New and Upcoming Treatment Options for Primary Myelofibrosis

The only curative therapy for primary myelofibrosis (PMF) is stem cell transplant, however, this therapy is recommended for high- and intermediate-risk patients only. Even in this group, age and other medical conditions can increase the risks associated with transplantation significantly making it a less than ideal therapy. Additionally, not all people with high- and intermediate-risk PMF will have a suitable stem cell transplant donor (matched sibling or matched unrelated donor). It is recommended that people with low-risk PMF receive treatment aimed at reducing symptoms associated with the disease.

Physician talking with patient in his office

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Perhaps your physician has advised that transplantation is not the best option for you, or no suitable donor can be identified, or you haven't tolerated other first-line therapies for PMF. Naturally, your next question might be—what other treatment options are available? Fortunately, there are many ongoing studies trying to find additional treatment options. We will review some of these medications briefly. 

JAK2 Inhibitors

Ruxolitinib, a JAK2 inhibitor, was the first targeted therapy identified for PMF. Mutations in the JAK2 gene have been associated with the development of PMF.

Ruxolitinib is an appropriate therapy for people with these mutations who cannot undergo stem cell transplantation. Fortunately, it has been found helpful even in people without JAK2 mutations. There is ongoing research looking to develop similar medications (other JAK2 inhibitors) that could be used in the treatment of PMF as well as combining ruxolitinib with other medications.

Momelotinib is another JAK2 inhibitor being studied for treatment of PMF. Early studies noted that 45% of people who received momelotinib had reduction in spleen size. About half of the people studied had improvement in their anemia and more than 50% were able to stop transfusion therapy. Thrombocytopenia (low platelet count) may develop and can limit effectiveness. Momelotinib will be compared to ruxolitinib in a phase 3 studies to determine its role in treatment for PMF. 

In August 2019, the FDA approved fedratinib for the treatment of adults with intermediate-2 or high-risk MF.

In February 2022, the FDA granted accelerated approval for Vonjo (pacritinib) to treat adults with intermediate or high-risk primary or secondary myelofibrosis with platelet (blood clotting cells) levels below 50,000/µL.

Immunomodulatory Drugs

Pomalidomide is an immunomodulatory drug (medications that alter the immune system). It is related to thalidomide and lenalidomide. In general, these medications are given with prednisone ( a steroid medication).

Thalidomide and lenalidomide have already been studied as treatment options in PMF. Although they both show benefit, their use is often limited by side effects. Pomalidomide was developed as a less toxic option. Some patients have improvement in anemia but no effect was seen in spleen size. Given this limited benefit, there are ongoing studies looking at combining pomalidomide with other agents like ruxolitinib for the treatment of PMF.

Epigenetic Drugs

Epigenetic drugs are medications that influence the expression of certain genes rather than physically changing them. One class of these medications are hypomethylating agents, which would include azacitidine and decitabine. These medications are currently used to treat myelodysplastic syndrome. Studies looking at the role of azacitidine and decitabine are in early phases. The other medications are histone deacetlyase (HDAC) inhibitors like givinostat and panobinostat.


Everolimus is a medication classified as an mTOR kinase inhibitor and immunosuppressant. It is FDA (Food and Drug Administration) approved for treatment of several cancers (breast, renal cell carcinoma, neuroendocrine tumors, etc.) and to prevent organ rejection in people who have received organ transplantation (liver or kidney). Everolimus is taken orally. Early studies indicate that it can decrease symptoms, spleen size, anemia, platelet count and white blood cell count.


Imetelstat has been studied in several cancers and myelofibrosis. In early studies, it has induced remission (deceased signs and symptoms of PMH) in some people with intermediate- or high-risk PMF.

If you don't respond to first-line treatment, enrolling in a clinical trial can give you access to novel therapies. Currently, there are more than 20 clinical trials assessing treatment options for people with myelofibrosis. You can discuss this option with your physician.

2 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Mullally, A., Hood, J, Harrison, C, et al. Fedratinib in myelofibrosis. Blood Adv (2020) 4 (8): 1792–1800. doi:10.1182/bloodadvances.2019000954

  2. Food and Drug Administration. FDA approves drug for adults with rare form of bone marrow disorder.

Additional Reading
  • Cervantes F. How I treat primary myelofibrosis. Blood. 2014;124:2635-2642.
  • Geyer HL and Mesa RA. Therapy for myeloproliferative neoplasms: when, which agent, and how? Blood. 2014;124:3529-3537.

By Amber Yates, MD
Amber Yates, MD, is a board-certified pediatric hematologist and a practicing physician at Baylor College of Medicine.