Primary Myelofibrosis

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN), which are a subset of bone marrow disorders. Primary myelofibrosis is a rare type of blood cancer characterized by bone marrow fibrosis, which impairs the production of normal blood cells. When myelofibrosis occurs on its own, it is called primary myelofibrosis, whereas secondary myelofibrosis (SMF) is when myelofibrosis occurs as a result of other diseases including MPNs such as polycythemia vera (PV) and essential thrombocythemia (ET).

The cause of myelofibrosis is unknown; however, researchers have discovered that these diseases can be caused by genetic mutations that affect proteins that work in signaling pathways of cells. There are a few risk factors associated with PMF, which include:

• Age: PMF is most commonly diagnosed in people over the age of 60
• Environment: exposure to certain chemicals, for example petrochemicals, can increase risk of developing PMF
• JAK2 Mutation: this mutation is found in 50-60 percent of people with PMF
• CALR Mutation: this mutation is found in approximately 24 percent of people with MF and ET

Primary Myelofibrosis Symptoms

In many cases, PMF is asymptomatic. PMF usually develops slowly, so as abnormal blood cell production increases, patients are more likely to experience symptoms such as:

• Feeling tired, weak, or short of breath due to anemia
• Pain or fullness below the ribs on the left side, due to an enlarged spleen
• Easy bruising
• Easy bleeding
• Excessive night-sweats
• Fever
• Bone pain
• Itching
• Susceptibility to infection

Primary Myelofibrosis Diagnosis

PMF varies greatly from person to person, so doctors have to review a wide variety of factors before they can diagnose PMF. The medical history, a physical exam, laboratory tests, and bone marrow exam are needed to diagnose the disease. Because symptoms are less common in PMF until later stages, signs doctors may notice include:

• An enlarged spleen (splenomegaly)
• Pale mucous membranes (pallor)
• Loss of muscle mass
• Cachexia (weight loss, muscle atrophy, weakness, and fatigue)

Common laboratory tests needed to diagnose PMF include:

• Blood tests
• Bone marrow biopsy
• Gene mutation analysis of blood cells (for JAK2, CALR, MPL mutations)
• Imaging tests

Primary Myelofibrosis Treatment

There is no specific standard treatment used for all PMF patients because each case varies greatly for each individual. Patients diagnosed with PMF who experience signs and symptoms are more likely to require treatment than those without them. Available treatments include:

• Jakafi (ruxolitinib) is the first drug that has been approved by the FDA to treat PMF. This treatment is recommended to patients with intermediate or high-risk cases of PMF. It is a checkpoint inhibitor drug which targets the JAK2 mutation, common in 50-60 percent of MF cases.
• Inebric (fedratinib) is a treatment available for adult patients with intermediate or high risk PMF or SMF. It is an oral kinase inhibitor that targets the JAK2 mutation.
• Allogenic Stem Cell Transplantation (ASCT) is considered to be the only curative treatment for MF. In this treatment, hematopoietic stem cells are transferred from a donor to a patient. This is not an option for all PMF patients.
• Clinical trials study novel therapies for treating PMF. The first approved drug for myelofibrosis, Jakafi (ruxolitinib), had to go through a clinical trial to get approved. Clinical trials are studying JAK inhibitor drugs, epigenetic drugs, pomalidomide, and everolimus.

It is important for PMF patients to consult with their doctor to understand which treatment is the best option for their unique cancer case.