharma Corp. February 28, 2022. Accessed March 29, 2022. bit.ly/3DGlSJ6